Serum lipoprotein levels, statin use, and cognitive function in older women

BACKGROUND: Few strategies are available for the prevention of cognitive impairment in elderly persons. Serum lipoprotein levels may be important predictors of cognitive function, and drugs that lower cholesterol may be effective for the prevention of cognitive impairment. OBJECTIVE: To determine whether serum lipoprotein levels, the 4-year change in serum lipoprotein levels, and the use of statin drugs are associated with cognition in older women without dementia. DESIGN, SETTING, AND PARTICIPANTS: An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study (participants at 10 of 20 centers). MAIN OUTCOME MEASURE: The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up. Women whose score was less than 84 points (>1.5 SDs below the mean) were classified as having cognitive impairment. Lipoprotein levels (total, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol and triglycerides) were measured at baseline and at the end of the study; statin use was documented at each visit. RESULTS: Compared with women in the lower quartiles, women in the highest LDL cholesterol quartile at cognitive testing had worse mean plus minus SD Modified Mini-Mental State Examination scores (93.7 plus minus 6.0 vs 91.9 plus minus 7.6; P =.002) and an increased likelihood of cognitive impairment (adjusted odds ratio, 1.76; 95% confidence interval, 1.04-2.97). A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment (adjusted odds ratio, 0.61; 95% confidence interval, 0.36-1.03) compared with women whose levels increased. Higher total and LDL cholesterol levels, corrected for lipoprotein(a) levels, were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment, whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition. Compared with nonusers, statin users had higher mean plus minus SD Modified Mini-Mental State Examination scores (92.7 plus minus 7.1 vs 93.7 plus minus 6.1; P =.02) and a trend for a lower likelihood of cognitive impairment (odds ratio, 0.67; 95% confidence interval, 0.42-1.05), findings that seemed to be independent of lipid levels. CONCLUSIONS: High LDL and total cholesterol levels are associated with cognitive impairment, and lowering these lipoprotein levels may be a strategy for preventing impairment. The association between statin use and better cognitive function in women without dementia requires further study.     

Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study

BACKGROUND: The association between depressive disorders and subsequent cognitive decline is controversial. We tested the hypothesis that elderly women (aged 65 years and older) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms. METHODS: As part of an ongoing prospective study, we evaluated 5781 elderly, mostly white, community-dwelling women. Women completed the Geriatric Depression Scale short form. Three cognitive tests--Trails B, Digit Symbol, and a modified Mini-Mental State Examination--were administered at baseline and approximately 4 years later. Baseline, follow-up, and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis; the odds of cognitive deterioration (> or =3-point decline on the modified Mini-Mental State Examination) were determined by logistic regression. RESULTS: At baseline, 211 (3.6%) of the women had 6 or more depressive symptoms. Only 16 (7.6%) of these women were receiving antidepressant medication. Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function (P<.001 for all comparisons). For example, the baseline Digit Symbol score (mean +/- SD) was 45.5 +/- 10.7 among women with 0 to 2 symptoms of depression, 40.3 +/- 10.7 for women with 3 to 5 symptoms, and 39.0 +/- 11.3 for women with 6 or more symptoms. After adjusting for the baseline score, cognitive change scores were also inversely associated with the number of depressive symptoms (P<.001 for all comparisons). Odds ratios for cognitive deterioration using 0 to 2 symptoms as the reference were 1.6 (95% confidence interval, 1.3-2.1) for 3 to 5 symptoms and 2.3 (95% confidence interval, 1.6-3.3) for 6 or more symptoms. Results were similar after being adjusted for education, age, health status, exercise, alcohol use, functional status, and clinic site. CONCLUSIONS: Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline. Mechanisms underlying the association between these 2 common conditions need further exploration.     

