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

ABSTRACT Background/aims:
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 Page Wadsworth, Dec 15, 2013
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    • "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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    • "Similarly, only studies examining for associations between putative biomarkers and global measures of cognition, rather than individual neuropsychological tests were included. Furthermore, studies solely examining for associations between biomarkers and measures of neuropsychiatric impairment were not included, as depression and behavioural disturbance are not clearly associated with disease progression in Alzheimer's disease [17]. "
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    ABSTRACT: Background Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson’s disease (PD) exist. Methods MEDLINE and EMBASE (1950–2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. Results 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality - cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. Conclusion We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional ‘roadmap’ for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.
    BMC Neurology 04/2013; 13(1):35. DOI:10.1186/1471-2377-13-35 · 2.04 Impact Factor
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