O1-03-06: Polygenic Risk of Alzheimer's Disease and Neurodegenerative Related Traits and Their Association With Cognitive Function: Uk Biobank and the Dementias Platform Uk

Background and purpose: Previous studies testing associations between polygenic risk for late-onset Alzheimer’s disease (LOAD-PGR) and brain magnetic resonance imaging (MRI) measures have been limited by small samples and inconsistent consideration of potential confounders. This study investigates whether higher LOAD-PGR is associated with differences in structural brain imaging and cognitive values in a relatively large sample of non-demented, generally healthy adults (UK Biobank). Method: Summary statistics were used to create PGR scores for n=32,790 participants using LDpred. Outcomes included 12 structural MRI volumes and 6 concurrent cognitive measures. Models were adjusted for age, sex, body mass index, genotyping chip, 8 principal components, lifetime smoking, apolipoprotein (APOE) e4 genotype and socioeconomic deprivation. We tested for statistical interactions between APOE e4 allele dose and LOAD-PGR vs. all outcomes. Results: In fully adjusted models, LOAD-PGR was associated with worse fluid intelligence (standardised beta [β] = -0.080 per LOAD-PGR standard deviation, p = 0.002), matrix completion (β = -0.102, p = 0.003), smaller left hippocampal total (β = -0.118, p = 0.002) and body (β = -0.069, p = 0.002) volumes, but not other hippocampal subdivisions. There were no significant APOE x LOAD-PGR score interactions for any outcomes in fully adjusted models. Discussion: This is the largest study to date investigating LOAD-PGR and non-demented structural brain MRI and cognition phenotypes. LOAD-PGR was associated with smaller hippocampal volumes and aspects of cognitive ability in healthy adults, and could supplement APOE status in risk stratification of cognitive impairment/LOAD.

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Sex and APOE Genotype Differences Related to Statin Use in The Aging Population

10.21203/rs.3.rs-70804/v1 ◽

2020 ◽

Author(s):

Arianna Dagliati ◽

Niels Peek ◽

Roberta Diaz Brinton ◽

Nophar Geifman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Metabolic Diseases ◽

Survival Rates ◽

Apoe Genotype ◽

Specific Area ◽

Ageing Population ◽

Uk Biobank ◽

Statin Use

Abstract Background. Significant evidence suggests that the cholesterol-lowering statins can effect cognitive function, and reduce the risk for Alzheimer’s disease and dementia. These potential effects may be constrained by specific combinations of an individual’s sex and Apolipoprotein E (APOE) genotype. Methods. Here we examine data from 252,327 UK BioBank participants, aged 55 or over, and compare the effects of statin use in males and females. We identified that in this population, males were older, had a higher level of education, better cognitive scores, higher incidence of cardiovascular and metabolic diseases, and a higher rate of statin use.Results. We observed that males and those participants with an APOE4 (E4 variant of APOE) positive genotype had higher probabilities of being treated with statins; while participants with an Alzheimer’s diagnosis had slightly lower probabilities. We found that use of statins was not significantly associated with overall higher rates of survival. However, when considering the interaction of statin use with sex, the results suggest higher survival rates in males treated with statins. Finally, examination of cognitive function indicates a potential beneficial effect of statins, however this is limited to APOE4 positive genotypes. Conclusions. Our evaluation of the ageing population in a large cohort from the UK BioBank confirms sex and APOE genotype as funda mental risk stratifiers for Alzheimer’s disease and cognitive function, furthermore it extends them to the specific area of statin use, clarifying their specific interactions with treatments.

