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Effect of Alzheimer's disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study.
Tuesday,2012-11-06 12:26 America/Los_Angeles — eenright
| Title | Effect of Alzheimer's disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Sweet, RA, Seltman, H, Emanuel, JE, Lopez, OL, Becker, JT, Bis, JC, Weamer, EA, Demichele-Sweet, MAnn A, Kuller, LH |
| Journal | Am J Psychiatry |
| Volume | 169 |
| Issue | 9 |
| Pagination | 954-62 |
| Date Published | 2012 Sep |
| ISSN | 1535-7228 |
| Keywords | Age of Onset, Aged, Alleles, Alzheimer Disease, Apolipoprotein E4, Bayes Theorem, Clusterin, Cohort Studies, Dementia, Disease Progression, Female, Genetic Predisposition to Disease, Humans, Male, Models, Psychological, Monomeric Clathrin Assembly Proteins, Polymorphism, Single Nucleotide, Receptors, Complement 3b, Risk Factors |
| Abstract | <p><b>OBJECTIVE: </b>The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease.</p><p><b>METHOD: </b>The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end.</p><p><b>RESULTS: </b>The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors.</p><p><b>CONCLUSIONS: </b>Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease.</p> |
| DOI | 10.1176/appi.ajp.2012.11121815 |
| Alternate Journal | Am J Psychiatry |
| PubMed ID | 22952074 |
| PubMed Central ID | PMC3610571 |
| Grant List | N0-1-HC-85239 / HC / NHLBI NIH HHS / United States AG15928 / AG / NIA NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States AG05133 / AG / NIA NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States HL087251 / HL / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R01 AG027224 / AG / NIA NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States AG20098 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States AG027224 / AG / NIA NIH HHS / United States |