Telomere length predicts poststroke mortality, dementia, and cognitive decline

OBJECTIVE: Long-term cognitive development is variable among stroke survivors, with a high proportion developing dementia. Early identification of those at risk is highly desirable to target interventions for secondary prevention. Telomere length in peripheral blood mononuclear cells was tested as prognostic risk marker. METHODS: A cohort of 195 nondemented stroke survivors was followed prospectively from 3 months after stroke for 2 years for cognitive assessment and diagnosis of dementia and for 5 years for survival. Telomere lengths in peripheral blood mononuclear cells were measured at 3 months after stroke by in-gel hybridization. Hazard ratios for survival in relation to telomere length and odds ratios for dementia were estimated using multivariate techniques, and changes in Mini-Mental State Examination scores between baseline and 2 years were related to telomere length using multivariate linear regression. RESULTS: Longer telomeres at baseline were associated with reduced risk for death (hazard ratio for linear trend per 1,000 bp = 0.52; 95% confidence interval, 0.28-0.98; p = 0.04, adjusted for age) and dementia (odds ratio for linear trend per 1,000 bp = 0.19; 95% confidence interval, 0.07-0.54; p = 0.002) and less reduction in Mini-Mental State Examination score (p = 0.04, adjusted for baseline score). INTERPRETATION: Telomere length is a prognostic marker for poststroke cognitive decline, dementia, and death.     

Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2

OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study. DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type. SETTING: Multicenter population study. PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort. MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease. RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores. CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.     

The effect of apolipoprotein E epsilon4 in the relationships of smoking and drinking to cognitive function

OBJECTIVES: To investigate the joint effect of the apolipoprotein E epsilon4 (APOE epsilon4), smoking and drinking on cognitive performance in a population-based longitudinal study of elderly men. DESIGN AND SETTING: The NHLBI Twin Study, a longitudinal cardiovascular study of World War II, white, male veterans. PARTICIPANTS: A total of 589 male participants in the third cardiovascular examination of this panel and aged 59-69 when assessed for cognitive function. OUTCOME MEASURES: Cognitive function assessed by the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Benton Visual Retention Test, APOE epsilon4 allele frequency and cardiovascular disease (CVD) health status. RESULTS: For the sample as a whole, after adjustment for age, education and CVD, smoking was significantly associated with poor cognitive function (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.2-3.2, in current smokers compared with never smokers), whereas light drinking (one or fewer drinks per day) showed a protective effect (OR = 0.6, 95% CI 0.4-0.9 compared with abstainers). Stratification by APOE epsilon4 indicated that the protective effect of light drinking was stronger and the harmful effect of smoking was weaker among APOE epsilon4 carriers than among noncarriers. CONCLUSIONS: These data suggest a possible mediating effect of the APOE epsilon4 allele in the relation of smoking and drinking to cognitive function in the elderly.     

The rate of cognitive decline in Parkinson disease

OBJECTIVES: To measure the rate and predictors of change on the Mini-Mental State Examination in patients with Parkinson disease (PD) and to compare that change with the Mini-Mental State Examination changes of patients with Alzheimer disease and nondemented subjects. PATIENTS: Patients with PD were drawn from a community-based cohort in Rogaland County, Norway. Those who were without cognitive impairment at disease onset and participated in 1 or more assessments after visit 1 were included and examined after 4 years (visit 2) and 8 years (visit 3). Motor, cognitive, and psychiatric symptoms were rated using standardized scales at visit 1. Two population-based cohorts of patients with Alzheimer disease and nondemented control subjects were included for comparison. Data were analyzed using a mixed-effects model. RESULTS: One hundred twenty-nine PD patients (57% women) were included. The mean (SD) Mini-Mental State Examination score at visit 1 was 27.3 (5.7). The mean annual decline in score from visit 1 to visit 3 was 1.1 (95% confidence interval, 0.8 to 1.3; 3.9% change from visit 1). Patients with PD and dementia (n = 49) had an annual decline from visit 1 to visit 2 of 2.3 (95% confidence interval, 2.1 to 2.5; 9.1% change from visit 1), compared with 2.6 (95% confidence interval, 2.3 to 2.8; 10.6% change from visit 1) in the patients with Alzheimer disease (n = 34) (mean annual decline among patients with PD and dementia vs patients with Alzheimer disease, not significant). The change in score for nondemented PD patients (n = 80) was small and similar to that for nondemented control subjects (n = 1621). Old age, hallucinations, and more severe motor symptoms (rigidity and motor scores mediated by nondopaminergic lesions) at visit 1 were significantly associated with a more rapid cognitive decline in patients with PD. CONCLUSIONS: The mean annual decline on the Mini-Mental State Examination for PD patients was 1 point. However, a marked variation was found. In patients with PD and dementia, the mean annual decline was 2.3, which was similar to the decline observed in patients with Alzheimer disease.     

