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Utility of the Functional Activities Questionnaire for Distinguishing Mild Cognitive Impairment From Very Mild Alzheimer Disease
Abstract
Current criteria for mild cognitive impairment (MCI) require "essentially intact" performance of activities of daily living (ADLs), which has proven difficult to operationalize. We sought to determine how well the Functional Activities Questionnaire (FAQ), a standardized assessment of instrumental ADLs, delineates the clinical distinction between MCI and very mild Alzheimer disease (AD). We identified 1801 individuals in the National Alzheimer's Coordinating Center Uniform Data Set with MCI (n=1108) or very mild AD (n=693) assessed with the FAQ and randomized them to the development or test sets. Receiver-operator curve (ROC) analysis of the development set identified optimal cut-points that maximized the sensitivity and specificity of FAQ measures for differentiating AD from MCI and were validated with the test set. ROC analysis of total FAQ scores in the development set produced an area under the curve of 0.903 and an optimal cut-point of 5/6, which yielded 80.3% sensitivity, 87.0% specificity, and 84.7% classification accuracy in the test set. Bill paying, tracking current events, and transportation (P's<0.005) were the FAQ items of greatest diagnostic utility. These data suggest that the FAQ exhibits adequate sensitivity and specificity when used as a standardized assessment of instrumental ADLs in the diagnosis of AD versus MCI.
... RBANS was not administered to participants with an MMSEscore ≤ 20 who were classified as having 'cognitive impairment' . The FAQ cutoff score of 5/6 was based on a large validation study including participants with MCI and mild Alzheimer's disease [20]. ...
... Further summary results regarding cognitive performance in four separate age groups are presented in Supplementary Table S2. The median time between the first research visit (assessment with BASIC-Q) and the second research visit (extended assessment) was 29.5 days (interquartile range [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. The 'normal cognition' group (n = 154) was significantly younger than the 'cognitive impairment' group (n = 101) (t (253) = -4.21, ...
Objectives
This study aims to evaluate the diagnostic accuracy and reliability of a new, brief questionnaire, ‘Brief Assessment of Impaired Cognition– Questionnaire’ (BASIC-Q) for detection of cognitive impairment, primarily developed for use in primary care. BASIC-Q has three components: Self-report, Informant report, and Orientation. Self-report and Orientation are completed by the individual and Informant report is answered by a close relative.
Methods
We included 275 participants ≥ 70 years, without a prior diagnosis of dementia, and with a close relative who agreed to participate as an informant. Participants were included prospectively in 14 general practices in urban and rural Denmark using a convenience sampling method. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the informant-completed Functional Activities Questionnaire (FAQ) and reported memory concern were used as a reference standard for the classification of the participants’ cognitive function.
Results
BASIC-Q demonstrated a fair to good diagnostic accuracy to differentiate between people with cognitive impairment and normal cognition with an area under the ROC curve (AUC) of 0.84 (95% CI 0.79–0.89) and a sensitivity and specificity of 0.80 (95% CI 0.72–0.87) and 0.71 (95% CI 0.63–0.78). A prorated BASIC-Q score derived from BASIC-Q without Informant report had significantly lower classification accuracy than the full BASIC-Q. The test-retest reliability of BASIC-Q was good with an intraclass correlation coefficient of 0.84.
Conclusion
BASIC-Q is a brief, easy-to-use questionnaire for identification of cognitive impairment in older adults. It demonstrated fair to good classification accuracy in a general practice setting and can be a useful case-finding tool when suspecting dementia in primary health care.
... Neuropsychological assessments such as the FAQ, the ADAS-Cog-13, Mini Mental State Examination (MMSE) and others [8][9][10], are useful methods that can screen for signs of early cognitive impairment. These assessments are usually quicker, easier to carry out when compared with pathological procedures and show good performance with reference to validity, sensitivity, and specificity [11,12]. However, little research works have been conducted on measuring the progression of AD using cognitive features, i.e., [6,7,13]. ...
... To measure the performance of the AD progression models derived by the classifiers against the subsets of cognitive features a number of standard evaluation metrics in machine learning including predictive accuracy, sensitivity, and the specificity [12,22] were utilised. Sensitivity is the measure of the proportion of actual positive cases that got predicted as positive. ...
Prognosis of Alzheimer’s disease (AD) progression has been recognized as a challenging problem due to the massive numbers of cognitive, and pathological features recorded for patients and controls. While there have been many studies investigated the diagnosis of dementia using pathological characteristics, predicting the advancement of the disease using cognitive elements has not been heavily studied particularly using technologies like artificial intelligence and machine learning. This research aims at evaluating items of the Alzheimer’s Disease Assessment Scale-Cognitive 13 (ADAS-Cog-13) test to determine key cognitive items that influence the progression of AD. A methodology that consists of machine learning and feature selection (FS) techniques was designed, implemented, and then tested against real data observations (cases and controls) of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) repository with a narrow scope on cognitive items of the ADAS-Cog-13 test. Results obtained by ten-fold cross validation and using dissimilar classification and FS techniques revealed that the decision tree algorithm produced classification models with the best performing results from the cognitive items. For ADAS-Cog-13 test, memory and learning features including word recall, delayed word recall and word recognition were the key items pinpointing to AD advancement. When these three cognitive items are processed excluding demographics by C4.5 algorithm the models derived showed 82.90% accuracy, 87.60% sensitivity and 78.20% specificity.
... Neuropsychological assessments such as the FAQ, the ADAS-Cog-13, Mini Mental State Examination (MMSE) and others [8][9][10], are useful methods that can screen for signs of early cognitive impairment. These assessments are usually quicker, easier to carry out when compared with pathological procedures and show good performance with reference to validity, sensitivity, and specificity [11,12]. However, little research works have been conducted on measuring the progression of AD using cognitive features, i.e., [6,7,13]. ...
... To measure the performance of the AD progression models derived by the classifiers against the subsets of cognitive features a number of standard evaluation metrics in machine learning including predictive accuracy, sensitivity, and the specificity [12,22] were utilised. Sensitivity is the measure of the proportion of actual positive cases that got predicted as positive. ...
Prognosis of Alzheimer’s disease (AD) progression has been recognized as a challenging problem due to the massive numbers of cognitive, and pathological features recorded for patients and controls. While there have been many studies investigated the diagnosis of dementia using pathological characteristics, predicting the advancement of the disease using cognitive elements has not been heavily studied particularly using technologies like artificial intelligence and machine learning. This research aims at evaluating items of the Alzheimer’s Disease Assessment Scale-Cognitive 13 (ADAS-Cog-13) test to determine key cognitive items that influence the progression of AD. A methodology that consists of machine learning and feature selection (FS) techniques was designed, implemented, and then tested against real data observations (cases and controls) of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) repository with a narrow scope on cognitive items of the ADAS-Cog-13 test. Results obtained by ten-fold cross validation and using dissimilar classification and FS techniques revealed that the decision tree algorithm produced classification models with the best performing results from the cognitive items. For ADAS-Cog-13 test, memory and learning features including word recall, delayed word recall and word recognition were the key items pinpointing to AD advancement. When these three cognitive items are processed excluding demographics by C4.5 algorithm the models derived showed 82.90% accuracy, 87.60% sensitivity and 78.20% specificity.
... (i) Participants with AD aMCI (n = 33) met the clinical criteria for aMCI (Albert et al., 2011) including memory complaints, evidence of memory impairment [i.e., score lower than 1.5 standard deviations (SDs) below the age-and education-adjusted norms in any memory test], generally intact instrumental activities of daily living [<6 points on the Functional Activities Questionnaire, Czech Version (FAQ-CZ); Teng et al., 2010;Bezdíček et al., 2011] and absence of dementia. The participants had positive CSF AD biomarkers (reduced amyloid-β 1-42 and elevated p-tau 181 (<665 pg/ml and >48 pg/ml, respectively, the internally validated cut-offs; Parizkova et al., 2018;Laczó et al., 2021b;n = 9), positive amyloid PET imaging (positive visual read of 18F-flutemetamol PET scan; n = 16), or both, positive CSF AD biomarkers and amyloid PET imaging (n = 8). ...
... (iii) Participants with mild AD dementia (n = 28) met the clinical criteria for dementia (Mckhann et al., 2011) with evidence of progressive cognitive impairment in at least two cognitive domains including memory (i.e., score lower than 1.5 SDs below the age-and education adjusted norms in any memory test and in at least one other non-memory cognitive test) and significant impairment in instrumental activities of daily living (≥6 points on the FAQ-CZ; Teng et al., 2010;Bezdíček et al., 2011). The participants had positive CSF AD biomarkers [reduced amyloid-β 1-42 (<665 pg/ml) and elevated p-tau 181 (>48 pg/ml; Parizkova et al., 2018;Laczó et al., 2021b) n = 14], positive amyloid PET imaging (n = 10), or both, positive CSF AD biomarkers and amyloid PET imaging (n = 4). ...
Background
Spatial navigation impairment is a promising cognitive marker of Alzheimer’s disease (AD) that can reflect the underlying pathology.
Objectives
We assessed spatial navigation performance in AD biomarker positive older adults with amnestic mild cognitive impairment (AD aMCI) vs. those AD biomarker negative (non-AD aMCI), and examined associations between navigation performance, MRI measures of brain atrophy, and cerebrospinal fluid (CSF) biomarkers.
Methods
A total of 122 participants with AD aMCI ( n = 33), non-AD aMCI ( n = 31), mild AD dementia ( n = 28), and 30 cognitively normal older adults (CN) underwent cognitive assessment, brain MRI ( n = 100 had high-quality images for volumetric analysis) and three virtual navigation tasks focused on route learning (body-centered navigation), wayfinding (world-centered navigation) and perspective taking/wayfinding. Cognitively impaired participants underwent CSF biomarker assessment [amyloid-β 1–42 , total tau, and phosphorylated tau 181 (p-tau 181 )] and amyloid PET imaging ( n = 47 and n = 45, respectively), with a subset having both ( n = 19).
Results
In route learning, AD aMCI performed worse than non-AD aMCI ( p < 0.001), who performed similarly to CN. In wayfinding, aMCI participants performed worse than CN (both p ≤ 0.009) and AD aMCI performed worse than non-AD aMCI in the second task session ( p = 0.032). In perspective taking/wayfinding, aMCI participants performed worse than CN (both p ≤ 0.001). AD aMCI and non-AD aMCI did not differ in conventional cognitive tests. Route learning was associated with parietal thickness and amyloid-β 1–42 , wayfinding was associated with posterior medial temporal lobe (MTL) volume and p-tau 181 and perspective taking/wayfinding was correlated with MRI measures of several brain regions and all CSF biomarkers.
Conclusion
AD biomarker positive and negative older adults with aMCI had different profiles of spatial navigation deficits that were associated with posterior MTL and parietal atrophy and reflected AD pathology.
... A neuropsychological z-score was considered reflective of impairment if it fell more than one standard deviation below the corresponding adjusted normative mean. FAQ scores of 6 or higher were considered indicative of significant functional impairment in differentiating between MCI and dementia (Teng et al., 2010). ...
... In the NHB subsample, similar patterns were observed, although with some exceptions (i.e. the impaired-not-MCI group was comparable to both the CN and MCI groups on FAQ scores, and to the CN group on CDR-SB scores; refer to Figure 3). These findings extend those of previous studies demonstrating the FAQ's ability to discriminate between CN, MCI, and dementia stages (Brown et al., 2011;Pfeffer et al., 1982;Teng et al., 2010) by highlighting that both the FAQ and the CDR-SB index are able to discriminate between CN, MCI, and dementia stages in both NHB and NHW samples. Additionally, while ratings of functioning were significantly lower, on average, for NHB participants than for NHW participants, this effect was small, and appeared to be driven by racial group differences on reported functioning among participants with MCI in particular. ...
Objective
We recently demonstrated that relative to consensus-based methods, actuarial methods may improve diagnostic accuracy across the continuum of cognitively normal (CN), mild cognitive impairment (MCI), and dementia in the overall National Alzheimer’s Coordinating Center (NACC) cohort. However, the generalizability and comparative utility of current methods of diagnosing MCI and dementia due to Alzheimer’s disease and related disorders (ADRD) are significantly understudied in non-Hispanic Black (NHB) older adults. Thus, we extended our previous investigation to more specifically explore the utility of consensus-based and actuarial diagnostic methods in NHB older adults.Method: We compared baseline consensus and actuarial diagnostic rates, and associations of ratings of functioning with neuropsychological performance and diagnostic outcomes, in NHB (n = 963) and non-Hispanic White (NHW; n = 4577) older adults in the NACC cohort.Results: 60.0% of the NHB subsample, versus 29.2% of the NHW subsample, included participants who met actuarial criteria for MCI despite being classified as CN or impaired-not-MCI per consensus. Additionally, associations between ratings of functioning and neuropsychological performance were less consistent in NHB participants than in NHW participants.Conclusions: Our results provide evidence of differential degrees of association between reported functioning and neuropsychological performance in NHB and NHW older adults, which may contribute to racial group differences in diagnostic rates, and prompt consideration of the strengths and weaknesses of consensus-based and actuarial diagnostic approaches in assessing neurocognitive functioning in NHB older adults.
