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Context: Alzheimer disease (AD) represents a major and increasing public health problem. If populations were identified with significantly lower or higher incidence rates of AD, the search for risk factors in the genesis of AD could be greatly enhanced.Objective: To compare incidence rates of dementia and AD in 2 diverse, elderly community-dwelling populations.Design: The Indianapolis-Ibadan Dementia Project, a longitudinal, prospective population-based study consisting of a baseline survey (1992-1993) and 2 subsequent follow-up waves after 2 years (1994-1995) and 5 years (1997-1998). Each wave followed a 2-stage design, with an in-home screening interview followed by a full diagnostic workup of a subsample of participants based on screening performance.Setting and Participants: A total of 2459 community-dwelling Yoruba residents of Ibadan, Nigeria, without dementia, and 2147 community-dwelling African American residents of Indianapolis, Ind, without dementia (all aged 65 years or older). The cohorts were followed up for a mean of 5.1 years and 4.7 years, respectively.Main Outcome Measures: Incident cases of dementia and AD in each of the 2 populations.Results: The age-standardized annual incidence rates were significantly lower among Yoruba than among African Americans for dementia (Yoruba, 1.35% [95% confidence interval [CI], 1.13%-1.56%]; African Americans, 3.24% [95% CI, 2.11%-4.38%]) and for AD (Yoruba, 1.15% [95% CI, 0.96%-1.35%]; African Americans, 2.52% [95% CI, 1.40%-3.64%]).Conclusion: This is the first report of incidence rate differences for dementia and AD in studies of 2 populations from nonindustrialized and industrialized countries using identical methods and the same group of investigators in both sites. Further explorations of these population differences may identify potentially modifiable environmental or genetic factors to account for site differences in dementia and AD. [ABSTRACT FROM AUTHOR]

Essentials Cognitive disorders are increasing and vascular risk factors play a role in this. We performed a nested case control study of hemostasis biomarkers and cognitive impairment (CI). Higher baseline fibrinogen, factor VIII and D-dimer were related to incident CI over 3.5 years. Adjusted for other risk factors, 2+ abnormal markers (but not single ones) led to higher risk., Summary: Background Vascular risk factors are associated with cognitive impairment, a condition that imposes a substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with the risk of incident cognitive impairment. Methods We performed a nested case-control study including 1082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30 239 black and white Americans aged ≥ 45 years. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII and protein C levels were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on two or more of three cognitive tests) and 587 controls. Results Unadjusted odds ratios (ORs) for incident cognitive impairment were 1.32 (95% confidence interval [CI] 1.02-1.70) for D-dimer > 0.50 μg mL -1 , 1.83 (95% CI 1.24-2.71) for fibrinogen > 90th percentile, 1.63 (95% CI 1.11-2.38) for FVIII > 90th percentile, and 1.10 (95% CI 0.73-1.65) for protein C < 10th percentile. There were no differences in associations by race or region. Adjustment for demographic, vascular and health behavior risk factors attenuated these associations. However, having at least two elevated biomarkers was associated with incident cognitive impairment, with an adjusted OR of 1.73 (95% CI 1.10-2.69). Conclusion Elevated D-dimer, fibrinogen and FVIII levels were not associated with the occurrence of cognitive impairment after multivariable adjustment; however, having at least two abnormal biomarkers was associated with the occurrence of cognitive impairment, suggesting that the burden of these biomarkers is relevant., (© 2018 International Society on Thrombosis and Haemostasis.)

Recent epidemiological data, mainly from cross-cultural studies, have revealed that the burden of dementia and Alzheimer's disease (AD) the most common type, is significantly lower in developing than in the industrialized countries. Caring for individuals with dementia is a major consideration because most developing countries do not have the resources to provide comprehensive care in institutions. Home care that is practiced is ideal given the cultural scenario especially with the extended family support. Public policies on the care of the elderly however need to be well articulated and implemented. Hypertension was the most frequent medical co-morbidity of the demented subjects and about a third of subjects with AD were hypertensive, which may support vascular hypothesis in AD pathogenesis. The important behavioural disturbances experienced by caregivers and the associated stress levels were highlighted. The model used on the Indianapolis-Ibadan Dementia Study which involves periodic home visits, and empowerment of caregivers through regular meetings is envisaged to make caring for these individuals easier and adaptable in other African communities.

