Authors: Dubé, Joseph B. | Johansen, Christopher T. | Robinson, John F. | Lindsay, Joan | Hachinski, Vladimir | Hegele, Robert A.
Article Type: Research Article
Abstract: Dementia is a heritable condition with devastating effects on both patients and their caregivers. Studies have identified genetic variants associated with increased susceptibility to late-onset Alzheimer disease (AD)-related dementia; however, no studies have assessed whether genetic variation is associated with the early stages of cognitive decline. Given that cerebrovascular disease is an established mechanism in which chronic ischemia increases susceptibility to dementia, we assessed whether genetic variation associated with either cardio-metabolic or AD-related traits is associated with an early stage of cognitive decline called “cognitive impairment, no dementia” (CIND). We studied 484 CIND patients and 459 cognitively healthy controls selected …from the Canadian Study of Health and Aging. We tested for association between ~200,000 genetic variants selected from genes associated with cardio-metabolic traits and CIND status using the Cardio-MetaboChip. We also assessed whether AD-related variants and APOE alleles were associated with CIND status, either individually or as part of a composite genetic risk score. We identified a potential association between the ZNF608/GRAMD3 locus, specifically the rs1439568 polymorphism and CIND status (major allele odds ratio [OR] = 1.51; p = 8.4 × 10−6 ). AD-related variants were not associated with CIND status, however APOE E4 allele frequency was significantly higher in CIND patients versus healthy controls (OR = 1.35; p = 0.044). We identified a potential association between the ZNF608/GRAMD3 locus and CIND status, although AD-related variants were not associated with CIND. Additional replication of this association signal is invited. Show more
Keywords: Alzheimer's disease, APOE, cardiovascular diseases, genome-wide association study, mild cognitive impairment, vascular dementia
DOI: 10.3233/JAD-2012-121477
Citation: Journal of Alzheimer's Disease, vol. 33, no. 3, pp. 831-840, 2013
Authors: Laurin, Danielle | Verreault, René | Lindsay, Joan | Dewailly, Éric | Holub, Bruce J.
Article Type: Research Article
Abstract: It has been suggested that the dietary intake of omega-3 polyunsaturated fatty acids could be inversely related to the risk of dementia and cognitive decline. This analysis examined the association between plasma concentration of omega-3 polyunsaturated fatty acids and prevalence and incidence of cognitive impairment and dementia. Data are reported on subjects 65 years or older who had a complete clinical evaluation at the first two waves (1991–1992 and 1996–1997) of the Canadian Study of Health and Aging. Main outcome measures were cognitive impairment and dementia by mean relative plasma concentrations of fatty acids in the phospholipid fraction at baseline. …Results were adjusted for age, sex, education, smoking, alcohol intake, body mass index, history of cardiovascular disease, and apolipoprotein E e4 genotype. In the cross-sectional analysis, no significant difference in omega-3 polyunsaturated fatty acid concentrations was observed between controls and both prevalent cases of cognitive impairment and dementia. In the prospective analysis, a higher eicosapentaenoic acid (p < 0.01) concentration was found in cognitively impaired cases compared to controls while higher docosahexaenoic acid (p < 0.07), omega-3 (p < 0.04) and total polyunsaturated fatty acid (p < 0.03) concentrations were found in dementia cases. These findings do not support the hypothesis that omega-3 polyunsaturated fatty acids play a protective role in cognitive function and dementia. Show more
Keywords: dementia, omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid
DOI: 10.3233/JAD-2003-5407
Citation: Journal of Alzheimer's Disease, vol. 5, no. 4, pp. 315-322, 2003