... Among these measures, Pfeffer's Functional Activities Questionnaire (FAQ; Pfeffer et al., 1982) is one of the most frequently utilized and serves as the primary ADL measure for large aging-related databases such as the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (Besser et al., 2018). Prior research with the NACC sample and FAQ has found the measure to have attractive measurement properties in older adult samples (González et al., 2021(González et al., , 2022Teng et al., 2010), including lack of item bias among subgroups of race, ethnicity, sex, and educational attainment . ...
Objective: To evaluate the extent to which demographic factors—and their intersections—influence the applicability of items assessing activities of daily living (ADLs) in a sample of older adults. Method: Participants’ (n = 44,713) Functional Activities Questionnaire (FAQ) scores from a multicenter database were evaluated to see how participant and collateral demographics, contextual, and clinical characteristics impacted ADL nonapplicability (NA). Collateral, contextual, and clinical characteristics were matched in those with and without NA. The effect of participant demographics and their interactions on NA responses were modeled with logistic regression. Results: At least one FAQ item (most commonly bill payment, taxes, playing games, and meal preparation) was rated as NA in up to one third of participants across ethnoracial groups. Dementia staging had the largest impact on NA, followed by participant demographics. In a matched sample, logistic models revealed that participant demographics, in particular sex, best predicted NA. However, meaningful interactions with ethnoracial group were noted for bill payment, taxes, meal preparation, and game engagement, suggesting that demographic intersections (e.g., younger vs. older Latinxs) meaningfully predict whether a given ADL was applicable to an individual participant. Conclusions: Neuropsychology is predicated on accurate assessments of both cognition and daily functioning and, in an increasingly diverse aging population, there should be careful consideration of demographic factors, their interactions, and historical contexts that drive day-to-day demands. This study establishes limitations of existing measures and paths forward for creating fair measures of functioning in older adults.
... Some of these activities are: eating, showering, shopping, dressing, using public transport. Functional Activities Questionnaire (FAQ) is an example of test specialized in this domain [66,67]. Others are Katz's index [68], Barthel's index [69], and Lawton-Brody's index [70]. ...
Background: The growing number of older adults in recent decades has led to more prevalent geriatric diseases, such as strokes and dementia. Therefore, Alzheimer’s disease (AD), as the most common type of dementia, has become more frequent too. Background: Objective: The goals of this work are to present state-of-the-art studies focused on the automatic diagnosis and prognosis of AD and its early stages, mainly mild cognitive impairment, and predicting how the research on this topic may change in the future. Methods: Articles found in the existing literature needed to fulfill several selection criteria. Among others, their classification methods were based on artificial neural networks (ANNs), including deep learning, and data not from brain signals or neuroimaging techniques were used. Considering our selection criteria, 42 articles published in the last decade were finally selected. Results: The most medically significant results are shown. Similar quantities of articles based on shallow and deep ANNs were found. Recurrent neural networks and transformers were common with speech or in longitudinal studies. Convolutional neural networks (CNNs) were popular with gait or combined with others in modular approaches. Above one third of the cross-sectional studies utilized multimodal data. Non-public datasets were frequently used in cross-sectional studies, whereas the opposite in longitudinal ones. The most popular databases were indicated, which will be helpful for future researchers in this field. Conclusions: The introduction of CNNs in the last decade and their superb results with neuroimaging data did not negatively affect the usage of other modalities. In fact, new ones emerged.
... When a questionnaire aims to recognise the presence/absence of certain symptoms or features that are representative of specific populations, it is common to measure them with dichotomous items (Ising et al., 2012;Teng et al., 2010). We used BNs and the JSDd to analyse dichotomous items and, in particular, as an item selection technique for binary classification. ...
The validation of questionnaires, crucial for discriminating between diverse populations, is a standard practice in psychology and medicine. While latent factor models have conventionally dominated psychometric questionnaire validation, recent developments have introduced alternative method-ologies such as Network Analysis. This study presents a pioneering approach that integrates information theory, machine learning (ML), and Bayesian networks (BNs) into questionnaire validation. This novel perspective shifts the emphasis from latent factors to individual items. We used the Jensen-Shannon Divergence (JSDd) for item selection, employing three machine learning algorithms (Decision Trees, Random Forests, and Support Vector Machines with a linear kernel) to identify the items with optimal discriminative power. The selection process balanced the number of items against model accuracy in a data-driven manner. Bayesian Networks (BNs) were employed to uncover conditional dependences between items, offering insights into the complex systems underlying the psychological construct. We validated the proposed method on two simulated data sets, one with dichotomous and the other with Likert-scale data. Results show the efficacy of the proposed method in identifying the most discriminative items, thereby enhancing the instrument's discriminative power. Simultaneously, it mitigated respondent burden by minimising the required number of administered items and providing insights into the criterion validity, content validity, and construct validity of the instrument.
... FAQ is a collateral-report scale that evaluates instrumental activities of daily living [50], and it can differentiate MCI from AD given that functional changes are found early in dementia patients. In particular, Teng et al. [71] demonstrated the prognosis utility of FAQ, showing that it exhibits optimal accuracy (84.7%), sensitivity (80.3%) and specificity (87.0%) in discriminating MCI patients from very mild AD patients. In the present study, FAQ was the most important clinical scale in local explanation on test set (mean |SHAP| value + 0.15, Fig. 3B), and among the first eight features in global explanations (Fig. 2). ...
Random Survival Forests (RSF) has recently showed better performance than statistical survival methods as Cox proportional hazard (CPH) in predicting conversion risk from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). However, RSF application in real-world clinical setting is still limited due to its black-box nature.
For this reason, we aimed at providing a comprehensive study of RSF explainability with SHapley Additive exPlanations (SHAP) on biomarkers of stable and progressive patients (sMCI and pMCI) from Alzheimer’s Disease Neuroimaging Initiative. We evaluated three global explanations—RSF feature importance, permutation importance and SHAP importance—and we quantitatively compared them with Rank-Biased Overlap (RBO). Moreover, we assessed whether multicollinearity among variables may perturb SHAP outcome. Lastly, we stratified pMCI test patients in high, medium and low risk grade, to investigate individual SHAP explanation of one pMCI patient per risk group.
We confirmed that RSF had higher accuracy (0.890) than CPH (0.819), and its stability and robustness was demonstrated by high overlap (RBO > 90%) between feature rankings within first eight features. SHAP local explanations with and without correlated variables had no substantial difference, showing that multicollinearity did not alter the model. FDG, ABETA42 and HCI were the first important features in global explanations, with the highest contribution also in local explanation. FAQ, mPACCdigit, mPACCtrailsB and RAVLT immediate had the highest influence among all clinical and neuropsychological assessments in increasing progression risk, as particularly evident in pMCI patients’ individual explanation. In conclusion, our findings suggest that RSF represents a useful tool to support clinicians in estimating conversion-to-AD risk and that SHAP explainer boosts its clinical utility with intelligible and interpretable individual outcomes that highlights key features associated with AD prognosis.
Graphical Abstract
... This study included dementia severity measures (dementia severity rating scale-DSRS and functional assessment questionnaire-FAQ). The DSRS is a brief informant-rated, multiple-choice questionnaire made up of 12-items that measure functional abilities in persons with cognitive disorders (score 0-18 mild; 19-36 moderate; 37-54 severe) [7] whereas the FAQ is a brief subjective assessment of instrumental activities of daily that is typically completed by the caregiver with scores ≥9 suggestive of dementia [8,9]. ...
Background and objectives
The University of California, San Francisco Memory and Aging Center (UCSF-MAC) led the development and tested a collaborative care model delivered by lay care team navigators (CTNs) with support from a multidisciplinary team known as the Care Ecosystem (CE). We evaluated outcomes related to the feasibility of the CE in a non-academic healthcare system, including acceptability, adoption, and fidelity to the original UCSF model.
Research Design and methods
The CE team at HealthPartners consisted of two CTNs, a social worker, an RN, a program coordinator, and a behavioral neurologist. Intake forms were developed to collect demographic, baseline, and annual data at one year related to dementia severity and caregiver status. Experience surveys were completed at 6 and 12 months by participating caregivers. All data was entered into REDCap.
Results
A total of 570 PWD-caregiver dyads were recruited into the CE: 53% PWDs female, average age 75.2 ± 9.43, 19% living within rural communities. Of the 173 dyads assessed at one year, 30% responded to the annual intake forms and 58% of responded to experience surveys. At one year, PWDs progressed in disease severity and functional impairment, although caregiver burden and mood remained unchanged. We observed a significant reduction in caregiver reported emotional challenges associated with caregiving, sleep problems, and obtaining caregiver help at one year. 86% of caregivers reported feeling supported by their CTN nearly always or quite frequently, and 88% rated the CTN as highly responsive to what was important to them.
Discussion and implications
The CE was feasible and well-received within a non-academic healthcare system.
... Prior literature supports the reliability and validity of the FAQ as a measure of daily functioning in the UDS sample and in non-UDS, demographically diverse samples Tappen et al., 2010). Further, the FAQ demonstrates strong classification accuracy when differentiating normal cognition, mild cognitive impairment, and dementia Teng et al., 2010;Yin et al., 2020). ...
Objectives:
Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB.
Methods:
The study sample included 97 participants with consensus-defined DLB from the National Alzheimer's Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual's performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual's performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ).
Results:
Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores).
Conclusions:
Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.
... (8) attending to and understanding a television program, book, or magazine; (9) remembering appointments, family occasions, medications; and (10) traveling out of the neighborhood. 37 In NACC-UDS, approximately 75% of informants were children or spouses of the participants. ...
Introduction:
Efforts to harmonize measures of everyday function and dementia-related behaviors are needed to synthesize across studies in dementia research. There have been some psychometric attempts to harmonize everyday function for secondary analysis, but far less for dementia-related behaviors.
Methods:
Statistical co-calibration was performed to generate factor scores representing everyday function and dementia-related behaviors for participants with dementia. We evaluated convergent criterion validity of factor scores and mapped the scores onto established clinical instruments.
Results:
Factor analyses of included items fit well to available data. Harmonized factors showed expected associations with the Global Clinical Dementia Rating (CDR) score, with greater impairment (higher Global CDR score) corresponding to higher (more severe) levels on factor scores.
Discussion:
We used large, well-characterized samples to derive harmonized factors representing everyday functions and dementia-related behaviors. These harmonized factors can be used to tackle questions about dementia phenotypes which require either large samples or unique subpopulations.
... Eligible participants were adults aged 35-75 years, fluent in English, and residents of Marion County with an HTN diagnosis, last systolic blood pressure ≥120 mm Hg, Hunger Vital Sign diagnosis of food insecure, and food insecurity score ≥2 on the 18-item United States Department of Agriculture (USDA) Household Food Security Survey Module (HFSSM), indicating low or very low food security over the past 30 days [19,[36][37][38]. Additionally, participants must have self-reported stable housing, independent access to a kitchen with a functional stove or hotplate, refrigerator and freezer, activity independence per functional activities questionnaire [39,40], normal cognition per six-item screener [41], and willingness to provide blood samples, use a touchscreen device, and participate via live video telehealth conferencing. ...
Food insecurity affects nearly 50 million Americans and is linked to cardiovascular disease risk factors and health disparities. The purpose of this single-arm pilot study was to determine the feasibility of a 16-week dietitian-led lifestyle intervention to concurrently address food access, nutrition literacy, cooking skills, and hypertension among safety-net primary care adult patients. The Food Resources and Kitchen Skills (FoRKS) intervention provided nutrition education and support for hypertension self-management, group kitchen skills and cooking classes from a health center teaching kitchen, medically tailored home-delivered meals and meal kits, and a kitchen toolkit. Feasibility and process measures included class attendance rates and satisfaction and social support and self-efficacy toward healthy food behaviors. Outcome measures included food security, blood pressure, diet quality, and weight. Participants (n = 13) were on average {mean (SD)} aged 58.9 ± 4.5 years, 10 were female, and 12 were Black or African American. Attendance averaged 19 of 22 (87.1%) classes and satisfaction was rated as high. Food self-efficacy and food security improved, and blood pressure and weight declined. FoRKS is a promising intervention that warrants further evaluation for its potential to reduce cardiovascular disease risk factors among adults with food insecurity and hypertension.
... It should be noted that cognitive tests such as The FAQ is a commonly used IADL scale that has been shown in one study to offer adequate sensitivity to distinguish between MCI and mild AD dementia. 41 Battery. 43,44 It should be noted again that a major caveat for the use of these scales is that they were developed, validated, and standardized in groups of Western white people and may not apply to other groups and cultures. ...
... The Functional Assessment Questionnaire, a measure of independence that correlates with cognitive status and helps distinguish mild cognitive impairment from mild dementia, was administered to each participant. (23) If available, participants' care partners were invited to participate in the study. The researchers had no prior relationships with any of the participants (Table 1). ...
Background:
Person-centred care is at the core of high-quality dementia care but people living with dementia are often excluded from quality improvement efforts. We sought to explore person-centred care and quality of care from the perspectives of persons living with dementia in the community and their care partners.