We report clinical, neuropathologic and molecular genetic data from an individual affected by a familial Alzheimer disease (AD) variant. The proband had an onset of dementia at age 29 followed by generalized seizures a year later. He died at age 40. Neuropathologically, he had severe brain atrophy and characteristic histopathologic lesions of AD. Three additional neuropathologic features need to be emphasized: 1) severe deposition of Abeta in the form of diffuse deposits in the cerebral and cerebellar cortices, 2) numerous Abeta deposits in the subcortical white matter and in the centrum semiovale, and 3) numerous ectopic neurons, often containing tau-immunopositive neurofibrillary tangles, in the white maner of the frontal and temporal lobes. A molecular genetic analysis of DNA extracted from brain tissue of the proband revealed a S169L mutation in the Presenilin 1 (PSEN1) gene. The importance of this case lies in the presence of ectopic neurons in the white matter, early-onset seizures, and a PSEN1 mutation. We hypothesize that the PSEN1 mutation may have a causal relationship with an abnormality in neuronal development.

We documented the pattern of medical illnesses in 613 elderly Nigerians (398 females and 215 males) resident in Idikan community in Ibadan city. Their ages ranged from 65 to 110 years with a mean of 76.2 years. Medical disorders diagnosed either singly or in combinations were diagnosed in 364 (59.4%) subjects and there was no gender association. Cardiovascular problems were the commonest and high blood pressure (27.8%) was the most frequent diagnosis. Only 5 of the hypertensive subjects were aware of that diagnosis and were on regular medications. The complications presented with included heart failure and stroke. Visual impairment (12.1%) mainly due to cataracts and osteoarthritis (6.7%) in that order were next in frequency. The most frequent neurological disorders were hearing impairment and movement disorders. The other conditions encountered were similar to the findings in previous studies in this environment, and the usual findings in studies focusing on this age-group in other countries. The presence of morbidity was significantly associated with increasing age and poor performance on screening. The latter increased the probability of being selected for clinical examination with detection of medical problems or could suggest associated cognitive impairment. The prevalence of systemic hypertension was not different from findings in other communities in people of similar age groups. This study emphasises the role of hypertension as a major cause of morbidity in this community and stresses the need for increased health awareness especially with regards to regular checking of blood pressure so as to avoid complications.

The CERAD Neuropsychological Battery, includes 7 measures: Verbal Fluency; Modified Boston Naming; Mini-Mental State: Word List Learning, Recall and Recognition; Constructional Praxis. It was originally developed to evaluate patients with a clinical diagnosis of Alzheimer's disease, but is increasingly used in epidemiological studies of the incidence and prevalence of dementia in the elderly. The current study reports norms for African American and White representative community residents 71 years of age and older in North Carolina, and compares performance with that of African Americans in Indianapolis and with Whites in the Monongahela Valley, Pennsylvania. For all 3 studies, increased education and younger age was related to better performance on each of the 7 measures. Sex differences, when present, tended to favor women. Although on average African Americans performed more poorly than Whites, with demographic characteristics controlled, no significant racial differences were found in the North Carolina sample. Both African American and White participants in North Carolina performed more poorly than their racial counterparts in the other 2 studies, possibly because of selection-induced differences in health and educational status. Nevertheless, the use of an identical evaluation battery, such as the CERAD neuropsychologic instrument, facilitates comparisons not otherwise possible, and should be encouraged.