Heritability of cognitive performance in aging twins. The National Heart, Lung, and Blood Institute Twin Study

The genetic contribution to performance on scales designed to measure mild to moderate decrements in cognitive functioning in a population at risk is unknown. In the present analysis, 134 monozygotic and 133 dizygotic male twin pairs (mean age, 63 years) were given three cognitive tests: the Mini-Mental State examination, the Iowa Screening Battery for Mental Decline, and, for comparison, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale. The primary objective of the analysis was to test for a significant heritable component to performance on these measures. A secondary objective was to determine the extent to which shared variance with significant confounders such as education, age, and depression affects the outcome of the heritability analysis. Results indicate that performance on tests intended to measure cognitive decline in the elderly does have a significant genetic component and that these estimates tend to increase after adjustment for covariates. Heritability estimates adjusted for covariates were 30% for the Iowa Screening score, 60% for the Mini-Mental State score, and 67% for the Digit Symbol Substitution score.     

Normative Data on Neuropsychological Tests for Very Old Adults Living in Retirement Villages and Hostels

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels are under-represented in the literature. This study reports normative data on the Mini-Mental State Examination, Digit Span Forwards, Digit Span Backwards, the Digit Symbol Substitution Test, the Controlled Oral Word Association Test, the Stroop Neuropsychological Screening Test and the National Adult Reading Test. Age and education showed moderate correlations with neuropsychological test performance. For all tests except the Stroop, differences between residents of retirement villages and hostels were explained by age and education. Men performed better on the NART than women, but this difference was eliminated when education was controlled for statistically.     

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels are under-represented in the literature. This study reports normative data on the Mini-Mental State Examination, Digit Span Forwards, Digit Span Backwards, the Digit Symbol Substitution Test, the Controlled Oral Word Association Test, the Stroop Neuropsychological Screening Test and the National Adult Reading Test. Age and education showed moderate correlations with neuropsychological test performance. For all tests except the Stroop, differences between residents of retirement villages and hostels were explained by age and education. Men performed better on the NART than women, but this difference was eliminated when education was controlled for statistically.     

Social vulnerability predicts cognitive decline in a prospective cohort of older Canadians

BackgroundAlthough numerous social factors have been associated with cognition in older adults, these findings have been limited by the consideration of individual factors in isolation. We investigated whether social vulnerability, defined as an index comprising many social factors, is associated with cognitive decline.MethodsIn this secondary analysis of the Canadian Study of Health and Aging, 2468 community-dwellers aged 70 and older were followed up for 5 years. The social vulnerability index incorporated 40 social variables. Each response was scored as 0 if the “deficit” was absent and 1 if it was present; the 40 deficit scores were then summed. For some analyses, index scores were split into tertiles of high, intermediate, and low social vulnerability. Cognitive decline was defined as a ≥5-point decline in the Modified Mini-Mental State Examination (3MS). Associations of social vulnerability with 5-year cognitive decline (adjusting for age, sex, frailty, and baseline cognition) were analyzed by using logistic regression.ResultsMean social vulnerability was 0.25 (standard deviation, 0.09) or 9.9 deficits of the list of 40. The median cognitive change of –1.0 (interquartile range, –6 to 2) points on the 3MS was noted at 5 years. About 743 individuals (30% of the sample) experienced a decline of ≥5 points on the 3MS. Each additional social deficit was associated with increased odds of cognitive decline (odds ratio, 1.03; 95% confidence interval, 1.00 to 1.06; P = .02). Compared with those with low social vulnerability, individuals with high social vulnerability had a 36% increased odds of experiencing cognitive decline (odds ratio, 1.36; 95% confidence interval, 1.06 to 1.74; P = .015).ConclusionsIncreasing social vulnerability, defined by using a social vulnerability index incorporating many social factors, was associated with increased odds of cognitive decline during a period of 5 years in this study of older Canadians. Further study of social vulnerability in relation to cognition is warranted, with particular attention to potential interventions to alleviate its burden.     

