Neuropsychiatric Symptoms and Global Functional Impairment along the Alzheimer's Continuum

Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 3.55). 08/2012; 34(2):96-111. DOI: 10.1159/000342119
Source: PubMed


Neuropsychiatric symptoms in Alzheimer's disease (AD) are highly prevalent. We sought to determine whether neuropsychiatric symptoms were related to global functional impairment at baseline and over a 3-year period in older normal control (NC), mild cognitive impairment (MCI) and mild AD dementia subjects.

Eight hundred and twelve subjects (229 NC, 395 MCI, 188 AD) from the Alzheimer's Disease Neuroimaging Initiative study underwent cognitive and behavioral assessments over 3 years.

Greater hallucinations, anxiety and apathy were associated with greater global functional impairment at baseline, while the presence of hallucinations and apathy at baseline was associated with greater global functional impairment over time across all subjects. The following neuropsychiatric symptoms were not significantly associated with global functioning: delusions, agitation, depression, euphoria, disinhibition, irritability, aberrant motor behaviors, sleep and appetite.

These results suggest that increased baseline hallucinations, apathy and anxiety are associated with current and future disease progression in AD.

Download full-text


Available from: Lauren Wadsworth, Dec 15, 2013
  • Source
    • "Depressive symptoms are associated with poorer performance on activities of daily living (ADL) in community-dwelling and institutionalized older adults (Nyunt et al., 2012;Tomita and Burns, 2013;de Paula et al., 2015a), and are important predictors of functional status in MCI subjects (Bombin et al., 2012). The presence of cognitive impairment and comorbid depressive symptoms seems to lead to worse functional outcomes (Wadsworth et al., 2012). On the other hand, different studies did not find a significant association between depressive symptoms and functional status along the normal aging (NA)—MCI—AD continuum (Reppermund et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimer’s disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N=274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum.
    Full-text · Article · Jan 2016 · Frontiers in Psychology
  • Source
    • "Taken in aggregate, these prior studies of self and informant-reported cognitive and functional symptoms appear to parallel the findings of the current study of apathy, wherein CN individuals reported greater severity of apathy over time compared to informant or clinician report of apathy, while individuals with MCI at baseline reported lower apathy severity compared to informants and clinicians. Prior cross-sectional and longitudinal studies have shown that apathy is greater in those with greater AD severity, ranging from MCI to severe dementia, and that apathy worsens as AD progresses over time [3] [4] [14] [19] [66]. In the current study, we also showed that apathy measured in various fashions worsens over time in individuals at risk for AD due to MCI or old age. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Apathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Detecting apathy accurately may facilitate earlier diagnosis of AD. The Apathy Evaluation Scale (AES) is a promising tool for measurement of apathy in prodromal and possibly preclinical AD. Objective: To compare the three AES sub-scales- subject-reported (AES-S), informant-reported (AES-I), and clinician-reported (AES-C)- over time in individuals at risk for AD due to MCI and advanced age (cognitively normal [CN] elderly). Methods: Mixed effects longitudinal models were used to assess predictors of score for each AES sub-scale. Cox proportional hazards models were used to assess which AES sub-scales predict progression from MCI to AD dementia. Results: Fifty-seven MCI and 18 CN subjects (ages 53-86) were followed for 1.4 ± 1.2 years and 0.7 ± 0.7 years, respectively. Across the three mixed effects longitudinal models, the common findings were associations between greater apathy and greater years in study, a baseline diagnosis of MCI (compared to CN), and male gender. CN elderly self-reported greater apathy compared to that reported by informants and clinicians, while individuals with MCI under-reported their apathy compared to informants and clinicians. Of the three sub-scales, the AES-C best predicted transition from MCI to AD dementia. Conclusion: In a sample of CN elderly and elderly with MCI, apathy increased over time, particularly in men and those with MCI. AES-S scores may be more sensitive than AES-I and AES-C scores in CN elderly, but less reliable if subjects have MCI. Moreover, the AES-C sub-scale predicted progression from MCI to AD dementia.
    Full-text · Article · Sep 2015 · Journal of Alzheimer's disease: JAD
    • "Neuropsychiatric symptoms impact rates of cognitive decline and caregiver distress [1] [2], but these effects are hardly measurable . Functionality usually follows cognitive test performance; yet again this is a seldom objectively reconnoitred matter. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Primarily, we sought to verify correlations among assessments for cognition, behaviour and functional independence in a sample of patients with dementia due to Alzheimer's disease (AD). Secondarily, impacts of education, APOE haplotypes, length of dementia, age and alcohol use over the neuropsychiatric assessment were estimated. Patients with AD were assessed for demographic features, neuropsychiatric symptoms, cognitive test scores, functional impairment, caregiver burden and APOE haplotypes. Statistical comparisons were undertaken by way of Kruskal-Wallis test, linear regressions and Spearman correlations, significance at ρ<0.05. A total of 217 patients were included. Mean schooling was 4.21±3.7 years, with significant impacts over cognitive tests. Mean age at examination was 78±6.19 years-old, significantly influencing instrumental functionality. The mean length of the dementia syndrome was 5.4±2.9 years, significantly impacting cognitive decline and functionality. Apathy was the most common behavioural symptom, negatively correlated with anxiety and delusions, and positively correlated with lifetime alcohol load. Patients with previous smoking or drinking habits were more likely to continue smoking or drinking later in life. APOE4+ haplotypes led to earlier dementia onset and significantly lower caregiver burden in mild dementia stages. Most correlations among test results were highly significant, confirming that cognition, behaviour and functionality are usually interrelated in all stages of AD. Caregiver burden was correlated with behaviour, but not with cognition, and was lower for patients with APOE4+ haplotypes in mild dementia stages. Education is a major impact factor for cognitive performance. Copyright © 2015 Elsevier B.V. All rights reserved.
    No preview · Article · May 2015 · Clinical Neurology and Neurosurgery
Show more