Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans.

OBJECTIVE: To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. DESIGN: Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. SETTING: Indianapolis, Indiana. PARTICIPANTS: From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. MAIN OUTCOME MEASURES: Incident dementia and incident AD. RESULTS: After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. CONCLUSIONS: Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.

Mild cognitive impairment, incidence, progression, and reversion: findings from a community-based cohort of elderly African Americans.

OBJECTIVE: To examine the long-term outcomes of community-based elderly African Americans by following their transitions from normal cognition to mild cognitive impairment (MCI) to dementia. METHODS: Participants were from the community-based Indianapolis Dementia Project. A total of 4,104 African Americans were enrolled in 1992 or 2001 and followed until 2009 with regularly scheduled evaluation of cognitive assessment. A two-stage sampling was used at each evaluation to select individuals for extensive clinical assessment following the results of Stage 1 cognitive testing. Age- and gender-specific incidence, progression, and reversion rates for MCI were derived using the person-year method in a dynamic cohort and predicted probabilities from weighted multinomial logistic models of transitional probabilities among normal cognition, MCI, and dementia. RESULTS: Annual overall incidence rate for MCI was 5.6% (95% confidence interval [CI]: 4.6%-6.6%). Annual progression rate from MCI to dementia was 5.9% (95% CI: 5.3%-6.5%), and annual reversion rate from MCI to normal was 18.6% (95% CI: 16.7%-20.4%). Both MCI incidence rates and MCI to dementia progression rates increased with age, whereas reversion rates from MCI to normal decreased with age. CONCLUSION: MCI progression to dementia was much more frequent in the older age groups than in younger participants where reversion to normal cognition is more common. Future research is needed to determine factors related to the heterogeneous outcomes in MCI individuals.

Behavioral symptoms in community-dwelling elderly Nigerians with dementia, mild cognitive impairment, and normal cognition.

BACKGROUND: Few studies have examined the neuropsychiatric status of patients with dementia and cognitive impairment in the developing world despite the fact that current demographic trends suggest an urgent need for such studies. OBJECTIVE: To assess the level of neuropsychiatric symptoms in community-dwelling individuals with dementia, cognitive impairment no dementia and normal cognition. METHODS: Subjects were from the Ibadan site of Indianapolis-Ibadan Dementia Project with stable diagnoses of normal cognition, cognitive impairment, no dementia/mild cognitive impairment (CIND/MCI), and dementia. Informants of subjects made ratings on the neuropsychiatric inventory and blessed dementia scale; subjects were tested with the mini mental state examination. RESULTS: One hundred and eight subjects were included in the analytic sample, 21 were cognitively normal, 34 were demented, and 53 were CIND/MCI. The diagnostic groups did not differ in age, per cent female, or per cent with any formal education. The most frequent symptoms among subjects with CIND/MCI were depression (45.3%), apathy (37.7%), night time behavior (28.3%), appetite change (24.5%), irritability (22.6%), delusions (22.6%), anxiety (18.9%), and agitation (17.0%). Depression was significantly more frequent among the CIND/MCI and dementia (44.1%) groups compared with the normal cognition group (9.5%). Distress scores were highest for the dementia group, lowest for the normal cognition group, and intermediate for the CIND/MCI group. CONCLUSION: Significant neuropsychiatric symptomatology and distress are present among cognitively impaired persons in this community-based study of older adults in this sub-Saharan African country. Programs to assist family members of cognitively impaired and demented persons should be created or adapted for use in developing countries.

Incidence and risk factors for cognitive impairment no dementia and mild cognitive impairment in African Americans.

The aim of this study was to estimate the age-specific incidence of cognitive impairment, no dementia and mild cognitive impairment (CIND/MCI) in a large, community-based sample of older African Americans in Indianapolis, IN. A longitudinal, prospective, 2-stage design was used with follow-up assessments 2 and 5 years after the baseline. A total of 1668 participants completed the 2-year follow-up and a total of 1255 participants completed the 5-year follow-up. The person-years method was used to calculate incidence rates. The age-standardized, annual incidence of CIND/MCI was 4.95% (CI=3.39-6.52) and the subtype of medically unexplained memory loss (single-domain and multidomain amnestic MCI) was 3.67% (CI 2.75-4.48). Rates increased with age (3.43% for participants aged 65 to 74 y, 6.44% from age 75 to 84 y, and 9.62% from age 85+ y), history of head injury [OR 2.37 (CI 1.31-4.29)], and history of depression [OR 2.22 (CI 1.16-4.25)] while increased years of schooling was protective [OR 0.91 (CI 0.85-0.97)]. Rates did not vary substantially by sex. Almost 1 in 20 elderly community-dwelling African Americans, and almost 1 in 10 of the oldest-old (85+ y) developed CIND/MCI each year in this cohort. Risk factors of age and education suggest exposures or mechanisms at both ends of the life span may be important variables in onset of CIND/MCI.