Methods:
We used a qualitative descriptive approach with in-person, semi-structured interviews with 17 participants (9 persons living with dementia and 8 care partners) from Ontario, Canada.
Results:
Participants report that person-centred care is essential to the quality of dementia care. Three themes were identified that describe connections between person-centred care and quality of care: 1) "I hope that the people looking after me know about me", 2) "I just like to understand [what's happening] as we go down the road", and 3) "But the doctor doesn't even know all the resources that are available." Participants perceived that quality indicators over-emphasized technical/medical aspects of care and do not entirely capture quality of care.
Conclusions:
Persons living with dementia and their care partners provide important insights into person-centredness and quality of care. Their perspectives on "quality" may differ from clinicians and researchers. Research is needed to better integrate their perspectives in quality improvement and person-centred care.
... In our study participants with higher disability were more likely to report SMD irrespective of their cognitive impairment. Nevertheless, IADL seem fairly preserved in older adults with subjective cognitive complaints (65). This may suggest a preserved independence despite difficulties in daily functioning. ...
Background
Subjective cognitive decline (SCD) and subjective memory decline (SMD) are common among older people. Evidence linking SCD and SMD with cognitive and memory impairment is inconsistent. Moreover, little is known about the associations of SCD and SMD with disability. We aimed to explore the associations of SCD and SMD with objective cognitive and memory performance, disability, and depressive symptoms.
Materials and methods
In a cross-sectional study we conducted face to face interviews in a randomized sample of people aged ≥65 years living in the Canton of Ticino, southern Switzerland, between May 2021 and April 2022. We measured subjective cognitive decline with the MyCog, a subsection of the Subjective Cognitive Decline Questionnaire (SCD-Q); cognitive functioning with the Community Screening Instrument for Dementia; memory with the consortium to establish a registry for alzheimer’s disease (CERAD) 10-word list learning task; and disability and depressive symptoms with the world health organization disability assessment schedule 2.0 (WHO-DAS 2.0) and the Euro-Depression (EURO-D) scales, respectively.
Results
Of the 250 participants 93.6% reported at least one cognitive difficulty, and 40.0% SMD. Both SCD and SMD were associated with poorer objective cognitive/memory performance, and independently with greater disability, and more depressive symptoms. But in participants with high disability and depressive symptoms subjective and objective cognition were no longer associated. Disability fully mediated the associations of poorer objective cognitive and memory performance with subjective cognitive and memory decline.
Conclusion
Routine clinical assessments of cognitive function should include formal enquires about SCD and SMD, and also account for disability and depressive symptoms.
... We used the dataset generated by [7] for our feature selection. [13], Alzheimer's Disease Assessment Scale (ADAS) [2], Functional Activities Questionnaire (FAQ) [14], Everyday Cognition -Patient scale [15], Geriatric Depression Scale [16], and Neuropsychological Battery (NB) and used multiple methods of feature selection to generate a set of 35 sub-features which were frequently selected, and assigned time costs in seconds to these subfeatures [7]. In this dataset, Clinical Dementia Rating Sum-of-Boxes (CDR-SB) rating was used as a measure of dementia severity [7]. ...
Current machine learning techniques for dementia diagnosis often do not take into account real-world practical constraints, which may include, for example, the cost of diagnostic assessment time and financial budgets. In this work, we built on previous cost-sensitive feature selection approaches by generalising to multiple cost types, while taking into consideration that stakeholders attempting to optimise the dementia care pathway might face multiple non-fungible budget constraints. Our new optimisation algorithm involved the searching of cost-weighting hyperparameters while constrained by total budgets. We then provided a proof of concept using both assessment time cost and financial budget cost. We showed that budget constraints could control the feature selection process in an intuitive and practical manner, while adjusting the hyperparameter increased the range of solutions selected by feature selection. We further showed that our budget-constrained cost optimisation framework could be implemented in a user-friendly graphical user interface sandbox tool to encourage non-technical users and stakeholders to adopt and to further explore and audit the model - a humans-in-the-loop approach. Overall, we suggest that setting budget constraints initially and then fine tuning the cost-weighting hyperparameters can be an effective way to perform feature selection where multiple cost constraints exist, which will in turn lead to more realistic optimising and redesigning of dementia diagnostic assessments. Clinical Relevance-By optimising diagnostic accuracy against various costs (e.g. assessment administration time and financial budget) predictive yet practical dementia diagnostic assessments can be redesigned to suit clinical use.
... Instrumental activities of daily living (IADL), such as driving, shopping, and managing finances or medications (Gold, 2012), recruit multiple cognitive domains and require planning and cognitive flexibility to complete (Mitchell and Miller, 2008). IADL is mostly preserved in Mild Cognitive Impairment (MCI) (Teng et al., 2010) but becomes impaired to varying degrees in mild dementia. The reliable and accurate assessment of IADL in an individual with cognitive deficits is therefore critical for determining a dementia diagnosis. ...
Objective
Previous research shows that depression and personality are independently associated with self- and informant-reports of the ability to perform instrumental activities of daily living (IADLs). However, less is known about the association between depression and personality and performance-based measures of IADLs. We aimed to determine how depression and personality predict self-and informant-reports of IADL compared to performance-based measures of IADLs in a sample of older adults with normal cognition (NC) and Mild Cognitive Impairment (MCI).
Methods
Participants consisted of 385 older adults with NC ( n = 235), or a diagnosis of MCI ( n = 150), aged between 76 and 99-years from the Sydney Memory and Ageing Study. Participants underwent comprehensive neuropsychological and clinical assessments to determine global cognition and clinical diagnoses. Personality traits were measured by the NEO Five-Factor Inventory (NEO-FFI) and depression by the Geriatric Depression Scale (GDS). Subjective IADLs were self- and informant-reported Bayer Activities of Daily Living (B-ADL) scales and objective IADL was the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). Linear regressions examined the relationship between depression and personality and the three types of IADL measures, controlling for all covariates and global cognition.
Results
Participant-reported IADL, although associated with global cognition, was more strongly associated with GDS and NEO-FFI scores (conscientiousness and neuroticism). Informant-reported IADL was strongly associated with both global cognition and participants’ GDS scores. STAM scores were not associated with participants’ GDS or NEO-FFI scores; instead, they were predicted by demographics and global cognition.
Conclusion
These results suggest that performance-based measures of IADL may provide more objective and reliable insight into an individual’s underlying functional ability and are less impacted by the participants’ mood and personality compared to subjectively reported IADL. We argue that performance-based IADL measures are preferable when trying to accurately assess everyday functional ability and its relationship to cognitive status. Where performance-based measures are not available (e.g., in some clinical settings), informant ratings should be sought as they are less influenced by the participant’s personality and mood compared to self-reports.
... We include here several widely used clinical screening tools that may be used by the clinician to measure patient-reported outcomes in patients with cancer (Table 3) [117][118][119][120][121][122][123][124][125][126][127][128]. Patient-reported outcome measures should be selected carefully, based on their purpose, context, and the issue/symptom to be investigated. ...
Preservation of cognitive function is an important outcome in oncology. Optimal patient management requires an understanding of cognitive effects of the disease and its treatment and an efficacious approach to assessment and management of cognitive dysfunction, including selection of treatments to minimize the risk of cognitive impairment. Awareness is increasing of the potentially detrimental effects of cancer-related cognitive dysfunction on functional independence and quality of life. Prostate cancer occurs most often in older men, who are more likely to develop cognitive dysfunction than younger individuals; this population may be particularly vulnerable to treatment-related cognitive disorders. Prompt identification of treatment-induced cognitive dysfunction is a crucial aspect of effective cancer management. We review the potential etiologies of cognitive decline in patients with prostate cancer, including the potential role of androgen receptor pathway inhibitors; commonly used tools for assessing cognitive function validated in metastatic castration-resistant prostate cancer and adopted in non-metastatic castration-resistant prostate cancer trials; and strategies for management of cognitive symptoms. Many methods are currently used to assess cognitive function. The prevalence and severity of cognitive dysfunction vary according to the instruments and criteria applied. Consensus on the definition of cognitive dysfunction and on the most appropriate approaches to quantify its extent and progression in patients treated for prostate cancer is lacking. Evidence-based guidance on the appropriate tools and time to assess cognitive function in patients with prostate cancer is required.
... We used the dataset generated by [7] for our feature selection. [13], Alzheimer's Disease Assessment Scale (ADAS) [2], Functional Activities Questionnaire (FAQ) [14], Everyday Cognition -Patient scale [15], Geriatric Depression Scale [16], and Neuropsychological Battery (NB) and used multiple methods of feature selection to generate a set of 35 sub-features which were frequently selected, and assigned time costs in seconds to these subfeatures [7]. In this dataset, Clinical Dementia Rating Sum-of-Boxes (CDR-SB) rating was used as a measure of dementia severity [7]. ...
Current machine learning techniques for dementia diagnosis often do not take into account real-world practical constraints, which may include, for example, the cost of diagnostic assessment time and financial budgets. In this work, we built on previous cost-sensitive feature selection approaches by generalising to multiple cost types, while taking into consideration that stakeholders attempting to optimise the dementia care pathway might face multiple non-fungible budget constraints. Our new optimisation algorithm involved the searching of cost-weighting hyperparameters while constrained by total budgets. We then provided a proof of concept using both assessment time cost and financial budget cost. We showed that budget constraints could control the feature selection process in an intuitive and practical manner, while adjusting the hyperparameter increased the range of solutions selected by feature selection. We further showed that our budget-constrained cost optimisation framework could be implemented in a user-friendly graphical user interface sandbox tool to encourage non-technical users and stakeholders to adopt and to further explore and audit the model -a humans-in-the-loop approach. Overall, we suggest that setting budget constraints initially and then fine tuning the cost-weighting hyperparameters can be an effective way to perform feature selection where multiple cost constraints exist, which will in turn lead to more realistic optimising and redesigning of dementia diagnostic assessments.
Clinical Relevance
By optimising diagnostic accuracy against various costs (e.g. assessment administration time and financial budget), predictive yet practical dementia diagnostic assessments can be redesigned to suit clinical use.
... The questionnaire asks care partners to assess pwMCI's ability to perform instrumental everyday tasks independently in the past 4 weeks. This is a widely used measure for IADLs and has been shown to discriminate between cognitively normal controls and pwMCI [36]. ...
Comparative effectiveness of behavioral interventions to mitigate the impacts of degeneration-based cognitive decline is not well understood. To better address this gap, we summarize the studies from the Healthy Action to Benefit Independence & Thinking (HABIT®) program, developed for persons with mild cognitive impairment (pwMCI) and their partners. HABIT® includes memory compensation training, computerized cognitive training (CCT), yoga, patient and partner support groups, and wellness education. Studies cited include (i) a survey of clinical program completers to establish outcome priorities; (ii) a five-arm, multi-site cluster randomized, comparative effectiveness trial; (iii) and a three-arm ancillary study. PwMCI quality of life (QoL) was considered a high-priority outcome. Across datasets, findings suggest that quality of life was most affected in groups where wellness education was included and CCT withheld. Wellness education also had greater impact on mood than CCT. Yoga had a greater impact on memory-dependent functional status than support groups. Yoga was associated with better functional status and improved caregiver burden relative to wellness education. CCT had the greatest impact on cognition compared to yoga. Taken together, comparisons of groups of program components suggest that knowledge-based interventions like wellness education benefit patient well-being (e.g., QoL and mood). Skill-based interventions like yoga and memory compensation training aid the maintenance of functional status. Notably, better adherence produced better outcomes. Future personalized intervention approaches for pwMCI may include different combinations of behavioral strategies selected to optimize outcomes prioritized by patient values and preferences.
... Specifically, the considered CFAs were MMSE [3], Montreal Cognitive Assessment (MoCA) [25], Alzheimer's Disease Assessment Scale (ADAS) [2], Functional Activities Questionnaire (FAQ) [26], Everyday Cognition -Patient scale [27], Geriatric Depression Scale [28], and Neuropsychological Battery (NB). Within these CFAs, 113 assessment items were combined with patient demographic variables (age and education level) into one data table for feature selection. ...
Objective:
Despite the potential of machine learning techniques to improve dementia diagnostic processes, research outcomes are often not readily translated to or adopted in clinical practice. Importantly, the time taken to administer diagnostic assessment has yet to be taken into account in feature-selection based optimisation for dementia diagnosis. We address these issues by considering the impact of assessment time as a practical constraint for feature selection of cognitive and functional assessments in Alzheimer's disease diagnosis.
Methods:
We use three different feature selection algorithms to select informative subsets of dementia assessment items from a large open-source dementia dataset. We use cost-sensitive feature selection to optimise our feature selection results for assessment time as well as diagnostic accuracy. To encourage clinical adoption and further evaluation of our proposed accuracy-vs-cost optimisation algorithms, we also implement a sandbox-like toolbox with graphical user interface to evaluate user-chosen subsets of assessment items.
Results:
We find that there are subsets of accuracy-cost optimised assessment items that can perform better in terms of diagnostic accuracy and/or total assessment time than most other standard assessments.