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Associations between Alzheimer’s disease polygenic risk scores and hippocampal subfield volumes in 17,161 UK Biobank participants

10.1101/2020.10.24.20218925 ◽

2020 ◽

Author(s):

Heidi Foo ◽

Anbupalam Thalamuthu ◽

Jiyang Jiang ◽

Forrest Koch ◽

Karen A. Mather ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Layer ◽

Community Dwelling ◽

Granule Cell Layer ◽

Risk Scores ◽

Uniform Structure ◽

Polygenic Risk Score ◽

Uk Biobank ◽

Polygenic Risk

AbstractHippocampal volume is an important biomarker of Alzheimer’s disease (AD), and genetic risk of AD is associated with hippocampal atrophy. However, the hippocampus is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRSAD) have been inadequately investigated. We examined these associations in 17,161 cognitively normal UK Biobank participants (44-80 years). Age was negatively associated with all the hippocampal subfield volumes and females had smaller volumes than men. Higher PRSAD was associated with lower volumes in the bilateral whole hippocampus, hippocampal-amygdala-transition-area (HATA), and hippocampal tail; right subiculum; left cornu ammonis (CA)1, CA4, molecular layer, and granule cell layer of dentate gyrus (CG-DG), with associations being greater on the left side. Older individuals (median age 63 years, n=8984) showed greater subfield vulnerability to high PRSAD compared to the younger group (n=8177), but the effect did not differ by sex. The pattern of subfield involvement in relation to the PRSAD in community dwelling healthy individuals sheds additional light on the pathogenesis of AD.

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The role of Alzheimer’s disease polygenic risk scores in changes of cognitive function in older adults: A longitudinal cohort study

Alzheimer s & Dementia ◽

10.1002/alz.037853 ◽

2020 ◽

Vol 16 (S3) ◽

Author(s):

Gongbu Pan ◽

Anna E. King ◽

Aidan Bindoff ◽

Mathew J. Summers ◽

James C. Vickers ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cohort Study ◽

Cognitive Function ◽

Longitudinal Cohort Study ◽

Risk Scores ◽

Longitudinal Cohort ◽

Polygenic Risk

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Association between polygenic risk for Alzheimer’s disease, brain structure and cognitive abilities in UK Biobank

Neuropsychopharmacology ◽

10.1038/s41386-021-01190-4 ◽

2021 ◽

Author(s):

Rachana Tank ◽

Joey Ward ◽

Kristin E. Flegal ◽

Daniel J. Smith ◽

Mark E. S. Bailey ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Fluid Intelligence ◽

Late Onset ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Healthy Adults ◽

Uk Biobank ◽

Polygenic Risk ◽

Structural Brain

AbstractPrevious studies testing associations between polygenic risk for late-onset Alzheimer’s disease (LOAD-PGR) and brain magnetic resonance imaging (MRI) measures have been limited by small samples and inconsistent consideration of potential confounders. This study investigates whether higher LOAD-PGR is associated with differences in structural brain imaging and cognitive values in a relatively large sample of non-demented, generally healthy adults (UK Biobank). Summary statistics were used to create PGR scores for n = 32,790 participants using LDpred. Outcomes included 12 structural MRI volumes and 6 concurrent cognitive measures. Models were adjusted for age, sex, body mass index, genotyping chip, 8 genetic principal components, lifetime smoking, apolipoprotein (APOE) e4 genotype and socioeconomic deprivation. We tested for statistical interactions between APOE e4 allele dose and LOAD-PGR vs. all outcomes. In fully adjusted models, LOAD-PGR was associated with worse fluid intelligence (standardised beta [β] = −0.080 per LOAD-PGR standard deviation, p = 0.002), matrix completion (β = −0.102, p = 0.003), smaller left hippocampal total (β = −0.118, p = 0.002) and body (β = −0.069, p = 0.002) volumes, but not other hippocampal subdivisions. There were no significant APOE x LOAD-PGR score interactions for any outcomes in fully adjusted models. This is the largest study to date investigating LOAD-PGR and non-demented structural brain MRI and cognition phenotypes. LOAD-PGR was associated with smaller hippocampal volumes and aspects of cognitive ability in healthy adults and could supplement APOE status in risk stratification of cognitive impairment/LOAD.

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