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There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer's disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline.
In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox's proportional hazards regression and mixed effects models.
After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425).
In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.
High levels of homocysteine have been associated with increased risk for dementia although results have been inconsistent. There are no reported studies from the developing world including Africa.
In this longitudinal study of two community-dwelling cohorts of elderly Yoruba and African Americans, levels of homocysteine, vitamin B12 and folate were measured from blood samples taken in 2001. These levels were compared in two groups, participants who developed incident dementia in the follow-up until 2009 (59 Yoruba and 101 African Americans) and participants who were diagnosed as cognitively normal or in the good performance category at their last follow-up (760 Yoruba and 811 African Americans). Homocysteine levels were divided into quartiles for each site.
After adjusting for age, education, possession of ApoE, smoking, and time of enrollment the higher quartiles of homocysteine were associated with a non-significant increase in dementia risk in the Yoruba (homocysteine quartile 4 vs. 1 OR: 2.19, 95% CI 0.95–5.07, p = 0.066). For the African Americans, there was a similar but non-significant relationship between higher homocysteine levels and dementia risk. There were no significant relationships between levels of vitamin B12 and folate and incident dementia in either site although folate levels were lower and vitamin B12 levers were higher in the Yoruba than in the African Americans.
Increased homocysteine levels were associated with a similar but non-significant increase in dementia risk for both Yoruba and African Americans despite significant differences in folate levels between the two sites.
Se is an antioxidant micronutrient and has been studied for its potential role in CVD prevention. The purpose of the present study was to conduct a systematic review of the literature on the relationship between Se and hypertension.
We conducted a systematic literature search in PubMed and OVID of studies on Se levels and hypertension or blood pressure published in English up to June 2011. Articles meeting inclusion criteria were reviewed and the following information was gathered from each publication: study setting, participant demographics, exclusion criteria, intervention if applicable, medium of Se measure, mean level of Se, outcome definition, relationship between Se and the outcome variable, significance of this relationship, and covariates. In studies that also reported glutathione peroxidase levels, we extracted results on the relationship between glutathione peroxidase and hypertension.
Twenty-five articles were included. Approximately half of the studies reported no significant relationship between Se and hypertension. Of the remaining studies, about half found that higher Se levels were associated with lower blood pressure and the other half found the opposite relationship. The studies varied greatly in terms of study population, study design and Se levels measured in participants.
Based on the present systematic review, there is no conclusive evidence supporting an association between Se and hypertension. Randomized controlled trials and prospective studies with sufficient sample size in populations with different Se levels are needed to fully investigate the relationship between Se and hypertension.
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.
Se is an essential trace element in human nutrition associated with antioxidant activity. Previous studies on predictors of toenail Se or serum Se have mostly concentrated on demographic factors such as age and gender. The present paper examines the association between apoE genotype and Se levels in nail samples in a rural elderly Chinese cohort.
Two thousand Chinese aged 65 years and over from four counties in China were enrolled in a cohort to study the association of Se with cognitive decline. Nail samples were collected from each participant and analysed for Se levels. Dietary Se intake was estimated from an FFQ using Se contents measured in food items collected from each village. Blood samples on filter cards were collected and analysed for apoE genotype. Mixed-effect models were constructed with nail Se level as the dependent variable and each village as the random effect, which controlled for the potential confounding effect from correlation in Se measures obtained from participants residing in the same village.
In this elderly Chinese cohort, carriers of the apoE ε4 allele had significantly lower Se levels measured in nail samples than non-carriers after adjusting for other significant covariates and controlling for estimated dietary Se intake. There was no significant difference between the two genotypes on estimated Se dietary intake (P = 0·6451).
Future studies are needed to examine the mechanism underlying the association between the apoE ε4 allele and Se levels, including the role of oxidative stress and that of reduced lipid metabolism in the apoE ε4 carriers.
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.
Visuoconstructional ability is an important domain for assessment in
dementia. Use of graphomotor measures dominate this area; however,
participants with low education produce results that cannot be easily
interpreted. Our objective was to develop and validate a nongraphomotor
assessment of visuoconstructional ability for use in dementia evaluations
in persons with low or no education. In a longitudinal, population-based
study of dementia among Yoruba residents of Ibadan, Nigeria aged 65 years
and older, participants underwent clinical assessment with a battery of
cognitive tests and consensus diagnosis. Performance on two
visuoconstructional tests, Constructional Praxis and Stick Design, were
compared. Gender, age, and education affected performance on both tests.
The Stick Design test was more acceptable than Constructional Praxis as
measured by the number of participants with total test failure (3.9%
vs. 15.1%). The Stick Design test was significantly more
sensitive to cognitive impairment and dementia than the Constructional
Praxis test. We conclude that Stick Design is a reasonable test of
visuoconstructional ability in older cohorts with very limited educational
exposure and literacy. (JINS, 2005, 11,
Comparative cross-cultural studies represent a great opportunity for delineating risk factors for the dementias by providing a much wider diversity of both environmental exposures and genetic variation than studies within industrialized countries. Similarly, studies of the behavioral disturbances of dementia that allow for identification of similarities and differences may be useful both in understanding the etiology of these disorders and in determining the best approach to management. So far, few such comparative studies exist.