Disruptive behavior as a predictor in Alzheimer disease

BACKGROUND: Disruptive behavior is common in Alzheimer disease (AD). There are conflicting reports regarding its ability to predict cognitive decline, functional decline, institutionalization, and mortality. OBJECTIVE: To examine whether the presence of disruptive behavior has predictive value for important outcomes in AD. DESIGN: Using the Columbia University Scale for Psychopathology in Alzheimer Disease (administered every 6 months, for a total of 3438 visit-assessments and an average of 6.9 per patient), the presence of disruptive behavior (wandering, verbal outbursts, physical threats/violence, agitation/restlessness, and sundowning) was extracted and examined as a time-dependent predictor in Cox models. The models controlled for the recruitment cohort, recruitment center, informant status, sex, age, education, a comorbidity index, baseline cognitive and functional performance, and neuroleptic use. SETTING: Five university-based AD centers in the United States and Europe (Predictors Study). PARTICIPANTS: Four hundred ninety-seven patients with early-stage AD (mean Folstein Mini-Mental State Examination score, 20 of 30 at entry) who were recruited and who underwent semiannual follow-up for as long as 14 (mean, 4.4) years. MAIN OUTCOME MEASURES: Cognitive (Columbia Mini-Mental State Examination score, < or = 20 of 57 [approximate Folstein Mini-Mental State Examination score, < or = 10 of 30]) and functional (Blessed Dementia Rating Scale score, parts I and II, > or = 10) ratings, institutionalization equivalent index, and death. RESULTS: At least 1 disruptive behavioral symptom was noted in 48% of patients at baseline and in 83% at any evaluation. Their presence was associated with increased risks of cognitive decline (hazard ratio 1.45 [95% confidence interval (CI), 1.03-2.03]), functional decline (1.66 [95% CI, 1.17-2.36]), and institutionalization (1.47 [95% CI, 1.10-1.97]). Sundowning was associated with faster cognitive decline, wandering with faster functional decline and institutionalization, and agitation/restlessness with faster cognitive and functional decline. There was no association between disruptive behavior and mortality (hazard ratio, 0.94 [95% CI, 0.71-1.25]). CONCLUSION: Disruptive behavior is very common in AD and predicts cognitive decline, functional decline, and institutionalization but not mortality.     

Homocysteine,white matter hyperintensities,and cognition in healthy elderly people

Hyperhomocysteinemia is associated with an increased risk of vascular disease, and recent results suggest that it also could increase the risk of dementia. We examined the relationship between homocysteine and cognitive decline in 1,241 subjects aged 61 to 73 years, followed up over 4 years. Plasma homocysteine levels were determined in all participants as well as cardiovascular risk factors, apolipoprotein E genotype, plasma levels of folate, and vitamin B12. Cognitive performances were assessed repeatedly by using Mini-Mental State Examination, Trail Making Test, Digit Symbol Substitution Test, and Finger Tapping Test. At 2-year follow-up, 841 subjects underwent cerebral magnetic resonance imaging, and white matter hyperintensities were rated visually. Analyses were adjusted for all cardiovascular risk factors. Cross-sectional analyses showed that higher concentrations of homocysteine were significantly related to poorer performances at all neuropsychological tests. Longitudinal analyses confirmed this finding. The odds of cognitive decline was 2.8-fold (p < 0.05) higher in subjects with homocysteine levels above 15 micromol/L compared with those with homocysteine levels below 10 micromol/L. In participants who underwent magnetic resonance imaging, the relationship between homocysteine and cognition was unchanged after taking into account white matter hyperintensities suggesting that white matter hyperintensities do not mediate the association between homocysteine and cognition.     

Serum albumin levels predict cognitive impairment in elderly hip fracture patients

The aim of this study was to investigate the possible interrelation of serum albumin levels and cognitive function of elderly hip fracture patients. The study involved 331 elderly patients with hip fractures, admitted for rehabilitation. Cognition was assessed by Mini-Mental State Examination (MMSE). MMSE scores less than 24 points were considered suggestive of cognitive impairment. Age, serum albumin levels, and previous stroke emerged as the only statistically significant parameters differing between those with MMSE score less than 24 or higher. After adjusting for confounding variables, the middle and lowest tertiles of serum albumin levels were associated with an increased risk of cognitive impairment (odds ratio 1.97, 95% confidence interval 1.15-3.38, P < .01 vs 3.06 and 1.79-5.23, P < .001, respectively). This study shows that lower serum albumin levels are independently associated with lower MMSE scores in hip fractured elderly patients, supporting the possible role of chronic low-grade inflammation in age-related cognitive decline.     

