Biomedical subjects

F W Unverzagt

Publications and source records attributed to F W Unverzagt.

At least 19 recordsLinked to original sources

PubMed2006

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

INTRODUCTION: The incidence rate of Alzheimer's 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.

Black or African American↗

PubMed2006

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 (Pearson's correlation coefficient 0.99 in Indianapolis and 0.87 in Ibadan). Internal consistency, in both samples, was good (Cronbach's 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.

Activities of Daily Living↗

PubMed2006

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-Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Logistic regression models showed interaction after adjusting for age and gender between APOE-epsilon4 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-epsilon4 allele, but not in those with APOE-epsilon4. There was no significant association between levels of triglycerides and AD risk in those without APOE-epsilon4. CONCLUSIONS: There was a significant interaction between cholesterol, APOE-epsilon4, 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.

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PubMed2002

Cognitive impairment in community-dwelling older Nigerians: clinical correlates and stability of diagnosis.

To determine correlates and outcome of cognitive impairment without dementia in community-dwelling elderly Nigerians. A total of 2487 community residents aged 65 years and over were screened using the Community Screening Interview for Dementia. A subset of 423 individuals received diagnostic clinical evaluation. Participants were diagnosed normal, demented, or cognitive impairment no dementia (CIND). Follow-up clinical diagnostic evaluation was conducted on CIND subjects approximately 2 years later. One hundred and fifty-two persons were diagnosed CIND. Eighty-seven CIND subjects were seen at follow-up assessment, 14 (16.1%) had converted to dementia, 22 (25.3%) reverted to normal, and 51 (58.6%) remained CIND. No baseline factors predicted later development of dementia amongst the CIND subjects. CIND subjects who reverted to normal tended to be male and to have higher baseline cognitive scores. Apolipoprotein status was not related to diagnosis at follow-up. CIND is common in community-dwelling Nigerians. Although the outcome is variable, it does represent a high-risk group for subsequent dementia.

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PubMed2001

Prevalence of cognitive impairment: data from the Indianapolis Study of Health and Aging.

BACKGROUND: The epidemiology and natural history of cognitive impairment that is not dementia is important to the understanding of normal aging and dementia. OBJECTIVE: To determine the prevalence and outcome of cognitive impairment that is not dementia in an elderly African American population. METHOD: A two-phase, longitudinal study of aging and dementia. A total of 2212 community-dwelling African American residents of Indianapolis, IN, aged 65 and older were screened, and a subset (n = 351) received full clinical assessment and diagnosis. Subsets of the clinically assessed were seen again for clinical assessment and rediagnosis at 18 and 48 months. Weighted logistic regression was used to generate age-specific prevalence estimates. RESULTS: The overall rate of cognitive impairment among community-dwelling elderly was 23.4%. Age-specific rates indicate increasing prevalence with increasing age: 19.2% for ages 65 to 74 years, 27.6% for ages 75 to 84 years, and 38.0% for ages 85+ years. The most frequent cause of cognitive impairment was medically unexplained memory loss with a community prevalence of 12.5%, followed by medical illness-associated cognitive impairment (4.0% prevalence), stroke (3.6% prevalence), and alcohol abuse (1.5% prevalence). At 18-month follow-up, 26% (17/66) of the subjects had become demented. CONCLUSIONS: Cognitive impairment short of dementia affects nearly one in four community-dwelling elders and is a major risk factor for later development of dementia.

Age Distribution↗

PubMed2001

Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana.

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.

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PubMed2001

Performance of elderly African American and White community residents on the CERAD Neuropsychological Battery.

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.

Black or African American↗

PubMed2001

Ectopic white matter neurons, a developmental abnormality that may be caused by the PSEN1 S169L mutation in a case of familial AD with myoclonus and seizures.

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.

Adult↗

PubMed2000

Trace element levels in drinking water and cognitive function among elderly Chinese.