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.
Dementia with Lewy bodies (DLB) is the second most common neuropathologically diagnosed cause of degenerating dementia after Alzheimer's disease. We report the first autopsy-confirmed case in sub-Saharan Africa in a Nigerian patient. The case presented highlights the varied clinical presentation of DLB, and is intended to raise awareness about another possible cause of dementia in Nigerian subjects.
A community survey and subsequent clinical assessment of 192 Cree aged 65 years and over registered in two Reserves in Northern Manitoba identified only one case of probable Alzheimer's disease among eight cases of dementia, giving a prevalence of 0.5% for Alzheimer's disease and 4.2% for all dementias. This contrasted with an age-adjusted prevalence of 3.5% for Alzheimer's disease and 4.2% for all dementias in an age-stratified sample of 241 English-speaking residents of Winnipeg. Although it was not so for all dementias, the difference between the groups for prevalence of Alzheimer's disease was highly significant (p < .001). The age-specific patterns of all dementias in the two groups were significantly different, however (p = .0254).
Studying behavioral disturbances of dementia across cultures allows us to identify commonalities and differences that may be useful in determining the best approach to managing these problems. However, what we tend to find in cross-cultural studies is that the best approach may not be the same approach, given the different prevalence of and levels of tolerance for various behavioral problems. These differences are apparent in the authors' studies of four populations—Jamaicans in Kingston; Cree in Northern Manitoba, Canada; Yoruba in Ibadan, Nigeria; and African Americans in the United States. The Jamaicans in this study live in a poor suburb of Kingston, the Cree live in two fairly small, isolated communities in Northern Manitoba, and the Yoruba live in Ibadan, a city of more than 1 million people. The Yoruba community the authors are studying, although concentrated in the city center, functions much like a village. The African-American population resides in Indianapolis, Indiana, a moderately sized city of approximately 1 million people.
Damage to, or deterioration of, the keratinized horn tissue of the bovine hoof claw culminates ultimately in the development of solear ulceration. We have observed abnormal keratin distribution at the site of solear ulceration in the bovine claw that may be due to alteration of the positional cues of the keratinocytes. In this study we have characterized key cell biological changes associated with ulceration in the claw that may precipitate abnormal keratinization. Loss of basement membrane at sites of ulceration was found by immunofluorescent detection of laminin and integrins. In other tissues, basement membrane breakdown results from degradation by matrix metalloproteinases (MMPs). Similarly, elevated levels of MMPs 2 and 9 were observed in ulcerated bovine claw tissue both by zymography and, quantitatively, by assay of enzyme activity. In the sole of claws that contained an ulcer, tissue distal to the ulcer site also had elevated MMP 2 when compared with healthy sole tissue from the same animals, as did sole tissue of claws recovering from ulceration. Tissue inhibitor of metalloproteinase 2 (TIMP 2) was detected by ELISA in healthy tissue. TIMP 2 tended to be lower in diseased tissue distal to ulcer sites, and was significantly lower in ulcerated tissue. MMP 2 was located by immunofluorescence in the dermal and basal epidermal region of sole tissue, in the region of the basement membrane. Increased punctate staining of material in the dermis was associated with ulcerated material. ELISA of TIMP 2 in tissue extracts enriched for dermis or epidermis confirmed that the inhibitor was located predominantly in the dermis. To investigate a possible causal relationship between basement membrane anchorage and epidermal keratinization, the effect of function-blocking antibodies to laminins and integrins was tested in tissue explant cultures prepared from healthy sole tissue. Anti-integrin antibody treatment had no effect on either protein or DNA synthesis. In contrast, in the presence of anti-laminin antibody, protein synthesis was decreased in a concentration-dependent manner, a significant effect being observed at the highest concentration after treatment for 24 h. At this concentration, DNA synthesis was also decreased after 48 h of culture, an effect that may be relevant to a hibernal reduction in claw cell turnover, and the associated seasonal vulnerability of cows to claw damage. The results provide evidence for basement membrane disruption at ulcer sites, and an increased potential for disruption in the diseased claw, and a causal link between this and abnormal epidermal keratinization. Basement membrane disruption is in turn associated with reciprocal changes in MMPs and their inhibitors, favouring extracellular proteolysis. Whether MMP activation is the primary cause of dermal–epidermal deterioration and, if so, how MMP activation is triggered, remains to be determined.
Information on the clinical utility of neuropsychological
tests in non-North-American samples is limited. We examined
the diagnostic efficacy of the Consortium to Establish
a Registry for Alzheimer's Disease (CERAD) neuropsychological
battery in Jamaican men and women age 65 and older. A total
of 72 elders were diagnosed as normal and 12 were demented
based on history, physical, and neurological examination.
Independent of this medical examination, participants were
tested with the CERAD battery. Normal controls scored significantly
better than dementia patients on all tests in the CERAD
battery. A discriminant function found that a combination
of Word List Learning Sum Recall and Boston Naming Test
correctly classified a total of 81% of the cases (83% of
the dements and 81% of the normal controls). This study
is the first to demonstrate the clinical utility of the
CERAD neuropsychological battery in the differential diagnosis
of memory disorders of the aged in a non-North-American
sample. (JINS, 1999, 5, 255–259.)