Discussion:
Overall, our analysis and accompanying sandbox tool can facilitate clinical users and other stakeholders to apply their own domain knowledge to analyse and decide which dementia diagnostic assessment items are useful, and aid the redesigning of dementia diagnostic assessments. Clinical Impact (Clinical Research): By optimising diagnostic accuracy and assessment time, we redesign predictive and efficient dementia diagnostic assessments and develop a sandbox interface to facilitate evaluation and testing by clinicians and non-specialists.
... Clinical cut points: hypertension, BP > 140/90 in older adults < 60 years of age and 150/90 in older adults of 60 + years of age(James et al., 2014); functional dependence, FAQ ≥ 6(Teng et al., 2010); presence of depressive symptoms, GDS > 9 (Yesavage and Sheikh, 1986); cognitive impairment, MMSE < 24(Folstein et al., 1975). ...
Background: Cerebrovascular dysfunction has been proposed as a possible mechanism underlying cognitive impairment in the context of type 2 diabetes mellitus (DM). Although magnetic resonance imaging (MRI) evidence of cerebrovascular disease, such as white matter hyperintensities (WMH), is often observed in DM, the vascular dynamics underlying this pathology remain unclear. Thus, we assessed the independent and combined effects of DM status and different vascular hemodynamic measures (i.e., systolic, diastolic, and mean arterial blood pressure and pulse pressure index [PPi]) on WMH burden in cognitively unimpaired (CU) older adults and those with mild cognitive impairment (MCI).
Methods: 559 older adults (mean age: 72.4 years) from the Alzheimer’s Disease Neuroimaging Initiative were categorized into those with diabetes (DM+; CU = 43, MCI = 34) or without diabetes (DM-; CU = 279; MCI = 203). Participants underwent BP assessment, from which all vascular hemodynamic measures were derived. T2-FLAIR MRI was used to quantify WMH burden. Hierarchical linear regression, adjusting for age, sex, BMI, intracranial volume, CSF amyloid, and APOE ε4 status, examined the independent and interactive effects of DM status and each vascular hemodynamic measure on total WMH burden.
Results: The presence of DM ( p = 0.046), but not PPi values ( p = 0.299), was independently associated with greater WMH burden overall after adjusting for covariates. Analyses stratified by cognitive status revealed a significant DM status x PPi interaction within the MCI group ( p = 0.001) such that higher PPi values predicted greater WMH burden in the DM + but not DM- group. No significant interactions were observed in the CU group (all p s > 0.05).
Discussion: Results indicate that higher PPi values are positively associated with WMH burden in diabetic older adults with MCI, but not their non-diabetic or CU counterparts. Our findings suggest that arterial stiffening and reduced vascular compliance may have a role in development of cerebrovascular pathology within the context of DM in individuals at risk for future cognitive decline. Given the specificity of these findings to MCI, future exploration of the sensitivity of earlier brain markers of vascular insufficiency (i.e., prior to macrostructural white matter changes) to the effects of DM and arterial stiffness/reduced vascular compliance in CU individuals is warranted.
... The "Not applicable/Never did" responses were coded appropriately. This is a widely used measure for IADLs and has been shown to discriminate between cognitively normal controls and pwMCI [24]. ...
Background:
In Alzheimer's disease and related disorders (ADRD) research, common outcome measures include cognitive and functional impairment, as well as persons with mild cognitive impairment (pwMCI) and care partner self-reported mood and quality of life. Studies commonly analyze these measures separately, which potentially leads to issues of multiple comparisons and/or multicollinearity among measures while ignoring the latent constructs they may be measuring.
Objective:
This study sought to examine the latent factor structure of a battery of 12-13 measures of domains mentioned above, used in a multicomponent behavioral intervention (The HABIT® program) for pwMCI and their partners.
Methods:
Exploratory factor analysis (EFA) involved 214 pwMCI-partner pairs. Subsequent Confirmatory factor analyses (CFA) used 730 pairs in both pre- and post-intervention conditions.
Results:
EFA generated a three-factor model. Factors could be characterized as partner adjustment (29.9%), pwMCI adjustment (18.1%), and pwMCI impairment (12.8%). The subsequent CFA confirmed our findings, and the goodness-of-fit for this model was adequate in both the pre- (CFI = 0.937; RMSEA = 0.057, p = 0.089) and post-intervention (CFI = 0.942; RMSEA = 0.051, p = 0.430) groups.
Conclusion:
Results demonstrated a stable factor structure across cohorts and intervention conditions suggesting that three broad factors may provide a straightforward and meaningful model to assess intervention outcome, at least during the MCI phase of ADRD.
... The Mini-Mental State Examination (MMSE) is a numeric scale to test cognitive functions, including attention, calculation, and responsiveness to simple commands (Tombaugh and McIntyre, 1992). The Functional Activities Questionnaire (FAQ) evaluates instrumental activities of daily life, such as financial management and meal preparation (Teng et al., 2010). The Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) mainly measures cognitive ability such as word recall, comprehension of spoken language, and orientation (Cano et al., 2010). ...
Imaging genetics combines neuroimaging and genetics to assess the relationships between genetic variants and changes in brain structure and metabolism. Sparse canonical correlation analysis (SCCA) models are well-known tools for identifying meaningful biomarkers in imaging genetics. However, most SCCA models incorporate only diagnostic status information, which poses challenges for finding disease-specific biomarkers. In this study, we proposed a multi-task sparse canonical correlation analysis and regression (MT-SCCAR) model to reveal disease-specific associations between single nucleotide polymorphisms and quantitative traits derived from multi-modal neuroimaging data in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. MT-SCCAR uses complementary information carried by multiple-perspective cognitive scores and encourages group sparsity on genetic variants. In contrast with two other multi-modal SCCA models, MT-SCCAR embedded more accurate neuropsychological assessment information through linear regression and enhanced the correlation coefficients, leading to increased identification of high-risk brain regions. Furthermore, MT-SCCAR identified primary genetic risk factors for Alzheimer’s disease (AD), including rs429358, and found some association patterns between genetic variants and brain regions. Thus, MT-SCCAR contributes to deciphering genetic risk factors of brain structural and metabolic changes by identifying potential risk biomarkers.
Background
Mild Cognitive Impairment (MCI) usually precedes the symptomatic phase of dementia and constitutes a window of opportunities for preventive therapies.
Objectives
The objective of this study was to predict the time an MCI patient has left to reach dementia and obtain the most likely natural history in the progression of MCI towards dementia.
Methods
This study was conducted on 633 MCI patients and 145 subjects with dementia through 4726 visits over 15 years from Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A combination of data from AT(N) profiles at baseline and longitudinal predictive modeling was applied. A data-driven approach was proposed for categorical diagnosis prediction and timeline estimation of cognitive decline progression, which combined supervised and unsupervised learning techniques.
Results
A reduced vector of only neuropsychological measures was selected for training the models. At baseline, this approach had high performance in detecting subjects at high risk of converting from MCI to dementia in the coming years. Furthermore, a Disease Progression Model (DPM) was built and also verified using three metrics. As a result of the DPM focused on the studied population, it was inferred that amyloid pathology (A+) appears about 7 years before dementia, and tau pathology (T+) and neurodegeneration (N+) occur almost simultaneously, between 3 and 4 years before dementia. In addition, MCI-A+ subjects were shown to progress more rapidly to dementia compared to MCI-A- subjects.
Conclusion
Based on proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicated that only a single cerebrospinal fluid sample is necessary during the prodromal phase of AD. Prediction from MCI into dementia and its timeline can be achieved exclusively through neuropsychological measures.
Preliminary validity of a computer‐based test of everyday function (Virtual Kitchen Challenge [VKC]) was examined against brain‐imaging markers of cerebrovascular disease and in contrast to conventional neuropsychological and self‐report measures. Twenty community‐dwelling older adults ( n = 6 mild cognitive impairment) performed simulated breakfast and lunch tasks using a computer touchscreen (VKC). Automated measures (completion time, proportion time off screen, etc.) were computed during training and test conditions. White matter hyperintensity (WMH) volumes from brain magnetic resonance imaging and conventional measures of cognition and function also were obtained. VKC completion time and proportion time off screen improved significantly from training to test and were significantly associated with WMH volume ( r > 0.573). VKC measures and WMH were not significantly correlated with conventional cognitive or self‐report measures. The VKC holds promise as a valid measure of subtle functional difficulties in older adults that is sensitive to change and cerebrovascular pathology, highlighting its potential for clinical trials.
Highlights
Virtual Kitchen Challenge (VKC) scores showed significant improvement from training to test conditions.
VKC scores (completion time and proportion of time off screen) were associated with a neuroimaging biomarker of brain health (white matter hyperintensities).
Emerging therapies have shown promising results for slowing the progression of Alzheimer’s disease (AD). However, the potential impact of these therapies on real-world outcomes remains to be explored.
To examine the impact of slowing AD progression on functional abilities and behavioral symptoms.
Retrospective observational study.
Data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005–11/2021, primary analysis) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (09/2005–03/2022, sensitivity analysis) were used.
Individuals with mild cognitive impairment (MCI) or mild dementia, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score 0.5–9.0 (inclusive; first visit defined as the index date), and confirmed amyloid positivity were identified in NACC. In ADNI, individuals with at least one clinical center visit with a clinical assessment of MCI or mild dementia and confirmed amyloid positivity were identified.
Hypothetical effects of slowing disease progression as assessed by CDR-SB on functional and behavioral outcomes including the Functional Activities Questionnaire (FAQ) score, Neuropsychiatric Inventory Questionnaire (NPI-Q) score, and the probability of complete dependence over five years were evaluated using multivariable regression among NACC participants, separately for the subgroups with MCI and mild dementia at baseline, respectively. For the ADNI sensitivity analysis, the hypothetical effects of slowing disease progression were evaluated for FAQ score using multivariable regression among the MCI participants only.
Compared with natural disease progression, slowing progression by 20% over five years for NACC participants with MCI and mild dementia, respectively, would result in 1.7-point (10.8%) and 1.6-point (12.9%) less deterioration based on FAQ; 0.5-point (20.3%) and 0.5-point (19.3%) less deterioration based on NPI-Q; 4.7 percentage-point (22.2%) and 10.1 percentage-point (21.6%) lower probability of complete dependence. Among ADNI participants, delaying disease progression by 20% or 30% over 4 years would avert deterioration based on FAQ of 1.1 points (20.4%) and 1.6 points (29.6%), respectively, compared to natural disease progression.
Slowing early AD progression could result in preservation of functional and behavioral attributes and functional autonomy for longer.
Background
The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID‐19 pandemic, and lay the foundation for future work using this cohort.
Methods
SAGES II is a prospective observational cohort study of community‐dwelling adults age 65 and older undergoing major non‐cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID‐19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality.
Results
About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty‐eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID‐19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1‐month follow‐up; nearly 90% of enrolled participants completed interviews through 6‐month follow‐up.
Conclusion
While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers—including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.
Introduction:
GERAS-US prospectively characterized clinical and economic outcomes of early symptomatic Alzheimer's disease (AD). Societal cost changes were examined in amyloid-positive patients with mild cognitive impairment due to AD (MCI) and mild dementia due to AD (MILD).
Methods:
Cognition, function, and caregiver burden were assessed using Mini-Mental State Examination (MMSE), Cognitive Function Index (CFI), and Zarit Burden Interview, respectively. Costs are presented as least square mean for the overall population and for MCI versus MILD using mixed model repeated measures.
Results:
MMSE score and CFI worsened. Total societal costs (dollars/month) for MCI and MILD, respectively, were higher at baseline ($2430 and $4063) but steady from 6 ($1977 and $3032) to 36 months ($2007 and $3392). Direct non-medical costs rose significantly for MILD. Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months.
Discussion:
Function and cognition declined in MILD. Non-medical costs reflect the increasing impact of AD even in its early stages.
Highlights:
In the GERAS-US study, total societal costs for patients with mild cognitive impairment due to Alzheimer's disease (MCI) and mild dementia due to Alzheimer's disease (MILD) were higher at baseline but steady from 6 to 36 months.Mini-Mental State Examination (MMSE) and Cognitive Function Index (CFI) worsened; the rate of decline was significant for patients with MILD but not for those with MCI.There was a rise in direct non-medical costs at 36 months for patients with MILD.Caregiver burden was higher for MILD versus MCI at 12, 18, and 24 months.Slowing the rate of disease progression in this early symptomatic population may allow patients to maintain their ability to carry out everyday activities longer.
Background:
Heightened risks of cognitive impairment, disability, and barriers to care among sexual and gender minority (SGM) older adults are well documented. To date, culturally responsive evidence-based dementia interventions for this population do not exist.
Objective:
This study describes the design of the first randomized controlled trial (RCT) testing a culturally responsive cognitive behavioral and empowerment intervention, Innovations in Dementia Empowerment and Action (IDEA), developed to address the unique needs of SGM older adults living with dementia and care partners.
Methods:
IDEA is a culturally enhanced version of Reducing Disability in Alzheimer's Disease (RDAD), an efficacious, non-pharmaceutical intervention for people with dementia and care partners. We utilized a staggered multiple baseline design with the goal to enroll 150 dyads randomized into two arms of 75 dyads each, enhanced IDEA and standard RDAD.