Brain imaging evidence of preclinical Alzheimer's disease in normal aging

OBJECTIVE: This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people. METHODS: We performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community-dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini-Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores. RESULTS: Six subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid-temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini-Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini-Mental State Examination decline. INTERPRETATION: These results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology.     

Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia

OBJECTIVES To determine if prevalent and incident diabetes mellitus (DM) increase risk of cognitive decline and if, among elderly adults with DM, poor glucose control is related to worse cognitive performance. DESIGN Prospective cohort study. SETTING Health, Aging, and Body Composition Study at 2 community clinics. PARTICIPANTS A total of 3069 elderly adults (mean age, 74.2 years; 42% black; 52% female). MAIN OUTCOME MEASURES Participants completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years. Diabetes mellitus status was determined at baseline and during follow-up visits. Glycosylated hemoglobin A1c level was measured at years 1 (baseline), 4, 6, and 10 from fasting whole blood. RESULTS At baseline, 717 participants (23.4%) had prevalent DM and 2352 (76.6%) were without DM, 159 of whom developed incident DM during follow-up. Participants with prevalent DM had lower baseline test scores than participants without DM (3MS: 88.8 vs 90.9; DSST: 32.5 vs 36.3, respectively; t?=?6.09; P?=?.001 for both tests). Results from mixed-effects models showed a similar pattern for 9-year decline (3MS: -6.0- vs -4.5-point decline; t?=?2.66; P?=?.008; DSST: -7.9- vs -5.7-point decline; t?=?3.69; P?=?.001, respectively). Participants with incident DM tended to have baseline and 9-year decline scores between the other 2 groups but were not statistically different from the group without DM. Multivariate adjustment for demographics and medical comorbidities produced similar results. Among participants with prevalent DM, glycosylated hemoglobin A1c level was associated with lower average mean cognitive scores (3MS: F?=?8.2; P for overall?=?.003; DSST: F?=?3.4; P for overall?=?.04), even after multivariate adjustment. CONCLUSION Among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging.     

Exercise level and cognitive decline: the MoVIES project

Growing evidence suggests that physical exercise may be protective against cognitive impairment and decline. A prospective study of a representative rural community sample (N = 1,146) aged 65+ years examined self-reported exercise habits and measured global cognitive function using the Mini-Mental State Examination (MMSE). A composite variable "exercise level" combining type, frequency, and duration of exercise was created with three levels: "high exercise" (aerobic exercise of > or = 30 minute duration > or = 3 times a week), "low exercise" (all other exercise groups), and "no exercise." Cognitive decline was defined as being in the 90 percentile of decline in this cohort, ie, declining by 3 or more MMSE points during the 2-year interval between two assessments. In a multiple regression model, high exercise level at the baseline assessment was negatively associated with, ie, was protective against, being in the group with the greatest amount of decline at the follow-up assessment, after adjusting for likely confounders (odds ratio = 0.39; 95% confidence interval, 0.19, 0.78). When high exercise was redefined using frequency as > or = 5 days per week as the threshold, as per the Surgeon General's guidelines, both low exercise and high exercise were negatively associated with cognitive decline. Exercise may have implications for prevention of cognitive decline.     

Association between high-density lipoprotein and cognitive impairment in the oldest old

Low high-density lipoprotein cholesterol is associated with an increased risk for cardiovascular disease and stroke. At the same time, cardiovascular disease and stroke are important risk factors for dementia. We assessed the association between total and fractionated cholesterol and cognitive impairment and explored whether observed associations were dependent on or independent of atherosclerotic disease. In a population-based study, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured in 561 subjects 85 years old and grouped in three equal strata representing decreasing serum concentrations. History of cardiovascular disease and stroke was determined. All subjects completed the Mini-Mental State Examination (MMSE), and the presence of dementia was determined. Median MMSE scores were significantly lower in subjects with low high-density lipoprotein cholesterol (25 points vs 27 points, p < 0.001). No differences in MMSE scores were found for other lipids and lipoproteins. MMSE scores in subjects with and without cardiovascular disease were 26 and 27 points (p = 0.007), respectively, and in subjects with and without stroke were 21 and 26 points (p < 0.001), respectively. The associations between low MMSE scores and low high-density lipoprotein cholesterol remained significant after subjects with cardiovascular disease or stroke were excluded. In a comparison of subjects with low high-density lipoprotein cholesterol with subjects with high high-density lipoprotein cholesterol, the odds ratio for dementia was 2.3 (95% confidence interval, 1.2-4.3), and in subjects without cardiovascular disease or stroke, it was 3.7 (95% confidence interval, 1.3-10.1). All odds ratios were unaffected by education, low-density lipoprotein cholesterol, triglycerides, and survival. Low high-density lipoprotein cholesterol is associated with cognitive impairment and dementia. At least part of the association between high-density lipoprotein cholesterol and cognitive function is independent of atherosclerotic disease.     

