@article {801, title = {Stroke risk factors and loss of high cognitive function.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Sep 14}, pages = {793-9}, abstract = {

BACKGROUND: Modifiable stroke risk factors may contribute to age-associated declines in cognitive function. Individuals with high levels of cognitive function after midlife may have less exposure to these stroke risk factors or may be less susceptible to their effects on cognition.

METHODS: The Cardiovascular Health Study (CHS)* is a population-based, longitudinal cohort study of 5,888 people age 65 years and older. Participants (n = 4,129) who were free of dementia, stroke, or TIA at the time of baseline cranial MRI were selected for analysis. High cognitive function at baseline was defined by performance at or above midlife norms on the Modified Mini-Mental State Examination (3MS).

RESULTS: The odds of having high cognitive function at baseline decreased by quartile of stroke risk (highest vs lowest risk quartile, adjusted odds ratio [OR] 0.68; 95\% CI 0.52 to 0.88; p for trend = 0.005). Stroke risk was a predictor of decline on the 3MS in those with typical levels of cognitive function at baseline, even in the absence of incident stroke or TIA (highest vs lowest risk quartile for 3MS decline, adjusted OR 2.11; 95\% CI 1.42 to 3.13; p for trend < 0.001). In contrast, stroke risk was not associated with decline on the 3MS in those with high cognitive function at baseline (p = 0.03 for interaction).

CONCLUSIONS: In a cohort of older adults without stroke, TIA, or dementia, cognitive function and incident cognitive decline were associated with risk for stroke. Additional studies are needed to determine whether modification of stroke risk factors can reduce the cognitive decline that is often attributed to normal aging.

}, keywords = {Aged, Aged, 80 and over, Aging, Cognition Disorders, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Higher Nervous Activity, Humans, Incidence, Male, Risk Assessment, Risk Factors, Sampling Studies, Sensitivity and Specificity, Severity of Illness Index, Stroke, United States}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000137014.36689.7f}, author = {Elkins, J S and O{\textquoteright}Meara, E S and Longstreth, W T and Carlson, M C and Manolio, T A and Johnston, S C} } @article {870, title = {Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1409-14}, abstract = {

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS).

METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician{\textquoteright}s assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4.

RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28\% (95\% CI: 0.51 to 1.02), and AD by 41\% (95\% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect.

CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

}, keywords = {Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Cohort Studies, Dementia, Dietary Fats, Unsaturated, Fatty Acids, Omega-3, Feeding Behavior, Female, Fish Oils, Fish Products, Food, Formulated, Genetic Predisposition to Disease, Humans, Incidence, Male, Risk Factors, Socioeconomic Factors, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000183148.34197.2e}, author = {Huang, T L and Zandi, P P and Tucker, K L and Fitzpatrick, A L and Kuller, L H and Fried, L P and Burke, G L and Carlson, M C} } @article {851, title = {Neuropsychological characteristics of mild cognitive impairment subgroups.}, journal = {J Neurol Neurosurg Psychiatry}, volume = {77}, year = {2006}, month = {2006 Feb}, pages = {159-65}, abstract = {

OBJECTIVE: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study.

METHODS: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition.

RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5\%) had memory deficits, and 6 (21.5\%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits.

CONCLUSIONS: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16\% of all MCI cases and 21.5\% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Amnesia, Cognition Disorders, Female, Humans, Male, Neuropsychological Tests, Psychometrics, Reference Values}, issn = {0022-3050}, doi = {10.1136/jnnp.2004.045567}, author = {Lopez, O L and Becker, J T and Jagust, W J and Fitzpatrick, A and Carlson, M C and DeKosky, S T and Breitner, J and Lyketsos, C G and Jones, B and Kawas, C and Kuller, L H} } @article {1031, title = {Knee height and arm span: a reflection of early life environment and risk of dementia.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 May 06}, pages = {1818-26}, abstract = {

OBJECTIVES: To determine if anthropometric measures, as markers of early life environment, are associated with risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD).

METHODS: A total of 2,798 subjects were followed as part of the Cardiovascular Health Cognition Study for an average of 5.4 years; 480 developed dementia. Knee height was measured 3 years prior to and arm span 4 years after the study{\textquoteright}s baseline. Cox proportional hazard models were used to examine their association with subsequent risk of dementia, AD, and VaD.

RESULTS: Among women, greater knee height and arm span were associated with lower risks of dementia (knee height: HR per 1-inch increase 0.84; 95\% CI 0.74-0.96; arm span: HR per 1-inch increase 0.93; 95\% CI 0.88-0.98) and AD (knee height: HR per 1-inch increase 0.78; 95\% CI 0.65-0.93; arm span: HR per 1-inch increase 0.90; 95\% CI 0.85-0.96). Women in the lowest quartile of arm span had approximately 1.5 times greater risk of dementia (HR 1.45; 95\% CI 1.03-2.05) and AD (HR 1.70; 95\% CI 1.10-2.62) than other women. Among men, only arm span was associated with lower risks of dementia (HR per 1-inch increase 0.94; 95\% CI 0.89-1.00) and AD (HR per 1-inch increase 0.92; 95\% CI 0.84-1.00). For each gender, knee height was not associated with VaD, while arm span was associated with a nonsignificant lower risk of VaD.

CONCLUSIONS: Our findings with knee height and arm span are consistent with previous reports and suggest early life environment may play an important role in the determination of future dementia risk.

}, keywords = {Aged, Aged, 80 and over, Aging, Anthropometry, Arm, Body Height, Brain, Child, Child, Preschool, Dementia, Environment, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Knee, Male, Middle Aged, Prospective Studies, Risk Factors, Sex Characteristics, Skeleton}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000311444.20490.98}, author = {Huang, T L and Carlson, M C and Fitzpatrick, A L and Kuller, L H and Fried, L P and Zandi, P P} } @article {1335, title = {The association of genetic variants in interleukin-1 genes with cognition: findings from the cardiovascular health study.}, journal = {Exp Gerontol}, volume = {46}, year = {2011}, month = {2011 Dec}, pages = {1010-9}, abstract = {

The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer{\textquoteright}s, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47, 95\%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95\%CI=-0.13,-0.60, p=0.0027; rs931471: beta=0.39, 95\%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African Americans (rs1143627: beta=1.6, 95\%CI=0.48, 2.8; p=0.006 and rs1143634: beta=2.09, 95\%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.

}, keywords = {African Americans, Aged, Aged, 80 and over, Cognition, Cognition Disorders, Dementia, Educational Status, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Interleukin 1 Receptor Antagonist Protein, Interleukin-1alpha, Interleukin-1beta, Linkage Disequilibrium, Longitudinal Studies, Male, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, United States}, issn = {1873-6815}, doi = {10.1016/j.exger.2011.09.005}, author = {Benke, K S and Carlson, M C and Doan, B Q and Walston, J D and Xue, Q L and Reiner, A P and Fried, L P and Arking, D E and Chakravarti, A and Fallin, M D} }