F. W. Unverzagt

Vascular risk factors and cognitive impairment in a stroke-free cohort

Objective: To examine vascular risk factors, as measured by the Framingham Stroke Risk Profile (FSRP), to predict incident cognitive impairment in a large, national sample of black and white adults age 45 years and older. Methods: Participants included subjects without stroke at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with at least 2 cognitive function assessments during the follow-up (n = 23,752). Incident cognitive impairment was defined as decline from a baseline score of 5 or 6 (of possible 6 points) to the most recent follow-up score of 4 or less on the Six-item Screener (SIS). Subjects with suspected stroke during follow-up were censored. Results: During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment. Baseline FSRP score was associated with incident cognitive impairment. An adjusted model revealed that male sex (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.43–1.77), black race (OR = 2.09, 95% CI 1.88–2.35), less education (less than high school graduate vs college graduate, OR = 2.21, 95% CI 1.88–2.60), older age (10-year increments, OR = 2.11, per 10-year increase in age, 95% CI 2.05–2.18), and presence of left ventricular hypertrophy (LVH, OR = 1.29, 95% CI 1.06–1.58) were related to development of cognitive impairment. When LVH was excluded from the model, elevated systolic blood pressure was related to incident cognitive impairment. Conclusions: Total FSRP score, elevated blood pressure, and LVH predict development of clinically significant cognitive dysfunction. Prevention and treatment of high blood pressure may be effective in preserving cognitive health.

Use of anticholinergics and the risk of cognitive impairment in an African American population

Background: Anticholinergic properties of certain medications often go unrecognized, and are frequently used by the elderly population. Few studies have yet defined the long-term impact of these medications on the incidence of cognitive impairment. Methods: We report a 6-year longitudinal, observational study, evaluating 1,652 community-dwelling African American subjects over the age of 70 years who were enrolled in the Indianapolis-Ibadan Dementia Project between 2001 and 2007 and who had normal cognitive function at baseline. The exposure group included those who reported the baseline use of possible or definite anticholinergics as determined by the Anticholinergic Cognitive Burden scale. Our main outcome measure was the incidence of cognitive impairment, defined as either dementia or cognitive impairment not dementia, or poor performance on a dementia screening instrument during the follow-up period. Results: At baseline, 53% of the population used a possible anticholinergic, and 11% used a definite anticholinergic. After adjusting for age, gender, educational level, and baseline cognitive performance, the number of definite anticholinergics was associated with an increased risk of cognitive impairment (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.07–1.99; p = 0.02), whereas the number of possible anticholinergics at baseline did not increase the risk (OR 0.96, 95% CI 0.85–1.09; p = 0.55). The risk of cognitive impairment among definite anticholinergic users was increased if they were not carriers of the APOE ε4 allele (OR 1.77, 95% CI 1.03–3.05; p = 0.04). Conclusions: Limiting the clinical use of definite anticholinergics may reduce the incidence of cognitive impairment among African Americans.

Association of higher diastolic blood pressure levels with cognitive impairment

Background: We evaluated the cross-sectional relationship of blood pressure (BP) components with cognitive impairment after adjusting for potential confounders. Methods: Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national, longitudinal population cohort evaluating stroke risk in 30,228 black and white men and women ≥45 years old. During the in-home visit, BP measurements were taken as the average of 2 measurements using a standard aneroid sphygmomanometer. Excluding participants with prior stroke or TIA, the present analysis included 19,836 participants (enrolled from December 2003 to March 2007) with complete baseline physical and cognitive evaluations. Incremental logistic models examined baseline relationships between BP components (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) and impaired cognitive status (score of ≤4 on 6-Item Screener) after adjusting for demographic and environmental characteristics, cardiovascular risk factors, depressive symptoms, and current use of any antihypertensive medication. Results: Higher DBP levels were associated with impaired cognitive status after adjusting for demographic and environmental characteristics, risk factors, depressive symptoms, and antihypertensive medications. An increment of 10 mm Hg in DBP was associated with a 7% (95% confidence interval [CI] 1%–14%, p = 0.0275) higher odds of cognitive impairment. No independent association was identified between impaired cognitive status and SBP (odds ratio [OR] 1.02, 95% CI 0.99–1.06) or PP (OR 0.99, 95% CI 0.95–1.04). There was no evidence of nonlinear relationships between any of the BP components and impaired cognitive status. There was no interaction between age and the relationship of impaired cognitive status with SBP (p = 0.827), DBP (p = 0.133), or PP (p = 0.827) levels. Conclusions: Higher diastolic blood pressure was cross-sectionally and independently associated with impaired cognitive status in this large, geographically dispersed, race- and sex-balanced sample of stroke-free individuals.