Results:
IDEA was adapted using findings from the longitudinal National Health, Aging, and Sexuality/Gender study, which identified modifiable factors for SGM older adults, including SGM-specific discrimination and stigma, health behaviors, and support networks. The adapted intervention employed the original RDAD strategies and enhanced them with culturally responsive empowerment practices designed to cultivate engagement, efficacy, and support mobilization. Outcomes include adherence to physical activity, reduction in perceived stress and stigma, and increased physical functioning, efficacy, social support, engagement, and resource use.
Conclusion:
IDEA addresses contemporary issues for underserved populations living with dementia and their care partners. Our findings will have important implications for marginalized communities by integrating and evaluating the importance of cultural responsiveness in dementia and caregiving interventions.
Objective:
Assessing one's functional capacity-in addition to neuropsychological performance-is essential for determining neurocognitive status, and functional assessment is often provided via informant report. Although informant characteristics have been shown to influence reports of participant functioning, the degree to which they moderate relationships between reported functioning and participant performance on neuropsychological testing is unclear. Moreover, associations among informant characteristics, reported functioning, and neuropsychological performance have not been adequately examined with non-Hispanic Black (NHB) samples, despite this population's disproportionately high risk of Alzheimer's disease and related dementias.
Method:
In this cross-sectional observational study, we examined the influence of informant characteristics on informant reports of participant functioning (assessed via the Functional Activities Questionnaire [FAQ]) and associations between reported functioning and participant performance on neuropsychological testing, among NHB adult participants in the National Alzheimer's Coordinating Center cohort (n = 1024).
Results:
Informants who were younger, female, more educated, knew participants longer, or lived with participants reported poorer participant functioning (p < .001). However, younger (vs. older) informants provided reports of functioning that were more predictive of visuoconstructional ability and visual memory, and male (vs. female) informants provided reports of functioning that were more predictive of verbal memory, visuoconstructional ability and visual memory, and language (ps < .001).
Conclusions:
Within the context of neurocognitive evaluations of NHB participants, informant characteristics may influence subjective reports of participants' functioning and the extent to which reported functioning corroborates objective participant performance on neuropsychological testing.
Introduction:
We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome.
Methods:
A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria.
Results:
Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes.
Discussion:
This work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.
Background and Objectives
The University of California, San Francisco Memory and Aging Center (UCSF-MAC) led the development and tested a collaborative care model delivered by lay care team navigators (CTNs) with support from a multidisciplinary team known as the Care Ecosystem (CE). We report the results from the application of the CE within a non-academic healthcare system.
Research Design and Methods
The CE team at HealthPartners consisted of two CTNs, a social worker, an RN, a program coordinator, and a behavioral neurologist. Intake forms were developed to collect demographic, baseline, and annual longitudinal data at one year related to dementia severity and care partner status. Experience surveys were completed every 6 months by participating care partners. All data was entered into REDCap.
Results
A total of 570 PWD-caregiver dyads were recruited into the CE: 53% PWDs female, average age 75.2 ± 9.43, 19% living within rural communities. Of the 173 dyads assessed at one year, 58% of care partners responded to surveys, and 67% of those provided data about their CE experience through survey data. At one year, PWDs progressed in disease severity and functional impairment, although care partner burden and mood remained unchanged. We observed a significant reduction in care partner reported emotional challenges associated with caregiving, sleep problems, and obtaining care partner help at one year. Eighty-six percent of care partners reported feeling supported by their CTN nearly always or quite frequently, and 88% rated the CTN as highly responsive to what was important to them.
Discussion and Implications
The CE was feasible and well-received within a non-academic healthcare system.
Background:
Lesbian and gay older adults have health disparities that are risk factors for Alzheimer's disease, yet little is known about the neurocognitive aging of sexual minority groups.
Objective:
To explore cross-sectional and longitudinal dementia outcomes for adults in same-sex relationships (SSR) and those in mixed-sex relationships (MSR).
Methods:
This prospective observational study utilized data from the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) collected from contributing Alzheimer's Disease Research Centers. Participants were adults aged 55+ years at baseline with at least two visits in NACC UDS (from September 2005 to March 2021) who had a spouse, partner, or companion as a co-participant. Outcome measures included CDR ® Dementia Staging Instrument, NACC UDS neuropsychological testing, and the Functional Activities Questionnaire. Multivariable linear mixed-effects models accounted for center clustering and repeated measures by individual.
Results:
Both MSR and SSR groups experienced cognitive decline regardless of baseline diagnosis. In general, MSR and SSR groups did not differ statistically on cross-sectional or longitudinal estimates of functioning, dementia severity, or neuropsychological testing, with two primary exceptions. People in SSR with mild cognitive impairment showed less functional impairment at baseline (FAQ M = 2.61, SD = 3.18 vs. M = 3.97, SD = 4.53, respectively; p < 0.01). The SSR group with dementia had less steep decline in attention/working memory (β estimates = -0.10 versus -0.18; p < 0.01).
Conclusion:
Participants in SSR did not show cognitive health disparities consistent with a minority stress model. Additional research into protective factors is warranted.
Background:
Cerebral microvascular dysfunction is commonly seen in Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Cerebrovascular reactivity (CVR) to CO2 reflects cerebral microvascular health and may be modulated by the renin-angiotensin system (RAS). This study aimed to investigate the effects of RAS modulation on CVR in individuals with mild cognitive impairment (MCI) due to underlying vascular or AD etiologies.
Methods:
This study presents findings of candesartan's effects on the secondary outcomes of two double-blind randomized clinical trials of 12-month therapy of candesartan vs. lisinopril in VCI (CALIBREX) and candesartan vs. placebo in prodromal AD (CEDAR). Primary outcome results of these trials have been reported in previous publications. Participants underwent identical brain BOLD-CVR in response to a 2-minute CO2 challenge at baseline and 12 months. Regions of interest and voxel-wise CVR maps were derived from BOLD signal changes during CO2 challenge. CVR effects were compared between candesartan and lisinopril (CALIBREX) and candesartan and placebo (CEDAR) using mixed model repeated measures.
Results:
Data from 102 participants in the CALIBREX study (mean age 65 yrs, 45% female, 63% African American) and 59 in the CEDAR study (mean age 67 yrs, 32% female, 20% African American) were analyzed. Candesartan was associated with improved whole brain CVR compared to placebo in the CEDAR study (adjusted within-group mean difference for candesartan: 0.27 (95% CI: 0.006, 0.53) vs. placebo: -0.17 (95% CI: 0.42, 0.08), p-value=0.018), and compared to lisinopril in the CALIBREX study (adjusted within group mean difference for candesartan 0.28 (95% CI: 0.10, 0.46) vs. lisinopril -0.08 (95% CI: -0.31, 0.14), p-value=0.012), independent of blood pressure. In an exploratory meta-analysis of the two trials, improved CVR in the hippocampus was linked to improved attention and working memory (p=0.044) and a trend for improved executive function (p=0.087) with candesartan therapy.
Conclusions:
This study suggests that candesartan is associated with improved microvascular function in mild cognitive impairment, and these findings are independent of its blood pressure effect in these VCI and prodromal AD populations.
Better treatments are needed to improve cognition and brain health in people with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Transcutaneous vagus nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms including, but not limited to, projection to the locus coeruleus, the brain’s primary source of norepinephrine, and reduction in inflammation. Neuropathological data suggest that the locus coeruleus may be an early site of tau pathology in AD. Thus, tVNS may modify the activity of networks that are impaired and progressively deteriorate in patients with MCI and AD. Fifty patients with MCI (28 women) confirmed via diagnostic consensus conference prior to MRI (sources of info: Montreal Cognitive Assessment Test (MOCA), Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test — Revised (HVLT-R) and medical record review) underwent resting state functional magnetic resonance imaging (fMRI) on a Siemens 3 T scanner during tVNS (left tragus, n = 25) or sham control conditions (left ear lobe, n = 25). During unilateral left tVNS, compared with ear lobe stimulation, patients with MCI showed alterations in functional connectivity between regions of the brain that are important in semantic and salience functions including regions of the temporal and parietal lobes. Furthermore, connectivity from hippocampi to several cortical and subcortical clusters of ROIs also demonstrated change with tVNS compared with ear lobe stimulation. In conclusion, tVNS modified the activity of brain networks in which disruption correlates with deterioration in AD. These findings suggest afferent target engagement of tVNS, which carries implications for the development of noninvasive therapeutic intervention in the MCI population.
Background:
The high burden of dementia and Alzheimer's disease (AD) increases substantially as disease progresses. Characterizing early patterns of health care utilization among patients who develop cognitive impairment may deepen our understanding of early disease trajectory and potentially facilitate timely diagnosis and management.
Objective:
Describe clinical characteristics, healthcare utilization, and costs in early-stage dementia by disease severity and amyloid-β status before enrollment in an observational study (GERAS-US).
Methods:
Consented patients' GERAS-US data were linked to available five-years of Medicare claims history before GERAS-US enrollment. Clinical characteristics, comorbidity, and pre-/post-diagnosis healthcare use and costs were assessed. Continuous and categorical variables were compared between severity and amyloid-status cohorts using t-test and Chi-square statistics; linear regression models were used to compare cost and utilization measures after adjusting for differences in patients' observation time. Relative likelihood of observed diagnoses, comorbidity, and prescription drug use among cohorts were presented as OR and 90% confidence interval (CI).
Results:
Of 174 patients clinically diagnosed with early dementia (mild cognitive impairment (MCI): 101; mild dementia (MILD): 73), 55% were amyloid-positive. Memory loss was more likely in MILD versus MCI (OR:1.85, 90% CI 1.10-3.09) and in amyloid-positive versus amyloid-negative cohorts (OR:1.98, 90% CI 1.19-3.29). Mean annual healthcare costs after cognitive impairment/dementia diagnosis were significantly higher for MILD versus MCI ($1191 versus $712, p = 0.067) and amyloid-negative versus amyloid-positive ($1281 versus $701, p = 0.034). Diabetes was more prevalent in MILD and amyloid-negative cohorts.
Conclusion:
Comorbidity and economic burden increased in earliest stages of MCI and MILD and were higher in patients who were amyloid-negative.
Background: Gabapentin is increasingly prescribed to older adults, which raises concerns about its potential to cause neurocognitive changes. Therefore, we aimed to examine the association of gabapentin use with neurocognitive changes (i.e., cognitive decline, functional status decline, and motor function change) in older adults.
Methods: We conducted a retrospective cohort study using the National Alzheimer’s Coordinating Center Uniform Data Set (UDS; September 2005-March 2021 data freeze). From the eligible sample (≥age 65 years), we identified cognitively normal new-users of gabapentin and the visit they initiated gabapentin (i.e., index visit). Initiators were matched to randomly selected nonusers on year of UDS enrollment and visit number from enrollment to index. Cognitive decline was defined as any increase in the Clinical Dementia Rating global score (CDRGLOB) and as a 1-point increase in CDR sum of boxes (CDR-SB). Functional status decline was defined as a 3-point increase in the sum of the Functional Activities Questionnaire (FAQ) and as 0.3-point increase in mean FAQ. Decline in motor function was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, we used joint stabilized inverse probability of treatment weights and stabilized inverse probability of censoring weights. All analyses were conducted comparing index to index+1 and index+2 visits.
Results: From the eligible UDS participants (N = 23,059), we included 480 initiators (mean age [SD]: 78.7 [6.9]; male 34.4%); 4,320 nonusers (78.3 [7.0]; 34.4%). Gabapentin initiation was significantly associated with cognitive/functional status decline: worsening CDRGLOB at index+1 visit (odds ratio [95% confidence interval]: 1.55 [1.07, 2.25]); CDR-SB at index+1 visit (1.94 [1.22, 3.09]); and mean of FAQ at index+2 visit (1.78 [1.12, 2.83]). After excluding initiators with extant motor dysfunction (n = 21), we identified 459 initiators (78.7 [6.9]; 34.0%) and 4,131 nonusers (78.2 [6.9]; 34.7%); in this sample, gabapentin initiation was associated with increased falls at the index+2 visit (2.51 [1.19, 5.31]).
Conclusion: Gabapentin initiation was significantly associated with deleterious neurocognitive changes among older adults with initially normal cognition. Further studies are needed to examine the risk/benefit of prescribing gabapentin in older adults.
The purpose of this study was to describe a process to determine the presence of dementia and test the psychometric properties of the proposed measurement model for dementia. The model included the AD8, the Functional Activities Questionnaire, the Clinical Dementia Rating Scale, and the Saint Louis University Mental Status Examination. A total of 346 patients consented and 176 of those were determined to be eligible as a result of screening with this measurement model. The mean age of the participants was 80.70 ( SD = 9.60) and the majority were female (64%), white (66%), not Latinx (99%), and not married (67%). There was evidence of reliability based on the internal consistency of the items on all measures and the limited error associated with each item. There was evidence of construct validity based on model fit. All four measures are recommended as a pragmatic way in which to comprehensively determine evidence of dementia for research studies.
