The potential roles of genetic factors in predicting ageing-related cognitive change and Alzheimer's disease.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic search or meta-analytic methodology.
PubMed 34242808 · doi:10.1016/j.arr.2021.101402
What was done
The authors reviewed published literature on genetic risk factors for Alzheimer's disease (AD) and age-related cognitive decline, focusing on known genetic loci (including APOE, BDNF, PICALM, CLU, APP, PSEN1, and PSEN2) and potential sources of unexplained heritability.
What was found
The abstract provides no quantitative data or numerical estimates. It notes that established measured loci do not account for a large portion of AD heritability, which may instead stem from rare variants, gene-gene interactions, gene-environment interactions, or epigenetic mechanisms. It also notes a paucity of longitudinal studies investigating genetic predictors of preclinical cognitive change during ageing.
Why it matters
This review highlights persistent gaps in understanding the genetic architecture of AD and identifies future priorities, particularly the need to track genetic influences on cognitive trajectories longitudinally.
Limits
The abstract describes a narrative overview rather than a systematic review or meta-analysis; no search protocols, study counts, or quantitative pooled estimates are reported. Specific effect sizes and clinical predictive performance of the cited genes are not provided in the abstract.
Cited by
- supports Neurodegenerative diseases, including Alzheimer's disease, are rarely caused by a single mutation in a single gene; the vast majority of cases are caused by a combination of many hundreds or thousands of genetic risk factors interacting with environmental and lifestyle exposures.