Biomedical subjects

Walter A Kukull

Publications and source records attributed to Walter A Kukull.

24 records · Page 2Linked to original sources

PubMed2002

Clinical and neuropathological characteristics of hippocampal sclerosis: a community-based study.

BACKGROUND: Hippocampal sclerosis (HS) is a neuropathologic finding characterized by neuronal loss and gliosis in the CA-1 and subiculum of the hippocampus. Previous studies of HS have shown that this is a common postmortem finding in elderly subjects with dementia. However, these studies were from selected samples and therefore are not necessarily representative of patients seen in the general medical community. OBJECTIVES: To examine the clinical and pathologic characteristics of HS in a community-based case series of dementia and to compare these characteristics with those observed in subjects with Alzheimer disease (AD) from the same study sample. METHODS: One hundred thirty-four autopsy cases were available from a community-based registry of dementia. Sixteen cases (12%) had a postmortem diagnosis of HS. Thirty-two comparison control cases with a neuropathologic diagnosis of AD were selected from the same files. Each case of HS was reviewed for HS neuropathologic features, including severity, distribution, and additional pathologic processes. Blinded review of clinical characteristics for the HS and control groups was performed to assess risk factors. RESULTS: There was a wide range of severity and distribution of HS lesions between cases and substantial variability in lesion severity and age within individual cases. Serial neuropsychologic and behavioral assessments revealed similar clinical features and rates of dementia progression between HS and AD groups. Of all neuropsychologic tests performed at enrollment, only enhanced performance on Trails A differentiated the HS from the AD group (64 seconds, 0 errors vs 114 seconds, 0.6 errors; P< or = .05). The number of AD cases with at least 1 apolipoprotein epsilon 4 allele was significantly greater than the HS cases (61% vs 31%; chi(2) = 3.81, P< or = .05). Although medical record review indicated higher frequencies of clinical stroke and neuroradiologic white matter abnormalities in the HS group, risk factors for vascular disease and neuropathologic evidence of cerebrovascular disease did not differ between the groups. CONCLUSIONS: Our results suggest that HS is a frequent pathologic finding in community-based dementia. Individuals with HS have similar initial symptoms and rates of dementia progression to those with AD and therefore are frequently misclassified as having AD. Our clinical and pathologic findings suggest that HS has characteristics of a progressive disorder although the underlying cause remains elusive.

Age of Onset↗

PubMed2002

Dementia epidemiology.

Determining the incidence and prevalence of dementia is an inexact science. Dementia is difficult to define and detect in the population. Even with the difficulties of determining prevalence and incidence, it is clear that dementia causes a substantial burden on our society. Problems with diagnostic inaccuracy and insidious disease onset influence our ability to observe risk factor associations; factors related to survival may be mistaken for risk/protective factors. Current studies suggest that factors influencing brain development or cognitive reserve may delay the onset of AD, perhaps through a protective mechanism or a delay in diagnosis caused by improved performance on cognitive tests. The recent identification of genes that cause dementia suggests that these genes or their biochemical pathways may be involved in the pathogenesis of nonfamilial cases. The contribution of genes that cause disease in and of themselves may be smaller than that of genes that act to metabolize or potentiate environmental exposures. The interaction between gene and environment should be increasingly well studied in the future. Epidemiology must take advantage of these molecular advances. The tasks of public health and epidemiology should still involve prevention, the nonrandom occurrence of disease, and its environmental context in addition to heredity. The tools to address these tasks should continue to be refined.

Aged↗

PubMed2002

Older adults and functional decline: a cross-cultural comparison.