Weight loss and incident dementia in elderly Yoruba Nigerians: a 10-year follow-up study.

BACKGROUND: The relationship between weight and dementia risk has not been investigated in populations with relatively low body mass index (BMI) such as the Yoruba. This study set out to achieve this objective using a prospective observational design. METHODS: The setting was Idikan Ward in Ibadan City, Nigeria. The participants were all aged 65 years or older and were enrolled in the Indianapolis-Ibadan Dementia Project. Repeated cognitive assessments and clinical evaluations were conducted to identify participants with dementia or MCI during 10 years of follow-up (mean duration: 5.97 years). BMI measures, information on alcohol, smoking history, cancer, hypertension, diabetes, heart attack, stroke and depression were collected at each follow-up evaluation. Mixed effect models adjusted for covariates were used to examine the differences in BMI among participants who developed dementia or MCI and those who remained cognitively normal during the follow-up. RESULTS: This analysis included 1559 participants who had no dementia at their first BMI measurements. There were 136 subjects with incident dementia, 255 with MCI and 1168 with normal cognition by the end of the study. The mean BMI at baseline was higher for female participants (22.31; SD = 4.39) than for male (21.09; SD = 3.61, p < 0.001). A significantly greater decline in BMI was found in those with either incident dementia (p < 0.001) or incident MCI (p < 0.001) compared to normal subjects. CONCLUSION: Decline in BMI is associated with incident MCI and dementia in elderly Yoruba. This observation calls for close monitoring of weight loss in elderly individuals which may indicate future cognitive impairment for timely detection and tailored interventions.

Prevalence rates for dementia and Alzheimer's disease in African Americans: 1992 versus 2001.

BACKGROUND: This study compares age-specific and overall prevalence rates for dementia and Alzheimer's disease (AD) in two nonoverlapping, population-based cohorts of elderly African Americans in Indianapolis in 2001 and 1992. METHODS: We used a two-stage design. The first stage involves the Community Screening Interview for Dementia (CSI-D). The CSI-D scores are grouped into good, intermediate, and poor performance before selection for clinical assessment. Diagnoses were performed using standard criteria in a consensus diagnosis conference; clinicians were blind to performance groups. In 1992, interviewers visited randomly sampled addresses to enroll self-identified African Americans aged > or =65 years. Of 2582 eligible, 2212 enrolled (9.6% refused, and 4.7% were too sick). In 2001, Medicare rolls were used for African Americans aged >70 years. Of 4260 eligible, 1892 (44%) enrolled, 1999 (47%) refused, and the remainder did not participate for other reasons. RESULTS: The overall age-adjusted prevalence rate for dementia at age > or =70 years in 2001 was 7.45% (95 confidence interval [CI], 4.27-10.64), and in the 1992 cohort, this prevalence rate was 6.75% (95% CI, 5.77-7.74). The overall age-adjusted prevalence rate at age > or =70 years for AD in the 2001 cohort was 6.77% (95% CI, 3.65-9.90), and for the 1992 cohort, it was 5.47% (95% CI, 4.51-6.42). Rates for dementia and AD were not significantly different in the two cohorts (dementia, P = .3534; AD, P = .2649). CONCLUSIONS: We found no differences in the prevalence rates of dementia and AD between 1992 and 2001, despite significant differences in medical history and medical treatment within these population-based cohorts of African American elderly.

The Association of Early Life Factors and Declining Incidence Rates of Dementia in an Elderly Population of African Americans.