Mutations in the Neuroserpin gene have been reported to cause familial presenile dementia. We describe a new family in which the S52R Neuroserpin mutation is associated with progressive myoclonus epilepsy in 2 siblings. The proband presented myoclonus and epilepsy at age 24, his brother and mother presented a similar disorder when they were 25. A clinical diagnosis of progressive myoclonus epilepsy was made on the proband and his brother. Skin and liver biopsies did not reveal the presence of cytological alterations in the proband. His neurological status worsened over the subsequent 19 yr during which he became demented and had uncontrollable seizures. He died at 43 yr of age from aspiration pneumonia. Neuropathologically, eosinophilic bodies, which were positive for periodic acid-Schiff and immunoreactive with antibodies against human neuroserpin, were present in the perikarya and cell processes of the neurons. They were found in large numbers in the cerebral cortex and substantia nigra and to a lesser extent, in most subcortical gray areas, spinal cord, and dorsal root ganglia. By electron microscopy, the intracytoplasmic bodies were contained within the membranes of the rough endoplasmic reticulum. Occasionally neuroserpin immunopositivity was seen throughout the cytoplasm, even without the presence of well-defined bodies. Our study characterizes for the first time the neuropathologic phenotype associated with hereditary progressive myoclonus epilepsy caused by the S52R Neuroserpin mutation.

Amyloid beta protein deposition in cortical and leptomeningeal vessels, causing the most common type of cerebral amyloid angiopathy, is found in sporadic and familial Alzheimer's disease (AD) and is the principal feature in the hereditary cerebral hemorrhage with amyloidosis, Dutch type. The presence of the Apolipopriotein E (APOE)-epsilon4 allele has been implicated as a risk factor for AD and the development of cerebral amyloid angiopathy in AD. We report clinical, pathological and biochemical studies on two APOE-epsilon4 homozygous subjects, who had senile dementia and whose main neuropathological feature was a severe and diffuse amyloid angiopathy associated with perivascular tau neurofibrillary pathology. Amyloid beta protein and ApoE immunoreactivity were observed in leptomeningeal vessels as well as in medium-sized and small vessels and capillaries in the parenchyma of the neocortex, hippocampus, thalamus, cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid beta protein was that terminating at residue Val40, as determined by immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown of tau-immunopositive cell processes was consistently present around blood vessels. DNA sequence analysis of the Amyloid Precursor Protein gene and Presenilin-1 (PS-1) gene revealed no mutations. In these APOE-epsilon4 homozygous patients, the pathological process differed from that typically seen in AD in that they showed a heavy burden of perivascular tau-immunopositive cell processes associated with severe amyloid beta protein angiopathy, neurofibrillary tangles, some cortical Lewy bodies and an absence of neuritic plaques. These cases emphasize the concept that tau deposits may be pathogenetically related to amyloid beta protein deposition.

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.

Objective: To determine the association between demographic, lifestyle and medical history factors to Alzheimer's disease (AD), we studied samples of two community dwelling populations with significantly different prevalence rates of AD in Indianapolis, USA (6.24%) and Ibadan, Nigeria (1.4%)., Methods: The samples were drawn from African-American community dwelling residents 65 years of age and over in Indianapolis, and Yoruba community-dwelling residents 65 years of age and over in Ibadan. A two-stage epidemiological design was used in which diagnosis of AD was by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria., Results: In Indianapolis, age (odds ratio [OR] = 1.16; 95% confidence interval [CI] = 1.11-1.21), family history of dementia (OR = 5.40; 95% CI = 1.99-14.62), low education (0-6 years, OR = 3.49; 95% CI = 1.06-11.48) and rural residence (OR = 2.49; 95% CI = 1.05-5.88) were associated with a higher risk of AD. In Ibadan, age (OR = 1.15; 95% CI = 1.12-1.18) and female gender (OR = 13.9; 95% CI = 3.85-50.28) were associated with a higher risk of AD., Conclusions: The remarkably similar odds ratios between age and AD between sites suggest that biological processes associated with ageing are essential elements in the development of AD but that genetic and environmental risk factors may alter age-specific rates. In our longitudinal study, we intend to investigate in more depth the interaction between these ageing, genetic and environmental factors.

Dementing disorders are found most commonly in the elderly. However, the approaches derived from the diagnosis and management of these patients exemplify principles which can equally well be applied to the management of psychiatric disorders in younger patients. These principles include the process of syndromic diagnosis, the need for multi-dimensional assessment, the recognition of the interaction of biological and psycho-social factors in the etiology and treatment of psychiatric symptoms and the crucial role of the family in the management of patients with dementia. In this paper these principles are discussed.

