Alzheimer's disease genetic risk and cognitive reserve in relationship to long-term cognitive trajectories among cognitively normal individuals.
APOE genotype
Alzheimer’s disease
Cognition
Cognitive decline
Cognitive reserve
Genetics
Polygenic risk score
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
28 03 2023
28 03 2023
Historique:
received:
12
10
2022
accepted:
12
03
2023
medline:
30
3
2023
entrez:
28
3
2023
pubmed:
29
3
2023
Statut:
epublish
Résumé
Both Alzheimer's disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition. Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by (i) apolipoprotein-E (APOE) genetic status (APOE-ε2 and APOE-ε4 vs. APOE-ε3; N = 1819) and (ii) AD polygenic risk scores (AD-PRS; N = 1175). A CR index was calculated by combining years of education and literacy scores. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, episodic memory, and executive function. In mixed-effects models, higher CR index scores were associated with better baseline cognitive performance for all cognitive outcomes. APOE-ε4 genotype and AD-PRS that included the APOE region (AD-PRS These results suggest that APOE-ε4 and non-APOE-ε4 AD polygenic risk are independently associated with global cognitive and executive function declines among individuals with normal cognition at baseline, but only APOE-ε4 is associated with declines in episodic memory. Importantly, higher levels of CR may mitigate APOE-ε4-related declines in some cognitive domains. Future research is needed to address study limitations, including generalizability due to cohort demographic characteristics.
Sections du résumé
BACKGROUND
Both Alzheimer's disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition.
METHODS
Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by (i) apolipoprotein-E (APOE) genetic status (APOE-ε2 and APOE-ε4 vs. APOE-ε3; N = 1819) and (ii) AD polygenic risk scores (AD-PRS; N = 1175). A CR index was calculated by combining years of education and literacy scores. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, episodic memory, and executive function.
RESULTS
In mixed-effects models, higher CR index scores were associated with better baseline cognitive performance for all cognitive outcomes. APOE-ε4 genotype and AD-PRS that included the APOE region (AD-PRS
CONCLUSIONS
These results suggest that APOE-ε4 and non-APOE-ε4 AD polygenic risk are independently associated with global cognitive and executive function declines among individuals with normal cognition at baseline, but only APOE-ε4 is associated with declines in episodic memory. Importantly, higher levels of CR may mitigate APOE-ε4-related declines in some cognitive domains. Future research is needed to address study limitations, including generalizability due to cohort demographic characteristics.
Identifiants
pubmed: 36978190
doi: 10.1186/s13195-023-01206-9
pii: 10.1186/s13195-023-01206-9
pmc: PMC10045505
doi:
Substances chimiques
Apolipoprotein E2
0
Apolipoproteins E
0
Apolipoprotein E4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
66Subventions
Organisme : NIA NIH HHS
ID : P30 AG066444
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG003991
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG026276
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030153
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG033655
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG070953
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059869
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058501
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG044546
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG058922
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG053303
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG027161
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG032438
Pays : United States
Organisme : NIH HHS
ID : RF1-AG059869
Pays : United States
Informations de copyright
© 2023. The Author(s).
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