Alzheimer Disease: Fillenbaum GG

Fillenbaum GG. · No affiliation provided · Neurology. · Pubmed #18378880 No free full text.

This publication has no abstract.

Fillenbaum GG, Kuchibhatla MN, Hanlon JT, Artz MB, Pieper CF, Schmader KE, Dysken MW, Gray SL. · Duke University Medical Center and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Durham, NC 27710, USA. · Ann Pharmacother. · Pubmed #16227448 No free full text.

Abstract: BACKGROUND: Since increased oxidative stress may impair cognition and be a risk factor for dementia, there has been interest in determining whether use of antioxidants could protect against such events. OBJECTIVE: To determine whether supplement use of vitamins C and/or E in a community-based sample of older African American and white individuals delayed incident dementia or Alzheimer's disease (AD). METHODS: We selected a subgroup from the Duke Established Populations for Epidemiologic Studies of the Elderly, a longitudinal study of community-representative persons aged 65-105 years living in 5 adjacent counties in North Carolina, and followed them for dementia (1986-1987 through June 2000). Information gathered during in-home interviews included sociodemographic characteristics, health status, health service use, and vitamin use. Diagnosis of dementia and AD was based on evaluations using the clinical and neuropsychological batteries of the Consortium to Establish a Registry for Alzheimer's Disease, with final determination by consensus agreement of specialists using Diagnostic and Statistical Manual of Mental Disorders, third revision, and National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. RESULTS: Of 616 persons initially dementia-free (mean age 73 y; 62% female; 62% African American), 141 developed dementia, of whom 93 developed AD. Increased age and mobility problems were risk factors for dementia (only age for AD), while an increased number of outpatient visits reduced the likelihood of developing dementia. Neither use of any vitamins C and/or E (used by 8% of subjects at baseline) nor high-dose use reduced the time to dementia or AD. CONCLUSIONS: In this community in the southeastern US where vitamin supplement use is low, use of vitamins C and/or E did not delay the incidence of dementia or AD.

Koss E, Peterson B, Fillenbaum GG. · Alzheimer Center, Case Western Reserve University, University Hospitals, Cleveland, Ohio, USA. · Alzheimer Dis Assoc Disord. · Pubmed #10609669 No free full text.

Abstract: The aim of the present study was to identify determinants of attrition in a natural history study of a tertiary care sample of patients with Alzheimer disease (AD) and control subjects. A longitudinal study was performed with 978 patients with AD and 466 control subjects age 50 years and older enrolled at 25 sites of the Consortium to Establish a Registry for Alzheimer's Disease between January 1987 and January 1992; subjects were followed annually for up to 78 months. Both descriptive statistics and polytomous logistic regressions were run to identify determinants of attrition. Of the 1,444 subjects enrolled, 10.5% dropped out after initial evaluation, 31.0% provided at least two waves of data, and 58.4% provided complete follow-up. Inadequate involvement by the site, non-white status, and patient's spouse not enrolled in the study were predictive of dropout; cessation of participation because of death (which may have precluded dropout) predicted continuation in the study. Age, level of education, severity of dementia, and rapidity of progression of disease did not predict dropout. Level-of-site commitment was the most significant determinant of continued participation in this natural history study of AD, followed by white race, and the inclusion of both husband and wife where one is a patient and the other a control subject.

Clark CM, Sheppard L, Fillenbaum GG, Galasko D, Morris JC, Koss E, Mohs R, Heyman A. · Department of Neurology, Alzheimer's Disease Center, University of Pennsylvania, Philadelphia 19104, USA. · Arch Neurol. · Pubmed #10404988 links to  free full text

Abstract: OBJECTIVE: To determine the variability in annual Mini-Mental State Examination scores of patients with Alzheimer disease enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). PATIENTS: A total of 372 patients with probable Alzheimer disease with 1 or more years of follow-up. SETTING: Twenty-one CERAD clinical sites throughout the United States. RESULTS: An average annual decline of 3.4 points in CERAD patients returning for longitudinal reassessments was close to the SD of the measurement error of 2.8 points for the Mini-Mental State Examination. There was wide variability in individual rates of decline. Even with 4 years of follow-up, 15.8% of the patients had no clinically meaningful decline in Mini-Mental State Examination score (defined as a change in initial score >3, ie, 1 SD of measurement error). Validity of measurements of the rate of change in Mini-Mental State Examination scores improved with longer observation intervals and was reliable for most patients when observations were separated by 3 or more years. CONCLUSIONS: Although the Mini-Mental State Examination is a useful screening instrument to assess level of cognitive function, it has limited value in measuring the progression of Alzheimer disease in individual patients for periods less than 3 years because of a large measurement error and substantial variation in change in annual score.

