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Latent class analysis identifies functional decline with Amsterdam IADL in preclinical Alzheimer's disease.

ABSTRACT: Introduction:Trials in Alzheimer's disease (AD) now include participants at the earliest stages to prevent further decline. However, the lack of tools sensitive to subtle functional changes in early-stage AD hinders the development of new therapies as it is difficult to prove their clinical relevance. Methods:We assessed functional changes over three years in 289 elderly memory complainers from the Investigation of Alzheimer's Predictors in subjective memory complainers cohort using the Amsterdam Instrumental-Activities-of-Daily-Living questionnaire (A-IADL-Q). Results:No overall functional decline related to AD imaging markers was evidenced. However, five distinct classes of A-IADL-Q trajectories were identified. The largest class (212 [73.4%]) had stable A-IADL-Q scores over 3 years. A second group (23 [8.0%]) showed a persistent functional decline, higher amyloid load (P = .0005), and lower education (P = .0392). Discussion:The A-IADL-Q identified a subtle functional decline in asymptomatic at-risk AD individuals. This could have important implications in the field of early intervention in AD.

SUBMITTER: Villeneuve SC

PROVIDER: S-EPMC6804616 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Latent class analysis identifies functional decline with Amsterdam IADL in preclinical Alzheimer's disease.

Villeneuve Sarah-Christine SC Houot Marion M Cacciamani Federica F Verrijp Merike M Dubois Bruno B Sikkes Sietske S Epelbaum Stéphane S

Alzheimer's & dementia (New York, N. Y.) 20191008

<h4>Introduction</h4>Trials in Alzheimer's disease (AD) now include participants at the earliest stages to prevent further decline. However, the lack of tools sensitive to subtle functional changes in early-stage AD hinders the development of new therapies as it is difficult to prove their clinical relevance.<h4>Methods</h4>We assessed functional changes over three years in 289 elderly memory complainers from the Investigation of Alzheimer's Predictors in subjective memory complainers cohort usi ...[more]

PMID: 31650012

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Project description:An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function.

Project description:ObjectiveCommonly used measures of instrumental activities of daily living (IADL) do not capture activities for a technologically advancing society. This study aimed to adapt the proxy/informant-based Amsterdam IADL Questionnaire (A-IADL-Q) for use in the UK and develop a self-report version.DesignAn iterative mixed method cross-cultural adaptation of the A-IADL-Q and the development of a self-report version involving a three-step design: (1) interviews and focus groups with lay and professional stakeholders to assess face and content validity; (2) a questionnaire to measure item relevance to older adults in the U.K.; (3) a pilot of the adapted questionnaire in people with cognitive impairment.SettingCommunity settings in the UK.ParticipantsOne hundred and forty-eight participants took part across the three steps: (1) 14 dementia professionals; 8 people with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia due to Alzheimer's disease; and 6 relatives of people with MCI or dementia; (2) 92 older adults without cognitive impairment; and (3) 28 people with SCD or MCI.MeasurementsThe cultural relevance and applicability of the A-IADL-Q scale items were assessed using a 6-point Likert scale. Cognitive and functional performance was measured using a battery of cognitive and functional measures.ResultsIterative modifications to the scale resulted in a 55-item adapted version appropriate for UK use (A-IADL-Q-UK). Pilot data revealed that the new and revised items performed well. Four new items correlated with the weighted average score (Kendall's Tau -.388, -.445, -.497, -.569). An exploratory analysis of convergent validity found correlations in the expected direction with cognitive and functional measures.ConclusionThe A-IADL-Q-UK provides a measurement of functional decline for use in the UK that captures culturally relevant activities. A new self-report version has been developed and is ready for testing. Further evaluation of the A-IADL-Q-UK for construct validity is now needed.

Project description:Alzheimer's disease (AD) is the most common form of dementia. Obesity in middle age increases AD risk and severity, which is alarming given that obesity prevalence peaks at middle age and obesity rates are accelerating worldwide. Midlife, but not late-life obesity increases AD risk, suggesting that this interaction is specific to preclinical AD. AD pathology begins in middle age, with accumulation of amyloid beta (Aβ), hyperphosphorylated tau, metabolic decline, and neuroinflammation occurring decades before cognitive symptoms appear. We used a transcriptomic discovery approach in young adult (6.5 months old) male and female TgF344-AD rats that overexpress mutant human amyloid precursor protein and presenilin-1 and wild-type (WT) controls to determine whether inducing obesity with a high-fat/high-sugar “Western” diet during preclinical AD increases brain metabolic dysfunction in dorsal hippocampus (dHC), a brain region vulnerable to the effects of obesity and early AD. Analyses of dHC gene expression data showed dysregulated mitochondrial and neurotransmission pathways, and up-regulated genes involved in cholesterol synthesis. Western diet amplified the number of genes that were different between AD and WT rats and added pathways involved in noradrenergic signaling, dysregulated inhibition of cholesterol synthesis, and decreased intracellular lipid transporters. Importantly, the Western diet impaired dHC-dependent spatial working memory in AD but not WT rats, confirming that the dietary intervention accelerated cognitive decline. To examine later consequences of early transcriptional dysregulation, we measured dHC monoamine levels in older (13 months old) AD and WT rats of both sexes after long-term chow or Western diet consumption. Norepinephrine (NE) abundance was significantly decreased in AD rats, NE turnover was increased, and the Western diet attenuated the AD-induced increases in turnover. Collectively, these findings indicate obesity during prodromal AD impairs memory, potentiates AD-induced metabolic decline likely leading to an overproduction of cholesterol, and interferes with compensatory increases in NE transmission.

Dataset Information

Latent class analysis identifies functional decline with Amsterdam IADL in preclinical Alzheimer's disease.

Publications

Latent class analysis identifies functional decline with Amsterdam IADL in preclinical Alzheimer's disease.

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