@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 {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} } @article {9287, title = {Investigation of the independent role of a rare APOE variant (L28P; APOE*4Pittsburgh) in late-onset Alzheimer disease.}, journal = {Neurobiol Aging}, volume = {122}, year = {2023}, month = {2023 Feb}, pages = {107-111}, abstract = {

A rare missense APOE variant (L28P; APOE*4Pittsburgh), which is present only in populations with European ancestry, has been reported to be a risk factor for late-onset Alzheimer{\textquoteright}s disease (LOAD). However, due to the complete linkage disequilibrium of L28P with APOE*4 (C112R), its independent genetic association is uncertain. The original association study implicating L28P with LOAD risk was carried out in a relatively small sample size. In the current study, we have re-evaluated this association in a large case-control sample of 15,762 White U.S. subjects and investigated its independent effect in APOE 3/4 subjects, as L28P has been observed only in the heterozygous state of APOE*4 carriers and 3/4 is the most common genotype containing the APOE*4 allele. The heterozygous carrier frequency of L28P, all with APOE*4, was about 3-fold higher in AD cases than in cognitively intact controls (0.845\% vs. 0.277\%). The age- and sex-adjusted meta-analysis odds ratio (OR) was 2.87 (95\% CI: 1.34 - 6.13;~=~0.0066). Among APOE 3/4 subjects, age- and sex-adjusted meta-analysis OR was 1.53 (95\% CI: 0.70 - 3.36; p~=~0.28), indicating its effect was independent of APOE*4. The lack of statistical significance appears mainly due to the low power of 4138 subjects with the 3/4 genotype (12\% power at α= 0.05) compared to the required sample of 139,088 subjects with the 3/4 genotype to detect an OR of 1.5 at α= 0.05 and 80\% power. Our data suggesting that L28P has an independent genetic effect on AD risk is reinforced by earlier experimental findings showing that this mutation leads to significant structural and conformational changes in the ApoE4 molecule and can induce functional defects associated with neuronal Aβ42 accumulation and oxidative stress. Additional functional studies in cell-based systems and animal models will help to delineate its functional significance in the etiology of AD.

}, keywords = {Alleles, Alzheimer Disease, Animals, Apolipoprotein E3, Apolipoprotein E4, Apolipoproteins E, Genotype, Heterozygote}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2022.11.007}, author = {Fan, KangHsien and Francis, Lily and Aslam, M Muaaz and Bedison, Margret A and Lawrence, Elizabeth and Acharya, Vibha and Snitz, Beth E and Ganguli, Mary and DeKosky, Steven T and Lopez, Oscar L and Feingold, Eleanor and Kamboh, M Ilyas} }