Cognitive Reserve in Midlife is not Associated with Amyloid-β Deposition in Late-Life

Rawlings, Andreea M.; Sharrett, A. Richey; Mosley, Thomas H.; Wong, Dean F.; Knopman, David S.; Gottesman, Rebecca F.

doi:10.3233/jad-180785

“…This is in line with another recent study using educational attainment PGS to predict rate of cognitive decline in non-demented individuals [38]. Another recent study agreeing with our ndings showed that education and cognitive function in midlife did not affect long-term brain Aβ accumulation [39].…”

Section: Discussionsupporting

confidence: 94%

Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer's disease

Kumar

¹

,

Shoai

²

,

Palmqvist

³

et al. 2021

Preprint

0

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Background: Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability.Methods: In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence and educational attainment) to predict longitudinal cognitive change (measured by MMSE) over a mean of 4.2 years. We included 260 b-amyloid (Ab) negative cognitively unimpaired (CU) individuals, 121 Ab-positive CU (preclinical AD), 50 Ab-negative mild cognitive impairment (MCI) patients, and 127 Ab-positive MCI patients (prodromal AD). Results: The polygenic score (PGS) for intelligence (p = 2.9e-02, beta = 0.1) was protective in CU and MCI participants regardless of Ab status, while polygenic risk score for AD (p = 8.2e-03, beta = -0.12) was correlated with rate of cognitive impairment and was partially mediated by Ab-pathology (mediation effect 20 %). There was no influence of education PGS, implying that educational achievement and rate of cognitive impairment are unrelated.Conclusions: Genetic variants associated with intelligence mitigate cognitive decline independent of Ab-pathology, but the effects of genetic variants associated with AD are partly mediated by Ab-pathology.

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“…This is in line with another recent study using educational attainment PGS to predict rate of cognitive decline in non-demented individuals [38]. Another recent study agreeing with our ndings showed that education and cognitive function in midlife did not affect long-term brain Aβ accumulation [39].…”

Section: Discussionsupporting

confidence: 94%

Genetic Effects on Longitudinal Cognitive Decline During the Early Stages of Alzheimer's Disease

Kumar

¹

,

Shoai

²

,

Palmqvist

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Background Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. Methods In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence and educational attainment), and genetic variants (in a genome-wide association study [GWAS]) to predict longitudinal cognitive change (measured by MMSE) over a mean of 4.2 years. We included 555 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 206 Aβ-positive CU (preclinical AD), 110 Aβ-negative mild cognitive impairment (MCI) patients, and 146 Aβ-positive MCI patients (prodromal AD). Results Polygenic scores for AD (in Aβ-positive individuals) and intelligence (independent of Aβ-status) were associated with cognitive decline. Eight genes were associated with cognitive decline in GWAS (3 independent of Aβ-status). Conclusions AD risk genes may influence cognitive decline in early AD, while genes related to intelligence may modulate cognitive decline irrespective of disease. Therapies targeting the implicated biological pathways may modulate the clinical course of AD.

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“…This is in line with another recent study using educational attainment PGS to predict rate of cognitive decline in non-demented individuals [35]. Another recent study agreeing with our ndings showed that education and cognitive function in midlife did not affect long-term brain Aβ accumulation [36].…”

Section: Discussionsupporting

confidence: 94%

Genetic Effects on Longitudinal Cognitive Decline During the Early Stages of Alzheimer's Disease

Kumar

¹

,

Shoai

²

,

Palmqvist

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Background Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. Methods In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence and educational attainment), and genetic variants (in a genome-wide association study [GWAS]) to predict longitudinal cognitive change (measured by MMSE) over a mean of 4.2 years. We included 555 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 206 Aβ-positive CU (preclinical AD), 110 Aβ-negative mild cognitive impairment (MCI) patients, and 146 Aβ-positive MCI patients (prodromal AD). Results Polygenic scores for AD (in Aβ-positive individuals) and intelligence (independent of Aβ-status) were associated with cognitive decline. Eight genes were associated with cognitive decline in GWAS (3 independent of Aβ-status). Conclusions AD risk genes may influence cognitive decline in early AD, while genes related to intelligence may modulate cognitive decline irrespective of disease. Therapies targeting the implicated biological pathways may modulate the clinical course of AD.

show abstract

Cognitive Reserve in Midlife is not Associated with Amyloid-β Deposition in Late-Life

Cited by 13 publications

References 13 publications

Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer's disease

Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer's disease

Genetic Effects on Longitudinal Cognitive Decline During the Early Stages of Alzheimer's Disease

Genetic Effects on Longitudinal Cognitive Decline During the Early Stages of Alzheimer's Disease

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