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The impact of amyloid-beta and tau on prospective cognitive decline in older individuals.

ABSTRACT: OBJECTIVES:Amyloid-beta (A?) and tau pathologies are commonly observed among clinically normal older individuals at postmortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated. METHODS:One hundred thirty-seven older individuals (age = 76.3 ± 6.22 years) participating in the Harvard Aging Brain Study underwent A? (11 C-Pittsburgh compound B) and tau (18 F-flortaucipir) positron emission tomography (PET) with prospective neuropsychological assessments following PET imaging (mean number of cognitive visits = 2.8 ± 1.1). Tau and A? PET measures were assessed in regions of interest (ROIs) as well as vertex-wise map analyses. Cognitive change was evaluated with Memory and Executive Function composites. RESULTS:Higher levels of A? and tau were both associated with greater memory decline, but not with change in executive function. Higher cortical A? was associated with higher tau levels in all ROIs, independent of age, and very elevated levels of tau were observed primarily in clinically normal with elevated A?. A significant interaction between tau and A? was observed in both ROI and map-level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies. INTERPRETATION:Our results are consistent with the supposition that both A? and tau are necessary for memory decline in the preclinical stages of AD. These findings may be relevant for disambiguating aging and early cognitive manifestations of AD, and to inform secondary prevention trials in preclinical AD. Ann Neurol 2019;00:1-3 ANN NEUROL 2019;85:181-193.

SUBMITTER: Sperling RA

PROVIDER: S-EPMC6402593 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The impact of amyloid-beta and tau on prospective cognitive decline in older individuals.

Sperling Reisa A RA Mormino Elizabeth C EC Schultz Aaron P AP Betensky Rebecca A RA Papp Kathryn V KV Amariglio Rebecca E RE Hanseeuw Bernard J BJ Buckley Rachel R Chhatwal Jasmeer J Hedden Trey T Marshall Gad A GA Quiroz Yakeel T YT Donovan Nancy J NJ Jackson Jonathan J Gatchel Jennifer R JR Rabin Jennifer S JS Jacobs Heidi H Yang Hyun-Sik HS Properzi Michael M Kirn Dylan R DR Rentz Dorene M DM Johnson Keith A KA

Annals of neurology 20190121 2

<h4>Objectives</h4>Amyloid-beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at postmortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated.<h4>Methods</h4>One hundred thirty-seven older individuals (age = 76.3 ± 6.22 years) participating in the Harvard Aging Brain Study un ...[more]

PMID: 30549303

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Project description:BackgroundStage 1 of the National Institute on Aging-Alzheimer's Association's proposed Alzheimer's disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ.MethodsWe examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer's Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology.ResultsForty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level).ConclusionsThe possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels.

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Dataset Information

The impact of amyloid-beta and tau on prospective cognitive decline in older individuals.

Publications

The impact of amyloid-beta and tau on prospective cognitive decline in older individuals.

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