Blood lead levels in relation to cognitive function in older U.S. adults

Studies suggest that cumulative exposure to lead, as measured in the bone, is associated with accelerated cognitive decline at older age. It is presently unclear, however, whether current blood lead levels (BLLs) are adversely related to cognitive functioning in older adults. We evaluated BLLs in relation to cognition in the continuous National Health and Nutrition Examination Survey (NHANES). The current study was limited to adults age 60 and older. We examined two measures of cognitive functioning: self-reported functional limitation due to difficulty remembering or periods of confusion (NHANES 1999-2008; n=7277) and performance on the Digit Symbol Substitution Test (DSST; NHANES 1999-2002; n=2299). We evaluated quintiles of BLL (<1.30, 1.79-<2.30, 2.30-<3.20, and ≥3.20μg/dL) in relation to cognitive functioning using logistic (functional limitation) and linear (DSST scores) regression in SUDAAN, adjusting for age, sex, race, poverty-income ratio, education, and self-reported general health status. BLLs were not associated with self-reported confusion or memory problems in crude and adjusted analyses, with adjusted odds ratios and 95% confidence intervals (CI) of 1.0 (ref.), 0.9 (CI=0.7-1.3), 0.8 (CI=0.6-1.2), 1.0 (CI=0.7-1.3), 1.0 (CI=0.7-1.4), respectively, in increasing quintiles. Similarly, there was no clear association between performance on the DSST and BLL after accounting for all covariates. Our findings add to the inconsistent evidence regarding the association between concurrent BLLs and cognitive function in older adults. Early-life or long-term, accumulated lead exposures may be etiologically more relevant to accelerated cognitive decline at older age.     

Risk factors for dementia in the cardiovascular health cognition study

BACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999. METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD). RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes. CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.     

Hypertension, white matter change and response to cholinesterase inhibitors in Alzheimer's disease

BACKGROUND: Cholinesterase inhibitors are used to treat mild to moderate Alzheimer's disease. Their role in patients with concurrent cerebrovascular disease has been less well studied, and the influence of vascular risk factors on response to treatment is uncertain. We investigated the effect of hypertension and white matter lesions (WML) on response. METHODS: A retrospective sample of 160 consecutive out-patients who had blood pressure measured and the presence or absence of WML recorded at baseline and who completed six months treatment with a cholinesterase inhibitor was studied. Subjects scored either zero or one on the Modified Hachinski Ischaemic Scale. Subjects were assessed using the Mini-Mental State Examination (MMSE), the Digit Symbol Substitution test (DSST) and both the Instrumental Activities of Daily Living (IADL) and Social Behaviour (SB) sub-scales of the Nurses Observation Scale for Geriatric Patients (NOSGER). RESULTS: 43.9% of the total study population were classified as good responders using our criteria. Neither the presence of hypertension nor the presence of WML alone influenced outcome. However, there was a statistically significant interaction between blood pressure and WML on outcome variables on multiple analysis of variance (MANOVA) (F(4, 139) = 5.60, p < 0.0005). Subjects with both hypertension and WML deteriorate to a significantly greater extent in IADL and SB scores than any other group (p < 0.05 in each case). This effect could not be explained by age or by smoking status. CONCLUSION: Our results support the hypothesis that there is an interaction between hypertension and WML that adversely influences functional change during cholinesterase inhibitor treatment. Our results are a contrast to suggestions that subjects with vascular disease show a better response to cholinesterase inhibitors. We recommend careful exploration of factors that may influence outcome.