Dataset Information

Odor identification and Alzheimer disease biomarkers in clinically normal elderly.

ABSTRACT:

Objectives

Our objective was to investigate cross-sectional associations between odor identification ability and imaging biomarkers of neurodegeneration and amyloid deposition in clinically normal (CN) elderly individuals, specifically testing the hypothesis that there may be an interaction between amyloid deposition and neurodegeneration in predicting odor identification dysfunction.

Methods

Data were collected on 215 CN participants from the Harvard Aging Brain Study. Measurements included the 40-item University of Pennsylvania Smell Identification Test and neuropsychological testing, hippocampal volume (HV) and entorhinal cortex (EC) thickness from MRI, and amyloid burden using Pittsburgh compound B (PiB) PET. A linear regression model with backward elimination (p < 0.05 retention) evaluated the cross-sectional association between the University of Pennsylvania Smell Identification Test and amyloid burden, HV, and EC thickness, assessing for effect modification by PiB status. Covariates included age, sex, premorbid intelligence, APOE ?4 carrier status, and Boston Naming Test.

Results

In unadjusted univariate analyses, worse olfaction was associated with decreased HV (p < 0.001), thinner EC (p = 0.003), worse episodic memory (p = 0.03), and marginally associated with greater amyloid burden (binary PiB status, p = 0.06). In the multivariate model, thinner EC in PiB-positive individuals (interaction term) was associated with worse olfaction (p = 0.02).

Conclusions

In CN elderly, worse odor identification was associated with markers of neurodegeneration. Furthermore, individuals with elevated cortical amyloid and thinner EC exhibited worse odor identification, elucidating the potential contribution of olfactory testing to detect preclinical AD in CN individuals.

SUBMITTER: Growdon ME

PROVIDER: S-EPMC4451046 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Publications

Odor identification and Alzheimer disease biomarkers in clinically normal elderly.

Growdon Matthew E ME Schultz Aaron P AP Dagley Alexander S AS Amariglio Rebecca E RE Hedden Trey T Rentz Dorene M DM Johnson Keith A KA Sperling Reisa A RA Albers Mark W MW Marshall Gad A GA

Neurology 20150501 21

<h4>Objectives</h4>Our objective was to investigate cross-sectional associations between odor identification ability and imaging biomarkers of neurodegeneration and amyloid deposition in clinically normal (CN) elderly individuals, specifically testing the hypothesis that there may be an interaction between amyloid deposition and neurodegeneration in predicting odor identification dysfunction.<h4>Methods</h4>Data were collected on 215 CN participants from the Harvard Aging Brain Study. Measuremen ...[more]

PMID: 25934852

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Project description:A substantial proportion of clinically normal (CN) older individuals are classified as having suspected non-Alzheimer disease pathophysiology (SNAP), defined as biomarker negative for ?-amyloid (A?-) but positive for neurodegeneration (ND+). The etiology of SNAP in this population remains unclear.To determine whether CN individuals with SNAP show evidence of early Alzheimer disease (AD) processes (ie, elevated tau levels and/or increased risk for cognitive decline).This longitudinal observational study performed in an academic medical center included 247 CN participants from the Harvard Aging Brain Study. Participants were classified into preclinical AD stages using measures of A? (Pittsburgh Compound B [PIB]-labeled positron emission tomography) and ND (hippocampal volume or cortical glucose metabolism from AD-vulnerable regions). Classifications included stages 0 (A?-/ND-), 1 (A?+/ND-), and 2 (A?+/ND+) and SNAP (A?-/ND+). Continuous levels of PiB and ND, tau levels in the medial and inferior temporal lobes, and longitudinal cognition were examined. Data collection began in 2010 and is ongoing. Data were analyzed from 2015 to 2016.Evidence of amyloid-independent tau deposition and/or cognitive decline.Of the 247 participants (142 women [57.5%]; 105 men [42.5%]; mean age, 74 [range, 63-90] years), 64 (25.9%) were classified as having SNAP. Compared with the stage 0 group, the SNAP group was not more likely to have subthreshold PiB values (higher values within the A?- range), suggesting that misclassification due to the PiB cutoff was not a prominent contributor to this group (mean [SD] distribution volume ratio, 1.08 [0.05] for the SNAP group; 1.09 [0.05] for the stage 1 group). Tau levels in the medial and inferior temporal lobes were indistinguishable between the SNAP and stage 0 groups (entorhinal cortex, ??=?-0.005 [SE, 0.036]; parahippocampal gyrus, ??=?-0.001 [SE, 0.027]; and inferior temporal lobe, ??=?-0.004 [SE, 0.027]; P???.88) and were lower in the SNAP group compared with the stage 2 group (entorhinal cortex, ??=?-0.125 [SE, 0.041]; parahippocampal gyrus, ??=?-0.074 [SE, 0.030]; and inferior temporal lobe, ??=?-0.083 [SE, 0.031]; P???.02). The stage 2 group demonstrated greater cognitive decline compared with all other groups (stage 0, ??=?-0.239 [SE, 0.042]; stage 1, ??=?-0.242 [SE, 0.051]; and SNAP, ??=?-0.157 [SE, 0.044]; P???.001), whereas the SNAP group showed a diminished practice effect over time compared with the stage 0 group (??=?-0.082 [SE, 0.037]; P?=?.03).In this study, clinically normal adults with SNAP did not exhibit evidence of elevated tau levels, which suggests that this biomarker construct does not represent amyloid-independent tauopathy. At the group level, individuals with SNAP did not show cognitive decline but did show a diminished practice effect. SNAP is likely heterogeneous, with a subset of this group at elevated risk for short-term decline. Future refinement of biomarkers will be necessary to subclassify this group and determine the biological correlates of ND markers among A?- CN individuals.

Project description:OBJECTIVE:To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. METHODS:We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC-tau) from tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC- ) versus CMC > 0 (CMC+ ) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects. RESULTS:CMC+ participants had significantly greater neurodegeneration than CMC- participants but did not differ by amyloid or ERC-tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC-tau. INTERPRETATION:Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706-718.

Dataset Information

Odor identification and Alzheimer disease biomarkers in clinically normal elderly.

Objectives

Methods

Results

Conclusions

Publications

Odor identification and Alzheimer disease biomarkers in clinically normal elderly.

Similar Datasets

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