Introduction:
Autonomic dysfunction is an important feature of Lewy Body Dementia (DLB), but measurement of autonomic symptoms has been limited in both previous research and clinical practice. Accurate measurement of autonomic dysfunction has the potential to improve our understanding of the course and progression of DLB, given that autonomic symptoms typically precede cognitive impairment and are associated with functional impairment. The primary aim of this study was to examine the psychometric properties of the two versions (3.0 and 3.1) of the NACC LBD-module Autonomic Symptom Checklist (ASC).
Methods:
Psychometric analyses of the ASC (internal consistency, reliability, factor structure, and validity) were conducted on data acquired from 245 individuals with DLB from the NACC database. ASC V3.0 was contrasted on these attributes to V3.1.
Results:
Results suggested an underlying factor structure for the ASC, and confirmatory factor analysis (CFA) revealed 3 factors, which generally aligned with discrete autonomic systems. The ASC V3.0 and CFA-identified scales were comparable in terms of reliability, which were both improved relative to the ASC V3.1. In terms of ecological validity, CFA-identified items related to gastrointestinal/thermoregulation symptoms were significantly more associated with functional outcomes compared to the unitary ASC.
Conclusion:
Findings underscore the importance of differentiation within the autonomic system. Future research into autonomic symptom classes and lab-based pathophysiological measurement of autonomic dysfunction in DLB has the potential to support early identification and inform treatment planning.
Background:
The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers. The goal of this paper is to describe the study design and methods for the SAGES II study.
Methods:
The SAGES II study is a 5-year prospective observational study of 400-420 community dwelling persons, aged 65 years and older, assessed prior to scheduled surgery and followed daily throughout hospitalization to observe for development of delirium and other clinical outcomes. Delirium is measured with the Confusion Assessment Method (CAM), long form, after cognitive testing. Cognitive function is measured with a detailed neuropsychologic test battery, summarized as a weighted composite, the General Cognitive Performance (GCP) score. Other key measures include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS)/electroencephalography (EEG), and Amyloid positron emission tomography (PET) imaging. We describe the eligibility criteria, enrollment flow, timing of assessments, and variables collected at baseline and during repeated assessments at 1, 2, 6, 12, and 18 months.
Results:
This study describes the hospital and surgery-related variables, delirium, long-term cognitive decline, clinical outcomes, and novel biomarkers. In inter-rater reliability assessments, the CAM ratings (weighted kappa = 0.91, 95% confidence interval, CI = 0.74-1.0) in 50 paired assessments and GCP ratings (weighted kappa = 0.99, 95% CI 0.94-1.0) in 25 paired assessments. We describe procedures for data quality assurance and Covid-19 adaptations.
Conclusions:
This complex study presents an innovative effort to advance our understanding of the inter-relationship between delirium and dementia via novel biomarkers, collected in the context of major surgery in older adults. Strengths include the integration of MRI, TMS/EEG, PET modalities, and high-quality longitudinal data.
White matter hyperintensities (WMH), a marker of small vessel cerebrovascular disease, increase risk of developing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Less is known about the extent and pattern of WMH in pre-MCI stages, such as among those with objectively-defined subtle cognitive decline (Obj-SCD). Five hundred and fifty-nine Alzheimer's Disease Neuroimaging Initiative participants (170 cognitively unimpaired [CU]; 83 Obj-SCD; 306 MCI) free of clinical dementia or stroke completed neuropsychological testing and MRI exams. ANCOVA models compared cognitive groups on regional WMH adjusting for age, sex, and apolipoprotein E (APOE) ɛ4 frequency. Compared with the CU group, those with Obj-SCD had greater temporal, occipital, and frontal WMH whereas those with MCI had higher WMH volume across all regions (p's < 0.01). No differences in WMH volume were observed between the Obj-SCD and MCI groups (p's > 0.05). Findings add to growing evidence of associations between Obj-SCD and imaging biomarkers, providing support for utility of these criteria to capture subtle cognitive changes that are biologically based.
Early screening for Alzheimer’s disease (AD) is crucial for disease management, intervention, and healthcare resource accessibility. Medical assessments of AD diagnosis include the utilisation of biological markers (biomarkers), positron emission tomography (PET) scans, magnetic resonance imaging (MRI) images, and cerebrospinal fluid (CSF). These methods are resource intensive as well as physically invasive, whereas neuropsychological tests are fast, cost effective, and simple to administer for providing early AD diagnosis. However, neuropsychological assessments contain elements related to executive functions, memory, orientation, learning, judgment, and perceptual motor function (among others) that overlap, making it difficult to identify the key elements that trigger the progression of dementia or mild cognitive impairment (MCI). This research investigates the elements of the Functional Activities Questionnaire (FAQ) an early screening method using a data driven approach based on feature selection and classification. The aim is to determine the key items in the FAQ that may trigger AD advancement. To achieve the aim, real data observations of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project have been processed using the proposed data driven approach. The results derived by the machine learning techniques in the proposed approach on data subsets of the FAQ items with demographics show models with accuracy, sensitivity, and specificity all exceeding 90%. In addition, FAQ elements including Administration and Shopping related activities showed correlations with the progression class; these elements cover four out of the six Diagnostic and Statistical Manual’s (DSM-5’s) neurocognitive domains.
Objective
This study used multiple assessment methods to examine instrumental activities of daily living (IADLs) performance in individuals with Parkinson’s disease with mild cognitive impairment (PD-MCI) compared to individuals with mild cognitive impairment (MCI) and cognitively healthy older adults (HOA). Associations between functional performance and cognition were also examined.
Methods
Eighteen individuals with PD-MCI, 48 individuals with MCI, and 66 HOAs were assessed with multiple IADL measures, including direct observation, a performance-based measure, and self- and informant-report questionnaires. Performance on the direct-observation measure was further characterized by coding for four error types: omissions, substitutions, and inefficient and irrelevant/off-task actions.
Results
Both the PD-MCI and MCI groups performed more poorly on the overall score for all IADL measures relative to HOAs. Although the PD-MCI and MCI groups did not differ in overall performance, on the direct-observation measure, the PD-MCI group took longer and made more inefficient and irrelevant/off-task errors relative to the HOA and MCI groups, whereas the MCI group made more omission and substitution errors relative to HOAs. Further, the pattern of cognitive correlates that associated most strongly with the functional measures varied across groups and functional assessment methods.
Conclusion
Compared to HOAs, PD-MCI and MCI groups demonstrated increased difficulties performing everyday activities, and cognitive and motor abilities differentially contributed to the everyday task difficulties of these two groups.
Objectives
In Alzheimer’s Disease (AD) research, choosing appropriate method for measuring change in cognitive function over time can be challenging. The aim for this study was to examine the sensitivity of four neuropsychological tests used to measure cognition during the transition from mild cognitive impairment (MCI) to AD, and the impacts of associated covariates.
Methods
We enrolled 223 patients with MCI who progressed to AD and had completed multiple follow-up assessments in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We constructed nonlinear mixed model for multivariate longitudinal data assuming that multiple neuropsychological tests would exhibit nonlinear transformation of a common factor in the latent cognitive process underlying the progression from MCI to AD.
Results
The Clinical Dementia Rating-Sum of the Boxes (CDR-SB) and Alzheimer’s Disease Assessment Scale (11 items; ADAS-11) were more sensitive to cognitive changes in individuals with higher cognitive function, the Functional Activities Questionnaire (FAQ) was more sensitive to cognitive changes in individuals with middle cognitive function, and the Mini-Mental State Examination (MMSE) was more sensitive to cognitive changes in individuals with lower cognitive function. Gender (p = 0.0139) and educational level (p = 0.0094) had varying effects on different tests, such that men performed better on the FAQ and CDR-SB, and individuals with higher educational level tended to perform better on the FAQ and MMSE.
Conclusions
When choosing appropriate neuropsychological tests in cognitive measurements, the cognitive functional level of the patient as well as the impacts of covariates should be considered.
Background: The real prevalence of dementia in a given population must be determined through prevalence studies, using validated screening tests. Aim: To validate and determine cutoff points for a cognitive impairment screening test composed by the Folstein Mini Mental State Examination (MMSE) and Pfeffer Functional Activities Questionnaire (PFAQ). Material and methods: Validation of the diagnostic test in a sample of 100 subjects over 65 years old (85 from the project «Age associated dementias» and 15 with a confirmed diagnosis of dementia). All were subjected to a complete neuropsychological test by a trained neurologist, that constituted the «gold standard» for the diagnosis of dementia. An independent interviewer applied the MMSE to the subjects and the PFAQ to a next of kin informer. Cutoff points were calculated using ROC curves. The points with the better equilibrium between sensitivity and specificity were selected, considering differences in results between groups with low and high educational level. Results: The cutoff point for MMSE was 21/22, with a sensitivity of 93.6% (95% CI 70.6-99.7%) and a specificity of 46.1% (95% CI 34.7-57.8%). The figure for PFAQ was 5/6, with a sensitivity of 89.2% (95% CI 70.6-99.7%) and a specificity of 70.7% (95% CI 58.9-80.3%). The combination of both instruments gave a sensitivity of 94.4% (95% CI 58.9-80.3%) and a specificity of 83.3% (95% CI 72.3-90.7%). Conclusions: This screening test, using MMSE and PFAQ, has a good sensitivity and specificity for the diagnosis of dementia in Chile. Being simple and of low cost, it can be applied in primary health care (Rev Méd Chile 2004; 132: 467-78)
BACKGROUND
The real prevalence of dementia in a given population must be determined through prevalence studies, using validated screening tests.
AIM
To validate and determine cutoff points for a cognitive impairment screening test composed by the Folstein Mini Mental State Examination (MMSE) and Pfeffer Functional Activities Questionnaire (PFAQ).
MATERIAL AND METHODS
Validation of the diagnostic test in a sample of 100 subjects over 65 years old (85 from the project "Age associated dementias" and 15 with a confirmed diagnosis of dementia). All were subjected to a complete neuropsychological test by a trained neurologist, that constituted the "gold standard" for the diagnosis of dementia. An independent interviewer applied the MMSE to the subjects and the PFAQ to a next of kin informer. Cutoff points were calculated using ROC curves. The points with the better equilibrium between sensitivity and specificity were selected, considering differences in results between groups with low and high educational level.
RESULTS
The cutoff point for MMSE was 21/22, with a sensitivity of 93.6% (95% CI 70.6-99.7%) and a specificity of 46.1% (95% CI 34.7-57.8%). The figure for PFAQ was 5/6, with a sensitivity of 89.2% (95% CI 70.6-99.7%) and a specificity of 70.7% (95% CI 58.9-80.3%). The combination of both instruments gave a sensitivity of 94.4% (95% CI 58.9-80.3%) and a specificity of 83.3% (95% CI 72.3-90.7%).
CONCLUSIONS
This screening test, using MMSE and PFAQ, has a good sensitivity and specificity for the diagnosis of dementia in Chile. Being simple and of low cost, it can be applied in primary health care.
Previous studies have reported an association between executive dysfunction and the ability to perform activities of daily living (ADL)s among older adults. This study aims to examine the association between executive functions and functional status in a cross-section of older adults with varying degrees of cognitive impairment.
89 individuals (mean age 73.8 years) were recruited at a memory clinic in São Paulo, Brazil. Subjects underwent evaluation, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n = 32), mild cognitive impairment (MCI, n = 31) and mild Alzheimer's disease (AD, n = 26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Direct Assessment of Functional Status test (DAFS-R).
Significantly different total DAFS-R scores were observed across the three diagnostic groups. Patients with AD performed significantly worse in EXIT25 compared with subjects without dementia, and no significant differences were detected between NC and MCI patients. We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r =-0.872, p < 0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores.
Executive dysfunction and decline in general measures of cognitive functioning are associated with a lower ability to undertake instrumental ADLs. MCI patients showed worse functional status than NC subjects. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs.
to evaluate the use of different functional scales in detecting dementia in a population study.
the study is part of the Helsinki Ageing Study. A random sample of 795 subjects aged 75 (n = 274), 80 (n = 266) and 85 years (n = 255) was taken. The prevalences of dementia (DSM-III-R criteria) in these age groups were 4.6, 13.1 and 26.7% respectively. The functional scale scores were known for 71% of the non-demented and 66% of the demented subjects. A structured questionnaire completed by a close informant included four functional scales: the index of activities of daily living (ADL), the modified Blessed dementia scale (DS), the instrumental activities of daily living scale (IADL) and the Functional Assessment Questionnaire (FAQ).
all the functional scales discriminated demented from non-demented subjects. Based on receiver operating characteristics analysis, the area under the curve (95% confidence interval) was 0.90 (0.80-0.94) for the ADL, 0.94 (0.87-0.97) for the DS, 0.95 (0.90-0.98) for the IADL and 0.96 (0.92-0.98) for the FAQ. The effects of age, sex and education in detecting dementia were minor or non-existent in the ADL, DS and FAQ scales, but age had an effect on the performance of the IADL scale. All the scales detected even mild dementia adequately.
functional scales can be used in detecting dementia when functional assessment is already used for other purposes, such as among elderly primary care patients.