Peterson BL, Fillenbaum GG, Pieper CF, Heyman A. · Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina 27710, USA. · Public Health Nurs. · Pubmed #18816366 No free full text.

Abstract: There is concern that life is curtailed when patients with Alzheimer's disease (AD) are institutionalized. To determine whether placement in a nursing home reduces their remaining years of life, we examined the experience of White patients with AD (n=890) enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Proportional hazards survival analysis using the landmark approach (with the landmark set to 12 months after CERAD entry and reevaluated at succeeding 6-month time intervals through 5 years) indicated that longevity at home and in the nursing home was comparable. Thus, in these patients enrolled at tertiary care medical centers, living at home or in a nursing home did not affect time to death. These data suggest that when home care is no longer feasible, families and nurses counseling them should not feel that they are curtailing life by placing an AD patient in a nursing home.

Fillenbaum GG, van Belle G, Morris JC, Mohs RC, Mirra SS, Davis PC, Tariot PN, Silverman JM, Clark CM, Welsh-Bohmer KA, Heyman A. · Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, USA. · Alzheimers Dement. · Pubmed #18631955 No free full text.

Abstract: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was funded by the National Institute on Aging in 1986 to develop standardized, validated measures for the assessment of Alzheimer's disease (AD). The present report describes the measures that CERAD developed during its first decade and their continued use in their original and translated forms. These measures include clinical, neuropsychological, neuropathologic, and behavioral assessments of AD and also assessment of family history and parkinsonism in AD. An approach to evaluating neuroimages did not meet the standards desired. Further evaluations that could not be completed because of lack of funding (but where some materials are available) include evaluation of very severe AD and of service use and need by patient and caregiver. The information that was developed in the U.S. and abroad permits standardized assessment of AD in clinical practice, facilitates epidemiologic studies, and provides information valuable for individual and public health planning. CERAD materials and data remain available for those wishing to use them.

Purser JL, Fillenbaum GG, Pieper CF, Wallace RB. · Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. · J Am Geriatr Soc. · Pubmed #16274380 No free full text.

Abstract: OBJECTIVES: To apply diagnostic criteria for mild cognitive impairment (MCI) to a geographically representative sample, to estimate the prevalence of MCI, and to estimate 10-year trajectories of incident disability for cognitively intact participants and subgroups with MCI. DESIGN: Prospective cohort; 10 years of follow-up. SETTING: Community-based survey of noninstitutionalized population aged 65 and or older in two rural Iowa counties (Washington and Iowa). PARTICIPANTS: Iowa Established Populations for Epidemiologic Studies of the Elderly (aged > or = 65; N = 3,673; 61.3% female; 99.9% white). MEASUREMENTS: Age, sex, education, Short Portable Mental Status Questionnaire (SPMSQ), 20-item word recall, activities of daily living (ADLs), instrumental activities of daily living (IADLs), chronic medical conditions. RESULTS: MCI was prevalent in 24.7% of participants at baseline. Most participants in the overall cohort remained stable or changed slowly (< or = 1 new limitations) over 10 years (63.1% for SPMSQ, 89.3% for word recall, and 61.7% for ADL disability). For MCI/no prevalent IADL disability (Stage 1 MCI), disability progression was similar to that in the cognitively intact subgroup (median = 0.08 vs 0.05 disabilities per year). For MCI plus prevalent IADL disability (Stage 2 MCI), the median rate of change was equivalent to that of the severely impaired (0.23 disabilities per year; interquartile range = 0.12-0.36). CONCLUSION: Unlike participants with MCI who reported no IADL limitations, those with such limitations were more likely to develop ADL disability--a prerequisite for a diagnosis of dementia.

Fillenbaum GG, McCurry SM, Kuchibhatla M, Masaki KH, Borenstein AR, Foley DJ, Heyman A, Larson EB, White L. · Center for the Study of Aging and Human Development, Box 3003, Duke University Medical Center, Durham, NC 27710, USA. · J Int Neuropsychol Soc. · Pubmed #15966108 No free full text.

