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Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia
Author(s) -
Adams Hieab H.H.,
Bruijn Renée F.A.G.,
Hofman Albert,
Uitterlinden André G.,
Duijn Cornelia M.,
Vernooij Meike W.,
Koudstaal Peter J.,
Ikram M. Arfan
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.12.008
Subject(s) - dementia , odds ratio , rotterdam study , amyotrophic lateral sclerosis , medicine , hazard ratio , frontotemporal lobar degeneration , frontotemporal dementia , disease , population , oncology , alzheimer's disease , psychology , confidence interval , environmental health
Neurodegenerative diseases are a major cause of cognitive impairment and can ultimately lead to dementia. Genome‐wide association studies have uncovered many genetic variants conferring risk of neurodegenerative diseases, but their role in cognitive impairment remains unexplored. Methods In the prospective, population‐based Rotterdam Study, 3605 nondemented persons aged ≥55 years were genotyped, screened for mild cognitive impairment (MCI) in 2002 to 2005 and underwent continuous follow‐up for dementia until 2012. Weighted polygenic risk scores of genetic variants for Alzheimer's disease (AD), Parkinson's disease (PD), and the frontotemporal lobar degeneration/amyotrophic lateral sclerosis disease spectrum (FTLD/ALS) were constructed and investigated for association with MCI and the subsequent conversion to dementia. Results In total, 360 (10.0%) persons had MCI, of whom 147 (4.1%) were amnestic and 213 (5.9%) nonamnestic. The AD risk score was associated with both MCI subtypes (odds ratio for all MCI 1.15 [95% CI, 1.03–1.28]), whereas PD and FTLD/ALS risk scores were associated only with nonamnestic MCI (odds ratios 1.15 [1.00–1.32] and 1.19 [1.03–1.37], respectively). The AD risk score, but not PD and FTLD/ALS risk scores, was associated with an increased risk of dementia (hazard ratio 1.55 [1.37–1.77]). Discussion Genetic evidence supports the view that multiple neurodegenerative pathways lead to MCI and that the subsequent conversion to dementia, primarily of the AD subtype, is mainly due to the AD pathway(s).