Objectives: To explore the possible association of childhood residence, education levels, and occupation with declining incidence rates of dementia in 2 cohorts of elderly African Americans. Methods: African Americans residing in Indianapolis without dementia were enrolled in 1992 and 2001 and evaluated every 2-3 years. The cohorts consist of 1,440 participants in 1992 and 1,835 participants in 2001 aged 70 years and older. Cox proportional hazard regression models were used to compare cohort differences in dementia and Alzheimer's disease (AD) risk. Results: The 2001 cohort had significantly decreased risk of both incident dementia and AD (hazard ratio [HR]: 0.62/0.57 for dementia/AD). Years of education was associated with decreased risk of dementia (HR = 0.93; p = .0011). A significant interaction (p = .0477) between education and childhood rural residence was found for the risk of AD that higher education level is significantly associated with reduced AD risk (HR = 0.87) in participants with childhood rural residence, but no association in those with urban upbringing. The cohort difference for dementia rates were attenuated by adjusting for the 3 risk factors but remained significant (HR = 0.75; p = .04). Discussion: These results emphasize the importance of early life factors including rural residence and education for the risk for dementia later in life.

Association of apolipoprotein E genotype and Alzheimer disease in African Americans.

BACKGROUND: Alzheimer disease (AD) is the most frequent cause of dementia. Even though the incidence of AD in the African American population is similar to or higher than that in persons of European descent, AD in African Americans is understudied. Identification of genetic risk factors in African Americans is essential for understanding the etiology of AD. OBJECTIVE: To determine the effect of apolipoprotein E (APOE) genotype on the risk of AD in elderly African Americans. DESIGN: Population-based longitudinal study of AD. SETTING: Indianapolis, Ind. PARTICIPANTS: African Americans 65 years and older. MAIN OUTCOME MEASURES: APOE genotype and diagnosis of AD. RESULTS: The APOE genotype was determined in 1822 samples. Of these, 690 were clinically evaluated: 318 were normal, and 162 had a diagnosis of AD. The presence of APOE epsilon4 was significantly associated with increased risk of AD (epsilon3/epsilon4: OR, 2.32; 95% confidence interval [CI], 1.41-3.82; and epsilon4/epsilon4: OR, 7.19; 95% CI, 3.00-17.29, compared with the epsilon3/epsilon3 genotype). There was also a significant protective effect with APOE epsilon2 (epsilon2/epsilon2 and epsilon2/epsilon3: OR, 0.42; 95% CI, 0.20-0.89). CONCLUSIONS: These findings are in marked contrast to the lack of association between APOE and AD in the Ibadan, Nigeria, sample of this project. These results suggest that other genetic factors and different environmental influences may play a role in the risk for AD in individuals of African ancestry.

Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial.

CONTEXT: Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug. OBJECTIVE: To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia. DESIGN AND SETTING: Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers. PARTICIPANTS: Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments. INTERVENTIONS: Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159); or haloperidol, 5 to 20 mg/d (n = 150), for 12 months. MAIN OUTCOME MEASURES: Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients). RESULTS: There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from 3000 dollars to 9000 dollars annually. Differences in societal costs were somewhat smaller and were not significant. CONCLUSION: Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost.

Accelerated weight loss and incident dementia in an elderly African-American cohort.

OBJECTIVES: To examine the association between changes in body mass index (BMI), dementia, and mild cognitive impairment (MCI). DESIGN: Prospective observational study. SETTING: Urban community in Indianapolis, Indiana. PARTICIPANTS: Participants were African Americans aged 65 and older enrolled in the Indianapolis Dementia Project and followed through 2007. This analysis included 1,331 participants who did not have dementia at their first BMI measurement. MEASUREMENTS: Cognitive assessment and clinical evaluations were conducted every other year to identify participants with dementia or MCI during 12 years of follow-up (mean follow-up 6.4 years). BMI measures; alcohol and smoking history; and medical conditions including history of cancer, hypertension, diabetes mellitus, heart attack, stroke; and depression were collected at each follow-up evaluation. Mixed-effect models were used to examine the differences in BMI between participants who developed dementia or MCI and those who did not, adjusting for covariates. RESULTS: Mean BMI at baseline was 29.8 ± 5.7 for women and 28.3 ± 4.8 for men. Participants with incident dementia or MCI had greater decline in BMI than those without (P=.02 for dementia, P=.04 for MCI). BMI in participants with incident dementia, MCI, and normal cognition did not differ 12 or 9 years before diagnosis, but 6 years before diagnosis, participants with incident dementia had significantly lower BMI than participants with normal cognition (P=.03), as did participants with MCI (P=.006). CONCLUSION: Decline in BMI appears to be an early marker for dementia. There is a need for the close monitoring of weight loss in older adults.

Prevalence estimates of depression in elderly community-dwelling African Americans in Indianapolis and Yoruba in Ibadan, Nigeria.

