@article {947, title = {Incidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study.}, journal = {Arch Neurol}, volume = {64}, year = {2007}, month = {2007 Mar}, pages = {416-20}, abstract = {

OBJECTIVES: To examine the incidence of dementia in subjects with mild cognitive impairment (MCI) in the Cardiovascular Health Study Cognition Study.

DESIGN: Prospective epidemiological study.

SETTING: The Cardiovascular Health Study Cognition Study of Pittsburgh, Pa, was conducted from 2002 through 2003 to determine the incidence of dementia in participants classified as having MCI in 1998 and 1999. Subjects There were 136 subjects with MCI. Mild cognitive impairment was subclassified as MCI amnestic type and MCI multiple cognitive deficits type (MCI-MCDT); subjects with MCI-MCDT were also grouped based on the presence of a memory impairment. Subjects with MCI were classified as possible when there were comorbidities that could explain the subjects{\textquoteright} cognitive deficits and as probable when there were none. Main Outcome Measure Dementia.

RESULTS: The incidence of all dementias in the subjects with MCI was 147 per 1000 person-years (mean follow-up overall, 4.3 years). Of the 136 subjects with MCI, 69 (51\%) in 1998 through 1999 progressed to dementia (57 [83\%] to Alzheimer disease [AD]), but 25 (18\%) returned to normal. Of the 10 subjects with probable MCI amnestic type, 7 (70\%) progressed to dementia (all of them to AD) and none returned to normal, whereas 7 (41\%) of the 17 subjects with possible MCI amnestic type became demented (6 [86\%] to AD) and 3 (18\%) returned to normal. Of the 40 subjects with probable MCI-MCDT, 21 (52\%) progressed to dementia (17 [81\%] to AD) and 2 (5\%) returned to normal. Of the 69 subjects with possible MCI-MCDT, 34 (49\%) progressed to dementia (28 [82\%] to AD) and 20 (29\%) returned to normal. Among the subjects with probable MCI-MCDT, 15 (54\%) of 28 with and 6 (50\%) of 12 without memory deficits progressed to dementia.

CONCLUSIONS: Subjects with MCI are at high risk for dementia. The probable MCI diagnosis identified individuals in the earliest stages of dementia, usually AD, whereas the possible MCI diagnosis identified a more heterogeneous group. However, this latter group had only a slightly lower rate of conversion to dementia than the group with probable MCI, suggesting that even with comorbid conditions, there is a high likelihood of the presence of a progressive dementing disorder.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular System, Cognition Disorders, Dementia, Disease Progression, Female, Humans, Incidence, Male, Retrospective Studies}, issn = {0003-9942}, doi = {10.1001/archneur.64.3.416}, author = {Lopez, Oscar L and Kuller, Lewis H and Becker, James T and Dulberg, Corinne and Sweet, Robert A and Gach, H Michael and DeKosky, Steven T} } @article {1118, title = {Depressed mood is not a risk factor for incident dementia in a community-based cohort.}, journal = {Am J Geriatr Psychiatry}, volume = {17}, year = {2009}, month = {2009 Aug}, pages = {653-63}, abstract = {

OBJECTIVES: To determine the relationship between depressed mood and the development of Alzheimer disease in cognitively normal individuals.

DESIGN: Longitudinal and observational.

SETTING: Community-based cohort study.

PARTICIPANTS: A total of 288 participants in the Cardiovascular Health Study-Cognition Study (mean age: 77.52, SD =3.65, range: 70-89). All of the participants were adjudicated as cognitively normal in 1998/1999, and all had at least three visits before 1998/1999 with measures of cognition and mood state. The mean length of follow-up from 1998-1999 to 2007 was 7.1 years (range: 1-9 years, median =9 years).

MEASUREMENTS: The Center for Epidemiological Studies-Depression Scale (CESD) was used to index mood state, and the Modified Mini-Mental State Examination (3MSE) was the index of cognitive function among participants before 1998/1999. These measures were considered in two ways: participants were classified according to: 1) whether they showed a high-negative correlation between their CESD and 3MSE scores (i.e., indicating that greater depression was linked to poorer cognition) and 2) whether they showed persistently elevated CESD scores. The study outcome, development of dementia (N = 48), was based on consensus classifications, which was based on detailed neuropsychological and neurological exams.

RESULTS: The authors could find no consistent relationship between mood state, either alone or in relation to cognitive status, and the subsequent development of dementia. Those individuals whose cognitive functions were highly correlated with their mood state were no more likely to develop dementia than other participants. Those who had persistently depressed mood were also no more likely to develop dementia than those without persistently depressed mood.

CONCLUSION: Within the confines of this prospective, community-based study of elderly adults, the authors could not find strong evidence to support the hypothesis that mood disturbance was linked with the development of dementia.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Dementia, Depression, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Prospective Studies, Psychiatric Status Rating Scales, Residence Characteristics, Risk Factors}, issn = {1545-7214}, author = {Becker, James T and Chang, Yue-Fang and Lopez, Oscar L and Dew, Mary Amanda and Sweet, Robert A and Barnes, Deborah and Yaffe, Kristine and Young, Jeffrey and Kuller, Lewis and Reynolds, Charles F} } @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} } @article {1557, title = {Incidence of mild cognitive impairment in the Pittsburgh Cardiovascular Health Study-Cognition Study.}, journal = {Neurology}, volume = {79}, year = {2012}, month = {2012 Oct 09}, pages = {1599-606}, abstract = {

OBJECTIVES AND METHODS: The purpose of this study was to examine the incidence of mild cognitive impairment (MCI) and patterns of progression from incident MCI to dementia in 285 cognitively normal subjects (mean age, 78.9 years) in the Cardiovascular Health Study-Cognition Study from 1998-1999 to 2010-2011.

RESULTS: Two hundred (70\%) of the participants progressed to MCI; the age-adjusted incidence of MCI was 111.09 (95\% confidence interval, 88.13-142.95) per 1,000 person-years. A total of 107 (53.5\%) of the incident MCI subjects progressed to dementia. The mean time from MCI to dementia was 2.8 {\textpm} 1.8 years. Forty (20\%) of the incident MCI cases had an "unstable" course: 19 (9.5\%) converted to MCI and later returned to normal; 10 (5\%) converted to MCI, to normal, and later back to MCI; 7 (3.5\%) converted to MCI, to normal, to MCI, and later to dementia; and 4 (2\%) converted to MCI, to normal, and later to dementia. There was an increased mortality rate among the cognitively normal group (110.10 per 1,000 person-years) compared to those with incident MCI who converted to dementia (41.32 per 1,000 person-years).

CONCLUSIONS: The majority of the subjects aged >80 years developed an MCI syndrome, and half of them progressed to dementia. Once the MCI syndrome was present, the symptoms of dementia appeared within 2 to 3 years. Progression from normal to MCI or from normal to MCI to dementia is not always linear; subjects who developed MCI and later returned to normal can subsequently progress to dementia. Competing mortality and morbidity influence the study of incident MCI and dementia in population cohorts.

}, keywords = {Aged, Aged, 80 and over, Cognitive Dysfunction, Dementia, Disease Progression, Female, Health Surveys, Humans, Incidence, Male, Risk Factors, Severity of Illness Index}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31826e25f0}, author = {Lopez, Oscar L and Becker, James T and Chang, Yue-Fang and Sweet, Robert A and DeKosky, Steven T and Gach, Michael H and Carmichael, Owen T and McDade, Eric and Kuller, Lewis H} }