BACKGROUND: The study was conducted to examine the relationships between functional decline, health risk factors, lifestyle practices, and demographic variables in two culturally diverse, community-based samples of White and Japanese American older adults. DESIGN: The study was an analysis of data from two ongoing studies of aging and dementia in King County, Washington. Functional status at baseline was evaluated, and factors associated with functional decline over a 4-year follow-up period were identified. The sample included 1,083 Japanese American and 1,011 White cognitively intact, community-dwelling adults aged 65 and older, who had no functional limitations at baseline and participated in at least one follow-up examination. RESULTS: In 4 years of follow-up, 70% of the subjects reported no increase in functional limitation, and fewer than 5% of subjects declined in five or more activities. Risk factors associated with functional decline included increased age, female gender, medical comorbidity (particularly cerebrovascular disease, arthritis, and hypertension), elevated body mass index, poorer self-perceived health, and smoking. Depression and diabetes were also significant for persons with the greatest functional decline over the 4-year follow-up. Japanese speakers were significantly less likely to decline over the follow-up period than White or English-speaking Japanese American subjects. However, Japanese speakers were more likely to discontinue participation during the follow-up period, and may also have been more likely to underreport symptoms of functional decline. CONCLUSIONS: The present study provides further support that healthy lifestyle practices and prevention of chronic disease are important for maintaining functional independence in older adults. Japanese-speaking subjects were less likely to decline over time, although this could be due in part to differential dropout and reporting bias. These findings have important implications for the design and interpretation of longitudinal studies of older adults. Researchers interested in the effects of ethnicity on health and aging should be cognizant of differences in recruitment and enrollment strategies among studies, and the ways in which these affect study findings. This study also demonstrates the importance of devoting adequate resources to minimize dropouts, and of including measures of health and functioning that are culturally equivalent and less reliant on self-report data.

Aged↗

PubMedDate not supplied

Mitochondrial genetic variants and Alzheimer disease: a case-control study of the T4336C and G5460A variants.

The T4336C mitochondrial genetic variant was associated with Alzheimer disease in several previous studies. Recent investigations, however, failed to confirm this association. We tested this association in newly diagnosed Alzheimer disease cases and controls of similar age and gender recruited from an established HMO serving Seattle, Washington and surrounding areas. In this, the largest case-control study reported to date, the T4336C variant was not associated with Alzheimer disease overall (present in 6 of 236 cases and 7 of 328 controls; odds ratio = 1.20, 95% CI 0.33 to 4.22). There was evidence of effect modification by Apolipoprotein E (APOE) status--among subjects with an APOE epsilon 4 allele, the T4336C variant was associated with disease (present in 5 of 139 cases and none of 82 controls; odds ratio = infinity, 95% CI 0.73 to infinity). APOE may be an important modifier of the T4336C effect, potentially explaining variable findings across previous studies. Alternatively, the positive findings reported to date may simply reflect the problem of "type I" error inherent in genetic association studies. Substantially larger samples than are currently available would be required to resolve this question. G5460(A/T) variants were also investigated and found not to be associated with Alzheimer disease.

Aged↗

PubMedDate not supplied

The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers.

A Clinical Task Force, composed of clinical leaders from Alzheimer's Disease Centers (ADC), was convened by the National Institute on Aging to develop a uniform set of assessment procedures to characterize individuals with mild Alzheimer disease and mild cognitive impairment in comparison with nondemented aging. The resulting Uniform Data Set (UDS) defines a common set of clinical observations to be collected longitudinally on ADC participants in accordance with standard methods. The UDS was implemented at all ADCs on September 1, 2005. Data obtained with the UDS are submitted to the National Alzheimer's Coordinating Center and represent a unique and valuable source of data to support and stimulate collaborative research.

Aged↗

PubMedDate not supplied

The National Alzheimer's Coordinating Center (NACC) Database: an Alzheimer disease database.

The National Alzheimer's Coordinating Center (NACC) is responsible for developing and maintaining a database of patient information collected from the 29 Alzheimer disease centers (ADCs) funded by the National Institute on Aging. Each of the centers collects center-determined data elements on patients enrolled into its center and transmits a minimum dataset to NACC. Data are managed differently at each center depending on that center's research needs. The centers' data systems vary from a single personal computer running spreadsheet software to a network of servers running an advanced data management system such as Oracle. The challenge for NACC is to expand and adjust previously collected data elements into an integrated database that could be used for administrative as well as research purposes. In addition, NACC sought to allow the centers to have the flexibility they needed for data submission. To accomplish this task, NACC designed a database that contained separate specific datasets each with individual data elements. NACC also designed a data management system to easily collect and manage these data. The NACC web site (www.alz.washington.edu) was created to allow access to the data.

Alzheimer Disease↗