BACKGROUND: This is a community-based longitudinal epidemiological comparative study of elderly African Americans in Indianapolis and elderly Yoruba in Ibadan, Nigeria. METHOD: A two-stage study was designed in which community-based individuals were first screened using the Community Screening Interview for Dementia. The second stage was a full clinical assessment, which included use of the Geriatric Depression Scale, of a smaller sub-sample of individuals selected on the basis of their performance in the screening interview. Prevalence of depression was estimated using sampling weights according to the sampling stratification scheme for clinical assessment. RESULTS: Some 2627 individuals were evaluated at the first stage in Indianapolis and 2806 in Ibadan. All were aged 69 years and over. Of these, 451 (17.2%) underwent clinical assessment in Indianapolis, while 605 (21.6%) were assessed in Ibadan. The prevalence estimates of both mild and severe depression were similar for the two sites (p=0.1273 and p=0.7093): 12.3% (mild depression) and 2.2% (severe depression) in Indianapolis and 19.8% and 1.6% respectively in Ibadan. Some differences were identified in association with demographic characteristics; for example, Ibadan men had a significantly higher prevalence of mild depression than Indianapolis men (p<0.0001). Poor cognitive performance was associated with significantly higher rates of depression in Yoruba (p=0.0039). CONCLUSION: Prevalence of depression was similar for elderly African Americans and Yoruba despite considerable socioeconomic and cultural differences between these populations.

APOE epsilon4 is not associated with Alzheimer's disease in elderly Nigerians.

Since 1992, research teams from Indiana University and the University of Ibadan have been collecting and comparing data from two diverse, elderly populations to identify risk factors for dementia and Alzheimer's disease. Apolipoprotein E (APOE) was genotyped in 2,245 Nigerian samples. Of these, 830 had a diagnosis: 459 were normal, and 140 had dementia including 123 diagnosed with Alzheimer's disease. In contrast with other populations, the APOE epsilon4 allele was not significantly associated with Alzheimer's disease or dementia. This lack of association in the Yoruba might reflect genetic variation, environmental factors, as well as genetic/environmental interactions.

Informant reports of changes in personality predict dementia in a population-based study of elderly african americans and yoruba.

OBJECTIVE: The authors conducted a longitudinal, population-based survey of African Americans in Indianapolis, Indiana, and Yoruba in Ibadan, Nigeria, using the Community Screening Interview for Dementia to assess the predictive value of informant reports of changes in personality on incident dementia and Alzheimer disease. METHODS: In all, 3,021 subjects had informants' reports of changes in personality and dementia status (2,084 subjects residing in Ibadan and 937 subjects residing in Indianapolis). RESULTS: After adjusting for demographic, cognitive, and functional characteristics in two markedly different populations, socioeconomically and culturally, subjects with changes in personality had approximately twice the odds of having dementia as subjects with no change in personality. CONCLUSION: The finding that in two markedly different populations, personality change is a significant predictor of future dementia, independent of cognition and functional status, should make clinicians particularly sensitive to these reports when they occur in their elderly patients.

Behavioral and caregiver reaction of dementia as measured by the neuropsychiatric inventory in Nigerian community residents.

BACKGROUND: The Neuropsychiatric Inventory (NPI) has been used to assess behavioral symptoms of dementia in the United States, Taiwan, Japan, and Italy. METHOD: This report evaluates the use of the NPI to assess behavioral symptoms of dementia in a population of Yoruba, Nigerians aged 65 years and older who are subjects in the Indianapolis-Ibadan Dementia Project. In this study, the NPI, Blessed Dementia Scale, and Mini-Mental State Examination (MMSE) were used to assess Nigerian subjects with dementia. For this study the NPI was translated, back translated, and harmonized into Yoruba. RESULTS: The harmonized version of the NPI showed good interrater and test-retest reliability. The Cronbach alpha on 40 subjects was .80 for total severity score, .73 for frequency, and .73 for distress, indicating good internal consistency. The MMSE correlated with the NPI total score and severity scores of delusion, hallucination, and agitation, whereas the Blessed correlated with the NPI total score and severity scores of depression, anxiety, and nighttime behavior. CONCLUSIONS: The NPI was found to be a reliable tool to assess behavioral symptoms and caregiver distress of dementia in the Yoruba. Behavioral disturbances were as common in the Yoruba patients with dementia as in studies in other countries that have used the NPI, but the pattern of behavioral disturbances and caregiver response varied among the countries.