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Regional 18F-Fluorodeoxyglucose Hypometabolism is Associated with Higher Apathy Scores Over Time in Early Alzheimer Disease.

ABSTRACT: OBJECTIVES:Apathy is among the earliest and most pervasive neuropsychiatric symptoms in prodromal and mild Alzheimer disease (AD) dementia that correlates with functional impairment and disease progression. We investigated the association of apathy with regional 18F-fluorodeoxyglucose (FDG) metabolism in cognitively normal, mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative database. DESIGN:Cross-sectional and longitudinal studies. SETTING:57 North American research sites. PARTICIPANTS:402 community dwelling elders. MEASUREMENTS:Apathy was assessed using the Neuropsychiatric Inventory Questionnaire. Baseline FDG metabolism in five regions implicated in the neurobiology of apathy and AD was investigated in relationship to apathy at baseline (cross-sectional general linear model) and longitudinally (mixed random/fixed effect model). Covariates included age, sex, diagnosis, apolipoprotein E genotype, premorbid intelligence, cognition, and antidepressant use. RESULTS:Cross-sectional analysis revealed that posterior cingulate hypometabolism, diagnosis, male sex, and antidepressant use were associated with higher apathy scores. Longitudinal analysis revealed that the interaction of supramarginal hypometabolism and time, posterior cingulate hypometabolism, and antidepressant use were associated with higher apathy scores across time; only supramarginal hypometabolism was positively related to rate of increase of apathy. CONCLUSIONS:Results support an association of apathy with hypometabolism in parietal regions commonly affected in early stages of AD, rather than medial frontal regions implicated in the neurobiology of apathy in later stages. Further work is needed to substantiate whether this localization is specific to apathy rather than to disease stage, and to investigate the potential role of AD proteinopathies in the pathogenesis of apathy.

SUBMITTER: Gatchel JR

PROVIDER: S-EPMC5906700 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Regional 18F-Fluorodeoxyglucose Hypometabolism is Associated with Higher Apathy Scores Over Time in Early Alzheimer Disease.

Gatchel Jennifer R JR Donovan Nancy J NJ Locascio Joseph J JJ Becker J Alex JA Rentz Dorene M DM Sperling Reisa A RA Johnson Keith A KA Marshall Gad A GA

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20170104 7

<h4>Objectives</h4>Apathy is among the earliest and most pervasive neuropsychiatric symptoms in prodromal and mild Alzheimer disease (AD) dementia that correlates with functional impairment and disease progression. We investigated the association of apathy with regional 18F-fluorodeoxyglucose (FDG) metabolism in cognitively normal, mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative database.<h4>Design</h4>Cross-sectional and longitudinal stud ...[more]

PMID: 28410856

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Project description:In its original form, the amyloid cascade hypothesis of Alzheimer's disease holds that fibrillar deposits of amyloid are an early, driving force in pathological events leading ultimately to neuronal death. Early clinicopathological investigations highlighted a number of inconsistencies leading to an updated hypothesis in which amyloid plaques give way to amyloid oligomers as the driving force in pathogenesis. Rather than focusing on the inconsistencies, amyloid imaging studies have tended to highlight the overlap between regions that show early amyloid plaque signal on positron emission tomography and that also happen to be affected early in Alzheimer's disease. Recent imaging studies investigating the regional dependency between metabolism and amyloid plaque deposition have arrived at conflicting results, with some showing regional associations and other not. We extracted multimodal neuroimaging data from the Alzheimer's disease neuroimaging database for 227 healthy controls and 434 subjects with mild cognitive impairment. We analysed regional patterns of amyloid deposition, regional glucose metabolism and regional atrophy using florbetapir ((18)F) positron emission tomography, (18)F-fluordeoxyglucose positron emission tomography and T1-weighted magnetic resonance imaging, respectively. Specifically, we derived grey matter density and standardized uptake value ratios for both positron emission tomography tracers in 404 functionally defined regions of interest. We examined the relation between regional glucose metabolism and amyloid plaques using linear models. For each region of interest, correcting for regional grey matter density, age, education and disease status, we tested the association of regional glucose metabolism with (i) cortex-wide florbetapir uptake; (ii) regional (i.e. in the same region of interest) florbetapir uptake; and (iii) regional florbetapir uptake while correcting in addition for cortex-wide florbetapir uptake. P-values for each setting were Bonferroni corrected for 404 tests. Regions showing significant hypometabolism with increasing cortex-wide amyloid burden were classic Alzheimer's disease-related regions: the medial and lateral parietal cortices. The associations between regional amyloid burden and regional metabolism were more heterogeneous: there were significant hypometabolic effects in posterior cingulate, precuneus, and parietal regions but also significant positive associations in bilateral hippocampus and entorhinal cortex. However, after correcting for global amyloid burden, few of the negative associations remained and the number of positive associations increased. Given the wide-spread distribution of amyloid plaques, if the canonical cascade hypothesis were true, we would expect wide-spread, cortical hypometabolism. Instead, cortical hypometabolism appears to be linked to global amyloid burden. Thus we conclude that regional fibrillar amyloid deposition has little to no association with regional hypometabolism.

Project description:Background/objectivesPopulation-based incidence estimates of dementia and Alzheimer disease (AD) provide important information for public health policy and resource allocation. We conducted a meta-analysis of published studies that reported age-specific incidence rates of dementia and AD to determine whether dementia and AD incidence rates are changing over time.DesignPubMed and MEDLINE were searched for publications through June 30, 2017, using key words "dementia", "Alzheimer", and "incidence." Inclusion criteria for the meta-analysis are: (1) population-based studies using personal interviews and direct examinations of the study subjects, (2) standardized clinical diagnosis criteria, (3) reporting age-specific incidence rates, (4) published in English, and (5) sample size of 500 or greater and length of follow-up of 2 years or greater. Mixed-effects models were used to determine the association between birth year and incidence rates.MeasurementsAge-specific dementia/AD incidence rates and their standard errors reported in each study.ResultsThirty-eight articles with 53 cohorts on dementia incidence and 31 articles with 35 cohorts on AD incidence met the inclusion criteria. There were significant associations between later birth years and decreased dementia incidence rates in all three age groups (65-74, 75-84, and 85 years and older). There were no significant associations between birth year and AD incident rates in any of the three age groups. In particular, AD incidence rates reported from Western countries stayed steady in all age groups, while studies in non-Western countries showed significantly increased AD incidence rates for the 65 to 74 years age group (odds ratio = 2.78; P = .04), but a nonsignificant association for the 75 to 84 or 85 years and older groups.ConclusionDementia incidence declined over the past four decades, but AD incidence did not decline. Further research, especially from non-Western countries, is needed to elucidate the mechanism underlying the trends in dementia and AD incidence over time.

Dataset Information

Regional 18F-Fluorodeoxyglucose Hypometabolism is Associated with Higher Apathy Scores Over Time in Early Alzheimer Disease.

Publications

Regional 18F-Fluorodeoxyglucose Hypometabolism is Associated with Higher Apathy Scores Over Time in Early Alzheimer Disease.

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