Abstract: Norms for cognitive measures used to assess dementia are scant for minority groups, in particular for older Japanese Americans. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we compared the baseline performance of demented and nondemented Japanese Americans. Participants came from two harmonized epidemiological studies of dementia which were examined separately: the Kame Project, Seattle (350 men and women; 201 nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418 men; 120 nondemented), age 71 and older. The measures examined were Verbal Fluency; abbreviated Boston Naming; constructional praxis; and Word List Learning, Recall, and Recognition. Within each study, the CERAD measures distinguished between nondemented participants and those with mild cognitive impairment. Among persons with dementia, average level of performance decreased as severity of dementia increased. Determinants of score (age, education, language of administration, stage of dementia) varied between the two studies. Among Japanese Americans, the CERAD Neuropsychology Battery distinguished nondemented persons from those with dementia, but was less consistent in distinguishing levels of severity of dementia. This battery is useful for comparative epidemiological studies of dementia in minority populations.

Blazer DG, Fillenbaum GG, Gold DT, Burchett BM, Hays JC. · Department of Psychiatry and Behavioral Sciences, Center for the STudy of AGing and Human Development, Duke University Medical Center, Durham, NC, USA. · J Aging Health. · Pubmed #14594022 No free full text.

Abstract: The epsilon4 allele of apolipoprotein E (APOE) has been associated with health-related outcomes that may adversely affect quality of life (QOL) in older adults. In the absence of published information, we sought to determine whether the epsilon4 allele was associated with subjective QOL across 5 parameters in a community sample of older adults. Design: Prospective cohort study. Setting: Community-based sample of older adults in North Carolina (Duke site of the Established Populations for Epidemiologic Studies of the Elderly [Duke EPESE]). Participants: Self-responding genotyped sample members (n = 1,880) of whom 1,254 provided longitudinal data. Measurements: APOE genotype and five newly constructed, reliable, and valid measures of subjective QOL derived from the Duke EPESE questionnaire. The 5 parameters measured were social, economic, mental and physical health, and functional status. Control variables included age, gender, race (African American or White), education and urban/rural residence. Results: Among those with good baseline QOL, there was no significant association between the epsilon4 allele and any of the parameters of subjective QOL in longitudinal analyses. In controlled longitudinal analysis, older age women predicted poorer functional status; being African American, and reporting lower education predicted poorer subjective economic well-being; and being African American predicted better self-assessed mental health. Conclusions: This study is among the first to explore the association of the epsilon4 allele with overall QOL. Considered from a public health perspective, these findings challenge the uncritical assumption that the presence of this susceptibility gene in the population implies an excess burden of poor QOL. The findings do not contradict the previous association of epsilon4 with Alzheimer's disease (AD) and other conditions. Such conditions continue to merit full attention.

Taylor DH, Fillenbaum GG, Ezell ME. · Center for Health Policy, Law and Management, Terry Sanford Institute of Public Policy, Duke University, 122 Old Chemistry Building, Box 90253, Durham, NC 27708, USA. · J Clin Epidemiol. · Pubmed #12393082 No free full text.

Abstract: We linked Medicare claims data to information on 417 patients with a clinical diagnosis of Alzheimer's disease in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) to determine what proportion of them were identified as having Alzheimer's disease (AD) in Medicare claims records. Seventy-nine percent of these patients were identified as having AD using 5 years of claims data; 87% were identified as demented when a broader set of ICD-9-CM codes was used. An Anderson-Gill counting process approach was used to model the "hazard" of patients being identified as having AD in Medicare claims data. CERAD patients with mild dementia were less likely to be identified in the claims data as having AD. Once identified in Medicare claims as having AD, patients were more likely to be so identified again. When using only the physician supplier and institutional outpatient files, approximately 75% of CERAD patients were identified as having AD; hospital files used alone identified less than one-third (29%) of the CERAD patients as having AD. The data indicate that at least 3 consecutive years of physician supplier and physician outpatient claim files should be used to identify Medicare beneficiaries with AD using Medicare claims.

Trapp-Moen B, Tyrey M, Cook G, Heyman A, Fillenbaum GG. · School of Nursing, Duke University, Durham, NC 27710, USA. · Gerontologist. · Pubmed #11405439 No free full text.