In this study of 138 elderly subjects (112 without and 26 with dementia) obtained from a community sample of elderly African-American subjects, there were no significant differences in mean Geriatric Depression Scale scores by Apo E epsilon 4 status for dementia or nondementia subjects. Three subjects received a diagnosis of major depressive disorder. None of these subjects were Apo E epsilon 4-positive. These results do not support an association between depressive symptoms and Apo E allele status in this elderly African-American population.

Three patients with Gerstmann-Sträussler-Scheinker disease (GSS) caused by a serine-for-phenylalanine substitution at codon 198 of the prion protein gene (PRNP) were compared to 9 age- and education-matched non-mutation-carriers from the same large Indiana kindred (GSS-IK) on a comprehensive neuropsychological test battery. Clinically significant impairments in intelligence, secondary memory, attention and cognitive processing speed, executive ability, and manual motor skills were noted in 2 patients. The wide range and the severity of the cognitive deficits indicated generalized cerebral dysfunction consistent with global dementia. One patient, symptomatic for less than 1 year, had more selective deficits involving memory, motor skills, and verbal fluency, suggesting early subcortical involvement.

Objective: To report on moderate alcohol consumption and measurements of cognitive function and activities of daily living in an older, urban, community-dwelling sample of black Americans., Design: As part of a community prevalence study of dementia, information on alcohol consumption and cognitive performance was collected on 2040 randomly selected black subjects living in Indianapolis., Measurements: From questions in the screening interview, alcohol consumption was grouped into four categories: lifetime abstainers, regular drinkers less than 4 drinks per week, 4 to 10 drinks per week, and more than 10 drinks per week. Current and past drinkers were analyzed separately. Three measurements were used: (1) a total cognitive score; (2) the delayed recall score from the East Boston Memory Test; (3) a score for daily functioning based upon information from the informant. Multiple regression models were fitted with drinking variables as the major predictor, including covariates of age, gender, education, history of stroke, hypertension, being treated for depression, and a family history of dementia., Main Results: In all analyses, there was a very consistent pattern for both current and past drinkers. There was a small but significant dose effect of drinking for the drinkers, with subjects in the heaviest drinking category scoring poorest, i.e., lowest scores in cognitive tests and highest scores in scales of daily functioning indicating more impairment. The scores of abstainers were worse than those of subjects in the lightest drinking category. The pattern of scores for cognitive performance and daily functioning was similar between current and past drinkers. These patterns remained the same even after potential confounders were included., Conclusions: Previous research on effects of alcohol on health indices have suggested a J-shaped relationship between amounts of alcohol consumption and measurements of heart disease, stroke, and mortality rates. Our study provides some support for the concept of a similar J-shaped relationship between cognitive performance and alcohol consumption, but the differences between drinking categories were modest and the clinical significance of these findings uncertain.

Objective: High prevalence rates of psychiatric illness and high levels of behavioral disturbance have been reported in studies of nursing home residents; however, the populations evaluated have been predominantly Caucasian. The aims of the present study were to identify prevalence rates of psychiatric disorders and behavioral disturbances in a sample of African American nursing home residents., Methods: The authors evaluated 106 African American nursing home residents, aged 65 and over, from a representative sample of nursing homes. The evaluation included informant interview with nursing home staff, cognitive assessment, and a psychiatric interview that included a physical and neurological examination. Consensus diagnoses were reached by using DSM-III-R criteria., Results: Of the 106 subjects, 90% received at least one primary psychiatric diagnosis, and 71% had at least one behavioral problem; dementia was the most common psychiatric diagnosis (68%). Thirty -one percent of the patients were treated with neuroleptic medication; most of these patients received diagnoses of dementia or schizophrenia. Fifteen percent of the patients had been in physical restraints, which correlated with physical disability., Conclusions: The prevalence of psychiatric illness in this sample of African American nursing home residents is similar to that reported in previous studies with predominantly Caucasian populations. Behavioral disturbances, while commonly reported, were somewhat less frequent than reported in previous studies.