Dataset Information

Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults.

ABSTRACT: The ability to accurately judge memory efficiency (meta-memory monitoring) for newly learned (episodic) information, is decreased in older adults and even worse in Alzheimer's disease (AD), whereas no differences have been found for semantic meta-memory. The pathological substrates of this phenomenon are poorly understood. Here, we examine the association between meta-memory monitoring for episodic and semantic information to the two major proteinopathies in AD: amyloid (Aβ) and tau pathology in a group of cognitively unimpaired older adults. All participants underwent multi-tracer PET and meta-memory monitoring was assessed using a feeling-of-knowing (FOK) task for non-famous (episodic) and famous (semantic) face-name pairs. Whole brain voxel-wise correlations between meta-memory and PET data were conducted (controlling for memory), as well as confirmatory region-of-interest analyses. Participants had reduced episodic FOK compared to semantic FOK. Decreased episodic FOK was related to tauopathy in the medial temporal lobe regions, including the entorhinal cortex and temporal pole, whereas decreased semantic FOK was related to increased tau in regions associated with the semantic knowledge network. No association was found with Aβ-pathology. Alterations in the ability to accurately judge memory efficiency (in the absence of memory decline) may be a sensitive clinical indicator of AD pathophysiology in the pre-symptomatic phase.

SUBMITTER: Vannini P

PROVIDER: S-EPMC6879982 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults.

Vannini Patrizia P d'Oleire Uquillas Federico F Jacobs Heidi I L HIL Sepulcre Jorge J Gatchel Jennifer J Amariglio Rebecca E RE Hanseeuw Bernard B Papp Kathryn V KV Hedden Trey T Rentz Dorene M DM Pascual-Leone Alvaro A Johnson Keith A KA Sperling Reisa A RA

NeuroImage. Clinical 20191118

The ability to accurately judge memory efficiency (meta-memory monitoring) for newly learned (episodic) information, is decreased in older adults and even worse in Alzheimer's disease (AD), whereas no differences have been found for semantic meta-memory. The pathological substrates of this phenomenon are poorly understood. Here, we examine the association between meta-memory monitoring for episodic and semantic information to the two major proteinopathies in AD: amyloid (Aβ) and tau pathology in ...[more]

PMID: 31795044

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Project description:ObjectiveResearch in animals has shown that chronic stress exacerbates tau pathology. In humans, psychological stress has been associated with higher risk of Alzheimer disease clinical syndrome. The objective of this cross-sectional study was to assess the hypothesis that stress coping ability (assessed via the Brief Resilience Scale [BRS]) is associated with tau burden and to evaluate whether these associations differed by sex and amyloid status (A+/A-) in cognitively unimpaired (CU) older adults.MethodsWe included 225 CU participants (mean age 70.4 ± 10.2 years, 48% female) enrolled in the population-based Mayo Clinic Study of Aging who completed the BRS and underwent amyloid-PET (Pittsburgh compound B-PET) and tau-PET (AV1451-PET). We fitted multiple regression and analysis of covariance models to assess the associations between BRS and tau-PET and the interaction with amyloid status and sex. We focused on entorhinal cortex (ERC) tau burden and also performed voxel-wise analyses. Age, sex, education, depression, and anxiety were considered as covariates.ResultsHigher stress coping ability was associated with lower tau burden in the medial temporal lobe (including ERC) and occipito-temporal and cuneal/precuneal cortices. The association was present in both A+ and A- but weaker in A- CU older adults. There was an interaction between amyloid status and stress coping ability that was restricted to the medial temporal lobe tau such that A+ CU older adults with lower stress coping abilities showed higher tau. There were no significant interactions between stress coping and sex.ConclusionsA faster termination of the stress response (higher coping ability) may limit the negative effects of stress on tau deposition. Conversely, lower stress coping ability may be an early sign of accumulating tau pathology. Longitudinal studies are warranted to clarify whether stress mechanisms act to exacerbate tau pathology or tau influences stress-related brain mechanisms and lowers the ability to cope with stress.

Project description:ImportanceTo reduce the rising incidence of clinical impairment due to Alzheimer disease, it is essential to define older adults at highest risk. Widowhood may be an unrecognized factor contributing to accelerated clinical progression along the Alzheimer disease pathway among cognitively unimpaired older adults.ObjectiveTo determine whether widowhood status and level of brain β-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults.Design, setting, and participantsIn this cohort study, 257 married, widowed, and unmarried (ie, never married, divorced, or separated) participants from the Harvard Aging Brain Study longitudinal cohort underwent baseline evaluation of neocortical β-amyloid levels using Pittsburgh compound B positron emission tomography and 4 annual cognitive assessments. Data were collected from September 2010 to February 2017 and analyzed from July 2018 to July 2019.Main outcomes and measuresCognitive performance was measured using the Preclinical Alzheimer Cognitive Composite.ResultsOf the 257 participants, 153 (59.5%) were women, and the mean (SD) age was 73.5 (6.1) years; 145 participants (56.4%) were married (66 [45.5%] women), 77 (30.0%) were unmarried (56 [72.7%] women), and 35 (13.6%) were widowed (31 [88.6%] women). Compared with married participants, widowed participants demonstrated worsening cognitive performance after adjusting for age, sex, socioeconomic status, depression, and β-amyloid levels (β = -0.11; 95% CI, -0.19 to -0.04; P = .002) with no difference observed between married and unmarried participants. Furthermore, widowed participants with higher baseline β-amyloid levels exhibited steeper cognitive decline (β = -0.22; 95% CI, -0.42 to -0.03; P = .02), indicating both independent and interactive associations of β-amyloid levels and widowhood with cognition. In a secondary model using dichotomous β-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high β-amyloid was nearly 3 times faster than among married participants with high β-amyloid (widowed, high β-amyloid: β, -0.33; 95% CI, -0.46 to -0.19; P < .001; married, high β-amyloid: β, -0.12; 95% CI, -0.18 to -0.01; P < .001).Conclusions and relevanceIn a sample of cognitively unimpaired older adults, being widowed was associated with accelerated β-amyloid-related cognitive decline during 3 years. Cognitively unimpaired, widowed older adults were particularly susceptible to Alzheimer disease clinical progression, emphasizing the need for increased research attention and evidenced-based interventions for this high-risk group.

Dataset Information

Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults.

Publications

Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults.

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