Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia

Introduction 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)

Atherosclerotic calcification is related to a higher risk of dementia and cognitive decline

Background: Longitudinal data on the role of atherosclerosis in different vessel beds in the etiology of cognitive impairmen

Depressive symptoms predict incident dementia during short- but not long-term follow-up period

Background: Whether depression is a long-term risk factor for dementia or represents a dementia prodrome is unclear. Therefore, we examined the relationship between depressive symptoms and dementia during short and long follow-up in a population-based cohort. Methods: In the Rotterdam Study, 4393 nondemented individuals were followed for incident dementia for 13.7 years by continuous monitoring. Cox proportional hazards models for different time intervals were used to estimate the risk of incident dementia. Results: Five-hundred eighty-two participants developed dementia during 13.7 years. Persons with depressive symptoms had an 8% increased risk of dementia compared with those without depressive symptoms during the overall follow-up. The risk was highest in the short and intermediate follow-up, particularly in men. We did not find an association in the follow-up period beyond 10 years. Conclusion: Our results suggest that late-life depressive symptoms are part of a dementia prodrome rather than an independent risk factor of dementia