Cholesterol, APOE genotype, and Alzheimer disease: An epidemiologic study of Nigerian Yoruba

Objective: To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Methods: Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimers Disease and Related Disorders Association criteria. Results: Logistic regression models showed interaction after adjusting for age and gender between APOE-ε4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-ε4 allele, but not in those with APOE-ε4. There was no significant association between levels of triglycerides and AD risk in those without APOE-ε4. Conclusions: There was a significant interaction between cholesterol, APOE-ε4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Epidemiology of dementia in Nigeria: results from the Indianapolis-Ibadan study.

We determined the prevalence of dementia in a cohort of 2494 elderly Nigerians residents in Idikan Community, Ibadan, Nigeria. We utilized the Community Screening Instrument for Dementia to select subjects for clinical assessment in the second stage. The findings were compared with those of 2212 African Americans living in Indianapolis, studied simultaneously using similar methodology. The overall age‐adjusted prevalence rates of dementia and Alzheimers disease in Ibadan were 2.29% and 1.41%, respectively. These rates were much lower than the respective values of 8.24% and 6.24% obtained for African Americans. In Ibadan, Alzheimers disease accounted for 64.3% of the cases, with old age and female gender being the significant risk factors, whilst ‘living with others’ appeared to be protective (P < 0.05). Amongst African Americans, on the other hand, old age, rural living below the age of 19 years, low educational attainment and family history of dementia were the risk factors. There was a lack of association between Alzheimers disease and possession of the apolipoprotein E ε4 allele in the Nigerian sample, unlike the finding in African Americans, where significant association was shown. In addition, the frequencies of the vascular risk factors investigated were lower in Nigerians.

Association of statin use with cognitive decline in elderly African Americans

Background: Previously reported associations between statin use and incident dementia or cognitive decline have been inconsistent. We report the results from a 3-year prospective study on the association of statin use on cognitive decline and incident dementia in elderly African Americans. Methods: A community-based cohort of 1,146 African Americans aged 70 and older living in Indianapolis, Indiana, was evaluated in 2001 and 2004. The instrument used for cognitive assessment was the Community Screening Interview for Dementia (CSI-D). Cognitive decline was defined as CSI-D scores measured at 2001 minus scores at 2004. Measurements of low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) were obtained from baseline blood samples. Results: Adjusting for age at baseline, gender, education, and the possession of ApoE ε4 allele, baseline statin use was associated with less cognitive decline (p = 0.0177). There were no significant interactions of statin use when LDL-C and CRP were included. Logistic regression with the four independent variables showed that statin use may be associated with a reduction in incident dementia (OR = 0.32; p = 0.0673). Association with cognitive decline was less clear when investigating statin use over time. Significance remained only for those who discontinued prior to follow-up compared to continuous users or users who started after baseline. Conclusions: The relationship between statin use and cognitive decline is complex and subjected to unknown confounders. This effect may not be associated with the cholesterol lowering or anti-inflammatory action of statins. GLOSSARY: AD = Alzheimer disease; ANCOVA = analysis of covariance; BMI = body mass index; CAMDEX = Cambridge Examination for Mental Disorders of the Elderly informant interview; CERAD = Consortium to Establish a Registry for Alzheimer’s Disease; CHIF = Clinician Home-based Interview to assess Function; CRP = C-reactive protein; CSI-D = Community Screening Instrument for Dementia; HDL = high-density lipoprotein; HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A; LDL-C = low-density lipoprotein cholesterol; LLAs = lipid-lowering agents; NSAIDs = nonsteroidal anti-inflammatory drugs.

Cognitive decline and education in mild dementia

Recent studies suggested that education may modify the clinical expression of dementia and Alzheimers disease through its association with a brain reserve capacity. We studied whether education would be related to degree of cognitive decline in mild dementia. Equations to estimate premorbid cognitive ability were derived from a representative normative sample of 83 community-dwelling African Americans using age, education, and gender as independent variables and Word List Learning (WLL) and Animal Fluency (AF) scores from the Consortium to Establish a Registry for Alzheimers Disease(CERAD) neuropsychological test battery as dependent variables. These equations were applied to a second sample of 131 African Americans (22 with dementia, 109 healthy) who completed CERAD test batteries as part of an epidemiologic study of dementia in the community. Differences between obtained and estimated premorbid WLL and AF test scores were calculated and then analyzed in a 2 (Education) × 2 (Diagnosis) ANOVA. A significant interaction association between Education and Diagnosis on WLL scores and a borderline significant interaction on AF scores showed that the high-education demented group had a greater cognitive decline from estimated premorbid levels than the low-education demented group. Thus, at comparable levels of clinical dementia severity, greater cognitive decline occurred in highly educated patients than in low-educated patients.

