@article {1227, title = {Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study.}, journal = {Am J Geriatr Psychiatry}, volume = {19}, year = {2011}, month = {2011 Feb}, pages = {160-8}, abstract = {

OBJECTIVE: To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI).

DESIGN: : The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data.

SETTING: Community.

PARTICIPANTS: The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-∊ (APOE) genotyping.

MEASUREMENTS: The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status.

RESULTS: : Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis.

CONCLUSIONS: Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process.

}, keywords = {Aged, Alzheimer Disease, Chi-Square Distribution, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Psychiatric Status Rating Scales, Psychotic Disorders, Time Factors}, issn = {1545-7214}, doi = {10.1097/JGP.0b013e3181e446c8}, author = {Emanuel, James E and Lopez, Oscar L and Houck, Patricia R and Becker, James T and Weamer, Elise A and Demichele-Sweet, Mary Ann A and Kuller, Lewis and Sweet, Robert A} } @article {1405, title = {Effect of Alzheimer{\textquoteright}s disease risk genes on trajectories of cognitive function in the Cardiovascular Health Study.}, journal = {Am J Psychiatry}, volume = {169}, year = {2012}, month = {2012 Sep}, pages = {954-62}, abstract = {

OBJECTIVE: The trajectory of cognitive decline in patients with late-onset Alzheimer{\textquoteright}s disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer{\textquoteright}s disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease.

METHOD: 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{\textquoteright}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{\textquoteright}s end.

RESULTS: The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model{\textquoteright}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.

CONCLUSIONS: Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer{\textquoteright}s disease.

}, 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}, issn = {1535-7228}, doi = {10.1176/appi.ajp.2012.11121815}, author = {Sweet, Robert A and Seltman, Howard and Emanuel, James E and Lopez, Oscar L and Becker, James T and Bis, Joshua C and Weamer, Elise A and Demichele-Sweet, Mary Ann A and Kuller, Lewis H} }