The relation between trace element levels in drinking water and cognitive function was investigated in a population-based study of elderly residents (n = 1,016) in rural China in 1996-1997. Cognitive function was measured using a Chinese translation of the Community Screening Interview for Dementia. A mixed effects model was used to evaluate the effect of each of the elements on cognitive function while adjusting for age, sex, and educational level. Several of the elements examined had a significant effect on cognitive function when they were assessed in a univariate context. However, after adjustment for other elements, many of these results were not significant. There was a significant quadratic effect for calcium and a significant zinc-cadmium interaction. Cognitive function increased with calcium level up to a certain point and then decreased as calcium continued to increase. Zinc showed a positive relation with cognitive function at low cadmium levels but a negative relation at high levels.

Age Distribution↗

PubMed2000

Low education and childhood rural residence: risk for Alzheimer's disease in African Americans.

OBJECTIVE: To examine the relationship between level of education and childhood rural residence as possible risk factors for AD in African Americans in Indianapolis. BACKGROUND: Low level of education has been a risk factor for AD in some studies, but childhood rural residence has not been addressed in most of these studies. METHODS: A two-stage community-based prevalence study of AD was conducted in a random sample of 2,212 African Americans > or =65 years of age. A subsample of clinically assessed normal individuals (180) and individuals diagnosed with AD (43) were compared on the variables of rural/urban residence in childhood and low (< or =6 years) or high (> or =7 years) education. A logistic regression model was used with interaction between rural residence and low education to estimate odds ratios for the two risk factors combined, adjusting for age and gender. RESULTS: Odds ratios for AD: 6.5 (95% CI: 2.6 to 16.7) low education/rural residence; 0.5 (95% CI: 0.1 to 2.9) low education/urban residence; 1.5 (95% CI: 0.4 to 5.2) high education/rural residence, comparing with the group of high education/urban residence. CONCLUSION: Childhood rural residence, combined with < or =6 years of school, was associated with an increased risk of AD in this sample. It is possible that low education by itself is not a major risk factor for AD, but, rather, is a marker for other accompanying deleterious socioeconomic or environmental influences in childhood.

Black or African American↗

PubMed2000

Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele.

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.

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PubMed2000

Neuroserpin mutation S52R causes neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy.

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.

Adult↗

PubMed1999

Association of antioxidants with memory in a multiethnic elderly sample using the Third National Health and Nutrition Examination Survey.

Oxidative stress has been implicated both in the aging process and in the pathological changes associated with Alzheimer's disease. Antioxidants, which have been shown to reduce oxidative stress in vitro, may represent a set of potentially modifiable protective factors for poor memory, which is a major component of the dementing disorders. The authors investigated the association between serum antioxidant (vitamins E, C, A, carotenoids, selenium) levels and poor memory performance in an elderly, multiethnic sample of the United States. The sample consisted of 4,809 non-Hispanic White, non-Hispanic Black, and Mexican-American elderly who visited the Mobile Examination Center during the Third National Health and Nutrition Examination Survey, a national cross-sectional survey conducted from 1988 to 1994. Memory is assessed using delayed recall (six points from a story and three words) with poor memory being defined as a combined score less than 4. Decreasing serum levels of vitamin E per unit of cholesterol were consistently associated with increasing levels of poor memory after adjustment for age, education, income, vascular risk factors, and other trace elements and minerals. Serum levels of vitamins A and C, beta-carotene, and selenium were not associated with poor memory performance in this study.

Black or African American↗

PubMed1999

Clinical utility of CERAD neuropsychological battery in elderly Jamaicans.

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.

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PubMed1998

Cognitive decline and education in mild dementia.

Recent studies suggested that education may modify the clinical expression of dementia and Alzheimer's 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 Alzheimer's 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) x 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.

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PubMed1998

Risk factors and Alzheimer's disease: a comparative study of two communities.

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.

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PubMed1997

The dementing disorders.

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.

Activities of Daily Living↗

PubMed1997

The association between Apo E genotype and depressive symptoms in elderly African-American subjects.

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.

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