International studies in dementia with particular emphasis on populations of African origin

Epidemiologic studies on dementia generally have 2 major interacting objectives: descriptive, where rates of dementia and Alzheimer Disease (AD) are calculated for communities and selected populations, and analytic, which attempt to explain the observed phenotypic variations in communities and populations by identifying disease risk factors. The public health benefits derived from descriptive studies are exemplified by the recent published review of the global prevalence of dementia under the auspices of Alzheimer Disease International. This review emphasized the enormous and growing burden associated with dementia particularly for countries in the developing world and outlined strategies to influence policy making, planning, and healthcare allocation. One interesting feature of descriptive studies on dementia is that although the few epidemiologic studies conducted in Africa suggest that rates of dementia and AD are relatively low, rates of AD and dementia have been reported to be relatively high for African Americans. The Indianapolis-Ibadan Dementia Project has reported that the incidence rates for AD and dementia in Yoruba are less than half the incidence rates for AD and dementia in African Americans. Analytic studies are now underway to identify risk factors that may account for these rate differences. The risk factor model being applied, attempts to identify not only putative genetic and environmental factors but also their interactions. So far the major findings have included: apolipoprotein E e4, a major risk factor for AD in most populations, is also a risk factor for AD in African Americans but not for Yoruba; African Americans are at higher risk not only for AD, but also for diseases associated with increased cardiovascular risk such as hypertension, diabetes, and metabolic syndrome; African Americans have higher rates of hypercholesterolemia than Yoruba: there is an interaction between apolipoprotein E e4, cholesterol, and AD risk in both Yoruba and African Americans. We eventually hope to create a risk factor model that will not only account for the dementia rate differences between Yoruba and African Americans, but also help explain dementia rates in other developing and developed countries.

Risk factors for incident Alzheimer's disease in African Americans and Yoruba

AbstractIntroduction: The incidence rate of Alzheimers disease (AD) was found to be 2 times lower in Yoruba than in African Americans. This study was aimed at identifying the factors associated with increased risk of incident AD in the two communities. Methodology: A two-stage design with initial screening using the CSI’D followed by neuropsychological test battery, relations’ interview and physician assessment in a sub-sample.NINCDS-ADRDA criteria were met for AD. The risk factor variables assessed included demographic, lifestyle, medical and family history items. Results: In the Yoruba, AD was associated with age (OR = 1.07) and female gender (OR = 2.93). In African Americans, age (OR = 1.09) and rural living (OR = 2.08) were the significant risk factors, while alcohol was protective (OR = 0.49). Discussion: Age was a significant risk factor for AD at both sites. The higher risk of incident AD in the Yoruba female, and in African Americans who resided in rural areas in childhood were similar with the prevalence cases. Alcohol emerged a protective factor in African Americans. More studies are required, including biological measurements, to adequately explain the differences in rates.

The development of a semi-structured home interview (CHIF) to directly assess function in cognitively impaired elderly people in two cultures.

BACKGROUND Assessing function is a crucial element in the diagnosis of dementia. This information is usually obtained from key informants. However, reliable informants are not always available. METHODS A 10-item semi-structured home interview (the CHIF, or Clinician Home-based Interview to assess Function) to assess function primarily by measuring instrumental activities of daily living directly was developed and tested for inter-rater reliability and validity as part of the Indianapolis-Ibadan dementia project. The primary validity measurements were correlations between scores on the CHIF and independently gathered scores on the Blessed Dementia Scale (from informants) and the Mini-mental State Examination (MMSE). Sensitivities and specificities of scores on the CHIF and receiver operator characteristic (ROC) curves were constructed with dementia as the dependent variable. RESULTS Inter-rater reliability for the CHIF was high (Pearsons correlation coefficient 0.99 in Indianapolis and 0.87 in Ibadan). Internal consistency, in both samples, was good (Cronbachs alpha 0.95 in Indianapolis and 0.83 in Ibadan). Scores on the CHIF correlated well with the Blessed Dementia scores at both sites (-0.71, p < 0.0001 for Indianapolis and -0.56, p < 0.0001 for Ibadan) and with the MMSE (0.75, p < 0.0001 for Indianapolis and 0.44, p < 0.0001 for Ibadan). For all items at both sites, the subjects without dementia performed significantly better than those with dementia. The area under the ROC curve for dementia diagnosis was 0.965 for Indianapolis and 0.925 for Ibadan. CONCLUSION The CHIF is a useful instrument to assess function directly in elderly participants in international studies, particularly in the absence of reliable informants.