Valerie Smith-Gamble

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.

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.

APOE ε4 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 Alzheimers 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 Alzheimers disease. In contrast with other populations, the APOE ε4 allele was not significantly associated with Alzheimers disease or dementia. This lack of association in the Yoruba might reflect genetic variation, environmental factors, as well as genetic/environmental interactions. Ann neurol 2006

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

This study compares age‐specific and overall prevalence rates for dementia and Alzheimers disease (AD) in two nonoverlapping, population‐based cohorts of elderly African Americans in Indianapolis in 2001 and 1992.

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.

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.

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.

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.

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.

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.