A group of 314 Spanish-speaking elders were classified in 55 participants with mild to moderate dementia, 74 participants with mild cognitive impairment (MCI), and 185 control participants, according to clinical evaluation derived. Sensitivity, specificity, and detection characteristics of frequently cognitive and functional tests were calculated in comparison with the clinical evaluation: Minimental State Examination, Brief Neuropsychological Test Battery, Short Blessed test, Pfeffer Functional Activities Questionnaire, and Blessed Dementia Scale. Influence of education on sensitivity and specificity values varied along the tests. For all the cognitive and functional measures, a great number of MCI participants who fulfilled Mayo's (Mayo's Clinical School) clinical criteria (Petersen et al., 1999) were misclassified as controls and a few were misclassified as demented. Level of education plays a very important role in both cognitive and functional assessment. The cognitive tests that are commonly used to screen demented patients may fail to detect MCI particularly in high-functioning individuals as well as those who are well educated.
To develop and validate an Instrumental Activities of Daily Living Scale for elderly people (IADL-E) to use in conjunction with cognitive screening tests for dementia in an educationally and socioculturally heterogeneous population.
Eleven IADL items were selected and weighted for major factors causing heterogeneity in the population--gender, education, social (rural/urban) setting and age. Each item was rated for its applicability (yes/no), degree of disability (scored from 0 to 2) and causative impairment (cognitive and/or physical). From this a composite index of cognitive (CDI) or physical (PDI) disability was derived. Validation was performed retrospectively on 240 subjects: 135 without and 105 with dementia by DSM-IV.
The IADL-E had a high internal consistency (alpha = 0.95). The area under the receiver operating characteristic (ROC) curve was 0.97 (CI = 0.94-0.99). A cutoff score of 16 on CDI provided a sensitivity of 0.91, specificity 0.99 and positive predictive value 0.76 (at 5% base rate). IADL-E correlated highly with clinical (DSM-IV, kappa = 0.89), functional (CDR, 0.82) and cognitive (Mini-mental Status Examination, MMSE, 0.74) diagnoses. It showed good responsiveness, with the change on CDI over a median of 23 months correlating significantly with that on MMSE (coefficient = -0.382, CI = -0.667 to -0.098; p=0.009). Individual items had good interrater and test-retest reliability.
The IADL-E is a reliable, sensitive and responsive scale of functional abilities useful in dementia screening in a socioculturally heterogeneous population.
Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.
Increasing evidence suggests that performance of the instrumental activities of daily living (IADL) can be impaired at the mild cognitive impairment (MCI) stage. Our study aimed at investigating the profiles of functional impairment in Chinese subjects with MCI.
Subjects with MCI were categorized into single-domain amnestic MCI (a-MCI) (n = 54) and multiple-domain amnestic MCI (md-MCI) (n = 93) groups. Their functional scores of Disability Assessment of Dementia (DAD) were compared with those of cognitively normal elderly controls (NC) (n = 78) and those with mild Alzheimer's disease (AD) (n = 85).
Subjects with md-MCI had intermediate performance in IADL between the NC and those with mild AD. Subjects with a-MCI had functional scores similar to those of normal controls. Age, education, and global cognitive test scores were not associated with functional scores in MCI subjects.
Our results demonstrated that Chinese older persons with md-MCI had impairment in IADL, as compared to NC and subjects with a-MCI. This finding suggests that assessment of IADL should be incorporated in the clinical evaluation of MCI.
The purpose of this study is to examine baseline differences and annualized cognitive and functional change scores in mild Alzheimer's disease (AD) patients with and without impaired activities of daily living (ADL).
We recruited 267 mild probable AD patients with at least 1 year of follow-up (NINCDS-ADRDA criteria, MMSE>or=20). Based on initial ADL scores, they were divided into 2 groups: unimpaired (n=40) and impaired (n=227). We compared the differences in annualized change scores on MMSE, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), ADL and Clinical Dementia Rating sum of box score (CDR-SB) for patients with and without functional impairment at baseline.
The group with unimpaired ADL at baseline had a significantly shorter symptom duration (p=0.01) and better neuropsychological test scores at baseline (p<0.001) than those with impaired ADL. The annualized cognitive and functional change of each group from baseline to 1-year follow-up was not significantly different on the MMSE, ADAS-cog, CDR-SB, Physical Self-Maintenance Scale and Instrumental Activities of Daily Living. After 1 year, 56% of the initially unimpaired group and 6% of the initially impaired group reported no ADL impairment.
Our study suggests that functional decline should not be required for the diagnosis of mild AD.
Impairment in instrumental activities of daily living (IADL) leads to early loss in productivity and adds significant burden to caregivers. Executive dysfunction is thought to be an important contributor to functional impairment. The objective of this study was to investigate the relationship between executive function and IADL in a large cohort of well-characterized normal older controls, mild cognitive impairment (MCI), and patients with mild Alzheimer's disease, separately as well as across the entire sample, while accounting for demographic, cognitive, and behavioral factors.
Subjects with baseline clinical datasets (n=793) from the Alzheimer's Disease Neuroimaging Initiative study (228 normal older controls, 387 MCI, 178 Alzheimer's disease) were included in the analysis. A multiple regression model was used to assess the relationship between executive function and IADL.
A multiple regression model, including diagnosis, global cognitive impairment, memory performance, and other covariates demonstrated a significant relationship between executive dysfunction and IADL impairment across all subjects (R2=.60, P<.0001 for model; Digit Symbol, partial ß=-.044, P=.005; Trailmaking Test B-A, quadratic relation, P=.01). Similarly, an analysis using MCI subjects only yielded a significant relationship (R2=.16, P<.0001 for model; Digit Symbol, partial ß=-.08, P=.001).
These results suggest that executive dysfunction is a key contributor to impairment in IADL. This relationship was evident even after accounting for degree of memory deficit across the continuum of cognitive impairment and dementia.
The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
Greater cognitive and functional deficits in mild cognitive impairment (MCI) are associated with higher rates of dementia. We explored the relationship between these factors by comparing instrumental activities of daily living (IADLs) among cognitive subtypes of MCI and examining associations between IADL and neuropsychological indices.
We analyzed data from 1,108 MCI and 3,036 normal control subjects included in the National Alzheimer's Coordinating Center Uniform Data Set who were assessed with the Functional Activities Questionnaire (FAQ).
IADL deficits were greater in amnestic than nonamnestic MCI, but within these subgroups, did not differ between those with single or multiple domains of cognitive impairment. FAQ indices correlated significantly with memory and processing speed/executive function.
IADL deficits are present in both amnestic MCI and nonamnestic MCI but are not related to the number of impaired cognitive domains. These cross-sectional findings support previous longitudinal reports suggesting that cognitive and functional impairments in MCI may be independently associated with dementia risk.
The purposes of this study were to describe restrictions in instrumental activities of daily living (IADL) in mild cognitive impairment (MCI) and to assess different patterns of IADL in each MCI subtype.
A total of 566 participants, those not cognitively impaired (NCI; n = 311) and MCI patients (n = 255), 60-94 years old (71.25 +/- 6.00), were examined. Neuropsychological tests were administered to participants, and each MCI patient was classified into one of four subtypes. They completed the Barthel ADL and Seoul-IADL (S-IADL) for ADL measures.
There was a significant difference between NCI and MCI in terms of total S-IADL scores. ANOVA and a post hoc Dunnett analysis revealed that MCI patients performed significantly worse on four out of a total 15 items (i.e. telephone, transportation, finances and household appliances). ANCOVA showed a significant difference in S-IADL-MCI (4 of 15 items) between NCI and amnestic MCI-multiple domains after adjusting for age, gender, education and Geriatric Depression Scale (F = 4.257, d.f. = 1,556, p = 0.002).
These findings suggest that scorings of specific IADL items are different in MCI subjects, and these items can possibly help in the identification of MCI subtypes, especially amnestic MCI-multiple domains.
Vascular dementia is a common and potentially reversible type of dementing illness. Simple, yet valid, assessment instruments are needed to quantitate the severity of cognitive and functional impairment in vascular dementia patients seen in consultation or studied in therapeutic trails. Among sixty-three patients with known ischemic cerebrovascular disease, we found thirteen who satisfied research criteria for vascular dementia, nineteen who were "borderline" and thirty-one who were not demented. We administered the Cognitive Capacity Screening Examination and the Functional Activities Questionnaire to these patients and found both tests capable of distinguishing demented from nondemented groups with a high degree of sensitivity and specificity. This battery of assessment instruments was especially helpful in evaluating patients who fell into the "borderline" category. Both tests can be easily administered at the bedside or during routine office visits.
Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.
Two measures of social function designed for community studies of normal aging and mild senile dementia were evaluated in
195 older adults who underwent neurological, cognitive, and affective assessment. An examining and a reviewing neurologist
and a neurologically trained nurse independently rated each on a scale of functional capacity. Interrater reliability was
high (examining Vs. reviewing neurologist, r = .97; examining neurologist Vs. Nurse, tau b = .802; p < .001 for both comparisons). Estimates Correlated well with an established measure of social function and with results of
cognitive tests. Alternate Informants Evaluated participants on the functional activities questionnaire and the Instrumental
Activities of Daily Living Scale. The Functional Activities Questionnaire was superior to the Instrumental Activities of Daily
Living Scale in discriminating among functional levels and in predicting neurologist ratings and cognitive scores. Used alone
as a diagnostic tool, the Functional Activities Questionnaire was more sensitive than the Instrumental Activities of Daily
Living Scale (.85 vs. .57) and almost as specific (.81 Vs. .92) in distinguishing between normal and demented individuals.
The authors investigated differences in functional ability among three groups of subjects who were not diagnosed with dementia: normal control (NC) subjects (n=35); Clinical Dementia Rating Scale (CDRS) score of 0 (minimal impairment; n=26); and CDRS 0. 5 (questionable dementia; n=42). CDRS 0 and 0. 5 patients reported significantly poorer functioning than NCs in household and other activities, but CDRS 0 and CDRS 0. 5 groups did not differ in self-reported functioning. It is likely that CDRS 0. 5 patients overestimated their functional abilities. Correlations between self- and informant reports of functional status were significantly lower in the CDRS 0. 5 group than in the CDRS 0 group, an important finding for clinical management because patients with questionable dementia may actually be more impaired than they admit. Informants' reports or standardized performance-based assessment should be considered in the clinical evaluation of such patients.
To investigate prevalence of "cognitive impairment, no dementia" (CIND) in the Italian older population, evaluating the association with cardiovascular disease and the impact on activities of daily living (ADL). CIND may provide pathogenic clues to dementia and independently affect ADL.
Cross-sectional examination in the context of the Italian Longitudinal Study on Aging.
Random population sample from eight Italian municipalities.
A total of 3,425 individuals aged 65-84 years, residing in the community or institutionalized.
Study participants were screened for cognitive impairment by using the Mini-Mental State Examination. Trained neurologists examined those scoring <24. CIND diagnosis relied on clinical and neuropsychological examination, informant interview, and assessment of functional activities. Age-related cognitive decline (ARCD) was diagnosed in CIND cases without neuropsychiatric disorders responsible for the cognitive impairment.
Prevalence was 10.7% for CIND and 7.5% for ARCD, increased with age, and was higher in women. Age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.06-1.12), stroke (OR, 2.05; 95% CI, 1.26-3.35) and heart failure (OR, 1.73; 95% CI, 1.11-2.68) were significantly and positively associated with CIND at multivariate analysis. Education (OR, 0.61; 95% CI, 0.56-0.65) and smoking (OR, 0.72; 95% CI, 0.54-0.98) showed a negative correlation. Age and myocardial infarction were positively associated with ARCD, whereas a negative correlation was found for education and smoking. The effect of smoking was no more significant either on CIND or ARCD considering current habits or "pack year" exposure. CIND showed an independent impact on ADL (OR, 1.88; 95% CI, 1.41-2.49).
CIND is very frequent in older people. The effect of demographic variables and vascular conditions offers opportunities for prevention. The association with functional impairment is useful to evaluate the burden of disability and healthcare demands.
To evaluate the predictive utility of self-reported and informant-reported functional deficits in patients with mild cognitive impairment (MCI) for the follow-up diagnosis of probable AD.
The Pfeffer Functional Activities Questionnaire (FAQ) and Lawton Instrumental Activities of Daily Living (IADL) Scale were administered at baseline. Patients were followed at 6-month intervals, and matched normal control subjects (NC) were followed annually.
Self-reported deficits were higher for patients with MCI than for NC. At baseline, self- and informant-reported functional deficits were significantly greater for patients who converted to AD on follow-up evaluation than for patients who did not convert, even after controlling for age, education, and modified Mini-Mental State Examination scores. While converters showed significantly more informant- than self-reported deficits at baseline, nonconverters showed the reverse pattern. Survival analyses further revealed that informant-reported deficits (but not self-reported deficits) and a discrepancy score indicating greater informant- than self-reported functional deficits significantly predicted the development of AD. The discrepancy index showed high specificity and sensitivity for progression to AD within 2 years.
These findings indicate that in patients with MCI, the patient's lack of awareness of functional deficits identified by informants strongly predicts a future diagnosis of AD. If replicated, these findings suggest that clinicians evaluating MCI patients should obtain both self-reports and informant reports of functional deficits to help in prediction of long-term outcome.