Abstract: PURPOSE OF STUDY: To maximize respondent participation in a study of the prevalence, incidence, and natural history of dementia. DESIGN AND METHODS: Clinical research nurses were trained to carry out evaluations for dementia in the home. We describe the assessment and training procedures used and note the advantages and drawbacks of this approach. RESULTS: Nurse identification of the presence of dementia agreed well with that of medical specialists (kappa = 0.84), but was slightly poorer regarding type of dementia (kappa = 0.71). IMPLICATIONS: Use of nurses for such activity need not be limited to epidemiological studies, but is relevant also in clinical practice.

Fillenbaum GG, Heyman A, Huber MS, Ganguli M, Unverzagt FW. · Center for the Study of Aging and Human Development, Duke University, Medical Center, Durham, North Carolina 27710, USA. · J Int Neuropsychol Soc. · Pubmed #11396552 No free full text.

Abstract: 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.

Fillenbaum GG, Hanlon JT, Landerman LR, Schmader KE. · Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC 27710, USA. · Am J Epidemiol. · Pubmed #11159158 links to  free full text

Abstract: The authors investigated whether postmenopausal estrogen use helps to maintain cognitive function; a brief screen, the Short Portable Mental Status Questionnaire (SPMSQ), was used. Information was gathered from a stratified, random sample of 1,907 African-American and White women (aged 65-100 years) participating in the longitudinal Duke Established Populations for Epidemiologic Studies of the Elderly project carried out in five urban and rural counties of North Carolina. All women were cognitively unimpaired in 1986-1987 and were evaluated 3 and 6 years later. Decline in cognitive function was measured as an increase of two or more errors on the SPMSQ and crossing of an SPMSQ threshold indicative of cognitive impairment. Recency and continuity of estrogen use were measured. Univariate analyses indicated that recent (crude odds ratio = 0.42, 95% confidence interval: 0.21, 0.86) and continuous (crude odds ratio = 0.32, 95% confidence interval: 0.13, 0.81) estrogen use reduced the risk of cognitive decline but not of cognitive impairment. After adjustment for demographic and health characteristics, protective effects became nonsignificant. While postmenopausal use of estrogen may be protective for Alzheimer's disease, current findings based on a brief cognitive screen suggest that it is not protective for cognitive decline related to aging.

Heyman A, Fillenbaum GG, Gearing M, Mirra SS, Welsh-Bohmer KA, Peterson B, Pieper C. · Division of Neurology, Duke University, Durham, NC, USA. · Neurology. · Pubmed #10371532 No free full text.

Abstract: OBJECTIVE: To compare the clinical, neuropsychological, and neuropathologic findings in patients with AD alone with those in patients with the Lewy body variant of AD (LBV). BACKGROUND: Prior studies indicate that patients with LBV not only have distinct clinical and neuropsychological differences from those with AD alone, but have a poorer prognosis with shorter survival time. METHODS: The authors evaluated 74 patients with autopsy-confirmed AD alone and 27 patients with LBV, and compared demographic characteristics and clinical, neuropsychological, and neuropathologic findings. RESULTS: The two groups of patients were equivalent with respect to age at time of entry into the study, years of education, and sex. Two or more extrapyramidal clinical manifestations were found in 44% of patients with LBV, compared with 16% of patients with AD alone (p = 0.02). Duration of survival after entry into the study was similar in both groups, with a mean survival of 3.6 (+/-2.1) years for AD alone versus 3.8 (+/-1.9) years for LBV. Of the various neuropsychological tests administered at the last Consortium to Establish a Registry for Alzheimer's Disease evaluation, only delayed recall of a learned word list was significantly different in the two groups, with 32% of patients with LBV versus 15% of patients with AD alone recalling any items (p = 0.04). Neuropathologic findings confirmed those of previous studies and showed that neurofibrillary tangles were significantly less frequent in the neocortex of patients with LBV than in those with AD alone. CONCLUSION: Compared with patients with AD alone, those with LBV had a greater frequency of extrapyramidal manifestations, somewhat better recall on a selected memory task at their final evaluation, and a significantly lower frequency of neocortical neurofibrillary tangles at autopsy. There were no differences between the two groups, however, in survival time from entry into the study.