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.

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Available from: Lauren Wadsworth, Dec 15, 2013
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    • "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. "
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    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.
    Journal of Alzheimer's disease: JAD 09/2015; 47(2):421-432. DOI:10.3233/JAD-150146 · 4.15 Impact Factor
    • "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. "
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    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.
    Clinical Neurology and Neurosurgery 05/2015; 135:27-33. DOI:10.1016/j.clineuro.2015.05.010 · 1.13 Impact Factor
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    • "Around 35–75% MCI (Apostolova and Cummings, 2008) and 75% of AD patients experience emotional symptoms, with depression and anxiety as the most common ones during the prodromal disease stage (Sturm et al., 2013). The most frequently observed neuropsychiatric features in MCI individuals are apathy, depression, anxiety, irritability, whereas in AD patients apart from these same symptoms agitation/aggression is also present (Lyketsos et al., 2002; Wadsworth et al., 2012; Dillon et al., 2013). It has been noticed that these symptoms often precede and accelerate conversion to dementia (Apostolova and Cummings, 2008; Wadsworth et al., 2012; Dillon et al., 2013). "
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    ABSTRACT: The hippocampus is one of the earliest affected brain regions in Alzheimer's disease (AD) and its dysfunction is believed to underlie the core feature of the disease-memory impairment. Given that hippocampal volume is one of the best AD biomarkers, our review focuses on distinct subfields within the hippocampus, pinpointing regions that might enhance the predictive value of current diagnostic methods. Our review presents how changes in hippocampal volume, shape, symmetry and activation are reflected by cognitive impairment and how they are linked with neurogenesis alterations. Moreover, we revisit the functional differentiation along the anteroposterior longitudinal axis of the hippocampus and discuss its relevance for AD diagnosis. Finally, we indicate that apart from hippocampal subfield volumetry, the characteristic pattern of hippocampal hyperactivation associated with seizures and neurogenesis changes is another promising candidate for an early AD biomarker that could become also a target for early interventions.
    Frontiers in Cellular Neuroscience 03/2014; 8:95. DOI:10.3389/fncel.2014.00095 · 4.29 Impact Factor
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