Older people commonly present with memory loss although on assessment are not found to have a full dementia complex. Previous studies have suggested however that people with subjective and objective cognitive loss are at higher risk of dementia. We aimed to determine from the literature the rate of conversion from mild cognitive impairment to dementia.
Systematic review of MedLine, PsychLit and EmBase.
We identified 19 longitudinal studies published between 1991 and 2001 that addressed conversion of mild cognitive impairment to dementia. Overall the rate of conversion was 10% but with large differences between studies. The single biggest variable accounting for between study heterogeneity was source of subjects, with self-selected clinic attenders having the highest conversion rate. The most important factor accounting for heterogeneity within studies was cognitive testing, with poor performance predicting conversion with a high degree of accuracy.
These data strongly support the notion that subjective and objective evidence of cognitive decline is not normal and predicts conversion to dementia. The more stringent the measures of both variables the better the prediction of conversion. Mild cognitive impairment, appropriately diagnosed, is a good measure with which to select subjects for disease modification studies.
The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
Mild Cognitive Impairment (MCI) is a borderline state between age-associated cognitive decline and mild dementia. MCI is separated from mild dementia by an absence of global intellectual deterioration and the preservation of activities of daily living (ADL). However, even mild degrees of cognitive deterioration are known to have negative effects on complex ADL.
To examine whether patients with MCI have impaired ADL as compared to healthy controls, which areas of ADL are particularly involved, and whether limitations on ADL are associated with demographical or clinical data.
Forty-eight patients with MCI diagnosed according to research criteria and 42 cognitively unimpaired controls were enrolled. Cognitive function was inter alia assessed by the MMSE, complex ADL by the ADCS-MCI-ADL scale. Frequency distributions were compared between patients and controls using chi-square tests. Mean values were examined for statistically significant differences using Kruskal-Wallis tests. A Bonferroni correction for multiple comparisons was applied to the comparison of the 18 areas of the ADCS-MCI-ADL scale. Associations between ADL and biographical or clinical data were analysed using non-parametric correlations.
The overall score on the ADCS-MCI-ADL scale was significantly lower in the MCI group. Patients performed significantly worse on 14 out of 18 activities. Activities involving memory or complex reasoning were particularly impaired, whereas more basic activities were unimpaired. There were no statistically significant associations of the ADCS-MCI-ADL overall score with age, years of formal education, gender, or number of cognitive domains affected in the group of MCI patients. However, there was a statistically significant association between the ADCS-MCI-ADL and the MMSE score.
MCI patients may be impaired in complex ADL.
The purpose of the present study was to examine the types of impairments in everyday function that accompany mild cognitive impairment (MCI). Data for this study was collected from 434 individuals consecutively evaluated at a university-based Alzheimer's Center. A total of 96 participants were diagnosed with MCI, 105 were cognitively normal, and 233 had dementia. Informant ratings of participants' abilities were obtained across different functional domains reflecting everyday abilities related to memory, language, visual spatial abilities, planning, organization, and divided attention. As expected, the demented group was significantly more impaired than the healthy control and MCI groups across all of the functional domains. The MCI group also showed significantly more functional impairment relative to healthy controls in all of the functional domains. Examination of the effect sizes as a measure of the magnitude of functional impairment in the MCI groups relative to controls showed that the greatest degree of impairment occurred within the Everyday Memory domain. The current findings suggest that individuals with MCI demonstrate deficits in a wide range of everyday functions but that the magnitude of these changes is greatest for those functional abilities that rely heavily on memory.
A Clinical Task Force, composed of clinical leaders from Alzheimer's Disease Centers (ADC), was convened by the National Institute on Aging to develop a uniform set of assessment procedures to characterize individuals with mild Alzheimer disease and mild cognitive impairment in comparison with nondemented aging. The resulting Uniform Data Set (UDS) defines a common set of clinical observations to be collected longitudinally on ADC participants in accordance with standard methods. The UDS was implemented at all ADCs on September 1, 2005. Data obtained with the UDS are submitted to the National Alzheimer's Coordinating Center and represent a unique and valuable source of data to support and stimulate collaborative research.
Since widely accepted definitions of dementia encompass impairments in social and occupational, as well as cognitive, function, we investigated the diagnostic accuracy of Lawton and Brody's Instrumental Activities of Daily Living (IADL) Scale as an independent test for the diagnosis of dementia.
The IADL Scale was administered to consecutive referrals to 2 memory clinics over a 2-year period, independent of other tests (interview, neuropsychology, imaging) which were used to establish diagnoses according to standard diagnostic criteria, and the results were compared.
In a cohort of 296 patients, 52% adjudged to have dementia, IADL Scale scores and subscores showed low sensitivity, specificity, and positive and negative predictive values for the diagnosis of dementia. The likelihood ratios, a measure of diagnostic gain, were generally small to unimportant, and diagnostic accuracy as measured by area under the receiver operating characteristic curve was no better than 0.75.
IADL Scale scores are not very helpful in making a diagnosis of dementia. More sensitive scales may be required to detect dementia-related functional decline, although it is also possible that dementia syndromes may be present in the absence of functional decline, challenging accepted definitions of dementia.
To empirically validate the expanded concept of mild cognitive impairment (MCI), which differentiates between four clinical subtypes-amnestic MCI-single domain, amnestic MCI-multiple domains, nonamnestic MCI-single domain, and nonamnestic MCI-multiple domains-and to examine the prevalence, course, and outcome of these four clinical MCI subtypes.
We studied a community sample of 980 dementia-free individuals aged 75 years or older who participated in the Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants were examined by neuropsychological testing based on 6 years of observation. The diagnoses of the four clinical MCI subtypes were made according to the original and to slightly modified criteria by Petersen et al. (2001) (both with a cutoff of 1.0 SD and with a cutoff of 1.5 SD). The complete range of outcome types (dementia, death, improvement, stable diagnosis, unstable diagnosis) was described for all subtypes. The relative predictive power of stable MCI for dementia onset was determined.
MCI-single domain is more frequent than MCI-multiple domains, and the nonamnestic MCI type is as frequent as the amnestic MCI type. The "MCI modified, 1.0 SD" criteria have the highest relative predictive power for the development of dementia (sensitivity = 74%, specificity = 73%). Alzheimer disease (AD) was the most common type of dementia at follow-up in all but one MCI subtype. Participants with nonamnestic MCI-multiple domains were more likely to progress to a non-AD dementia.
It has been assumed that each MCI subtype is associated with an increased risk for a particular type of dementia. We can only partially agree with this.
Despite the fact that the current definitions of dementia in the DSM-IV and ICD-10 require functional deterioration for the diagnosis of dementia, it is not necessary a formal evaluation of functional capacity.
To examine the efficiency of functional assessment as a method of screening dementia in population studies.
This systematic review was based on information from MEDLINE, EMBASE, Index Médico Español (IME), and related articles. The studies included are population studies of patients over 65, in which normal and demented (established diagnosis) subjects are compared. In all of them, subjects were evaluated using the instrumental activities of daily living scale (IADL) as the method of screening for dementia.
Two thousand three hundred and three abstracts and bibliographical references were reviewed. The authors of the selected studies were contacted and asked about other ongoing studies or indexes not included in our review in order to complete a meta-analysis. Finally, five studies were selected (n = 11.960). A meta-analysis was performed, with a statistical Q* value of 0.88 (SE 0.26).
The functional assessment of the IADL showed an acceptable efficiency for the screening of dementia in the population studies included in this review, although few studies have verified this efficiency (sensitivity and specificity of the scales used). Further research is necessary in this field to be able to draw definitive conclusions.
To examine trajectories of change in everyday function for individuals with cognitive deficits suggestive of mild cognitive impairment (MCI).
Using data from the longitudinal, multisite Advanced Cognitive Training for Independent and Vital Elderly Study allowed for post hoc classification of MCI status at baseline using psychometric definitions for amnestic MCI, nonamnestic MCI, multidomain MCI, and no MCI.
Six U.S. cities.
Two thousand eight hundred thirty-two volunteers (mean age 74; 26% African American) living independently, recruited from senior housing, community centers, hospitals, and clinics.
Mixed-effect models examined changes in self-reported activities of daily living and instrumental activities of daily living (IADLs) from the Minimum Data Set Home Care Interview in 2,358 participants over a 3-year period.
In models for IADL performance, IADL difficulty, and a daily functioning composite, there was a significant time by MCI classification interaction for each MCI subtype, indicating that all MCI groups showed faster rates of decline in everyday function than cognitively normal participants with no MCI.
Results demonstrate the importance of MCI as a clinical entity that not only predicts progression to dementia, but also predicts functional declines in activities that are key to autonomy and quality of life. MCI classification guidelines should allow for functional changes in MCI, and clinicians should monitor for such changes. Preservation of function may serve as a meaningful outcome for intervention efforts.
The National Alzheimer's Coordinating Center (NACC) is responsible for developing and maintaining a database of participant information collected from the 29 Alzheimer's Disease Centers (ADCs) funded by the National Institute on Aging (NIA). The NIA appointed the ADC Clinical Task Force to determine and define an expanded, standardized clinical data set, called the Uniform Data Set (UDS). The goal of the UDS is to provide ADC researchers a standard set of assessment procedures, collected longitudinally, to better characterize ADC participants with mild Alzheimer disease and mild cognitive impairment in comparison with nondemented controls. NACC implemented the UDS (September 2005) by developing data collection forms for initial and follow-up visits based on Clinical Task Force definitions, a relational database, and a data submission system accessible by all ADCs. The NIA requires ADCs to submit UDS data to NACC for all their Clinical Core participants. Thus, the NACC web site (https://www.alz.washington.edu) was enhanced to provide efficient and secure access data submission and retrieval systems.
To examine incidence rates and antecedents of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among diverse elders without dementia at the initial visit, and to examine the characteristics of elders with MCI who reverted to normal on follow-up examination.
A total of 2,364 Caribbean Hispanic, black, or non-Hispanic white subjects, aged 65 or older, who were free of dementia at initial evaluation were followed up every 18 to 24 months. Incidence rate of MCI and AD was determined by examination of neurological, medical, psychiatric, and neuropsychological function.
Over 10,517 person-years, 21% of normal elderly subjects progressed to MCI (annual incidence rate, 5.1%; 95% confidence interval, 4.6-5.6%). Of those with MCI initially, 21.8% were subsequently diagnosed with AD (annual incidence rate, 5.4%; 95% confidence interval, 4.7-6.3%), 47% remained unchanged, and 31% reverted to normal. Those with MCI were 2.8 times more likely to experience development of AD than normal elderly subjects. MCI with impairment in memory and at least one other cognitive domain was associated with greatest risk for progression to AD and was also least likely to revert to normal at follow-up. Consistent diagnosis of MCI or incident probable or possible AD was 60% sensitive and 94% specific for the pathological diagnosis of AD.
Impaired memory and language were useful predictors of transition to AD. Reversion to normal from MCI was frequent, but those with impairment in more than one cognitive domain were more likely to progress or remain impaired than those with single-domain impairment. Clinical diagnosis of MCI does not always predict AD neuropathology.
To determine whether participants with mild cognitive impairment (MCI) differ from cognitively normal (NC) older adults on traditional and novel informant-based measures of activities of daily living (ADL) and to identify cognitive correlates of ADLs among participants with MCI.
Cross-sectional.
University medical setting.
Seventy-seven participants (NC: N = 39; MCI: N = 38), 60 to 90 years old (73.5 +/- 6.6 years; 53% female).
Neuropsychological and ADL measures.
Neuropsychological tests were administered to NC and MCI participants. Informants completed the Lawton and Brody Instrumental Activities of Daily Living and Physical Self-Maintenance Scale, including instrumental (IADL) and basic ADL (BADL) scales, as well as the Functional Capacities for Activities of Daily Living (FC-ADL), an error-based ADL measure.
No statistically or clinically significant between-group differences emerged for the BADL or IADL subscales. However, a robust difference was noted for the FC-ADL scale (MCI errors > NC errors; F((1,75))= 13.6, p <0.001; d = 0.84). Among MCI participants, correlations revealed that a measure of verbal learning was the only neuropsychological correlate of FC-ADL total score (r = -0.39, df = 36, p = 0.007). No neuropsychological measures were significantly associated with the IADL or BADL subscale score.
Traditional measures assessing global ADLs may not be sensitive to early functional changes related to MCI; however, error-based measures may capture the subtle evolving functional decline associated with MCI. Among MCI participants, early functional difficulties are associated with verbal learning performance, possibly secondary to the hallmark cognitive impairment associated with this cohort.
Diagnostic accuracy of a screening protocol in the diagnosis of dementia: the NEDICES study
- D Munoz
- Fp Bermejo
- R Trincado
Munoz D, Bermejo FP, Trincado R, et al. Diagnostic accuracy of a screening protocol in the diagnosis of dementia: the NEDICES study. Neuroepidemiology 2001;20:217–218.
Diagnostic accuracy of a screening protocol in the diagnosis of dementia: the NEDICES study.
- Munoz