Alzheimer Disease: Weissgram S

Jungwirth S, Zehetmayer S, Bauer P, Weissgram S, Tragl KH, Fischer P. · Ludwig Boltzmann Institute of Aging Research, Vienna, Austria. · Int Psychogeriatr. · Pubmed #19327204 No free full text.

Abstract: BACKGROUND: To date, no single instrument has proved to be adequate for screening for Alzheimer's dementia (AD). The aim of this study was to identify a combination of instruments which were highly sensitive for screening late onset AD. METHODS: Subjects were drawn from the Vienna TransDanube Aging (VITA) study. This is an interdisciplinary, longitudinal community-based cohort study of the 21st and 22nd district of Vienna (Austria). Data refer to the cohort of 478 individuals at age 78 who took part in the first follow-up investigation of the VITA study. The psychometric instruments which were investigated were: the Ten-Point Clock Test, the Human-Figure Drawing Test, a Delayed Selective Reminding Test, Naming, the Trail Making Test-B, and Verbal Fluency. Further instruments were the Pocket Smell Test, and Subjective Memory Complaints. Data were analyzed using logistic regression analyses and cross validation. RESULTS: A combination of the Delayed Selective Reminding Test and Verbal Fluency was best for screening AD (R2 = 0.38, main model). An area under the ROC curve of 0.829 was reached. This model discriminated between subjects with incident AD and subjects who did not have incident AD with a sensitivity of 91% and a specificity of 56%. CONCLUSION: The combination of an episodic memory test and a test of verbal fluency was an effective way of screening for AD.

Fischer P, Zehetmayer S, Jungwirth S, Weissgram S, Krampla W, Hinterberger M, Torma S, Rainer M, Huber K, Hoenigschnabl S, Gelpi E, Bauer K, Leitha T, Bauer P, Tragl KH. · Ludwig Boltzmann Institute of Aging Research, Vienna, Austria. · Dement Geriatr Cogn Disord. · Pubmed #18446027 No free full text.

Abstract: BACKGROUND: Few prospective community-based cohort studies have so far concentrated specifically on the risk factors for Alzheimer dementia (AD) with onset after the age of 75 years. METHODS: We prospectively investigated a birth cohort of 585 nondemented inhabitants in the area on the East bank of the river Danube who were born between 1925 and 1926. They were investigated at the age of 75 years and followed up after 30 months. The follow-up was possible with 488 probands; 36 died, and 61 refused to participate. RESULTS: In multivariate analysis an elevated risk for late-onset AD could be found for (1) history of depressive episodes (OR = 2.09; 95% CI = 1.25-3.48); (2) the epsilon 4 allele of the APOE gene (OR = 1.86; 95% CI = 1.08-3.23); (3) lower serum level of folate (OR = 0.92; 95% CI = 0.87-0.98); (4) no chronic use of nonsteroidal anti-inflammatory drugs (OR = 0.40; 95% CI = 0.20-0.81), and (5) lower education (OR = 1.43; 95% CI = 1.03-2.00). CONCLUSIONS: Five risk factors for late-onset AD could be confirmed, which might be targets for preventive strategies.

Blasko I, Jungwirth S, Jellinger K, Kemmler G, Krampla W, Weissgram S, Wichart I, Tragl KH, Hinterhuber H, Fischer P. · Department of Psychiatry, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. · J Psychiatr Res. · Pubmed #18155247 No free full text.

Abstract: In the course of cognitive deterioration leading to Alzheimer's disease (AD) the increase of amyloid beta (Abeta42) in cerebrospinal fluid or plasma might be an initial event. We previously reported about the associations between concomitant medication and plasma Abeta42 levels in the non-demented population cohort of the Vienna transdanube aging study at baseline. In the present study, the longitudinal influence of insulin, gingko biloba, non-steroidal anti-inflammatory drugs (NSAIDs), oral anti-diabetics (sulfonylurea and biguanides), estrogens, fibrates, and statins on plasma Abeta42 are presented. Associated with medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42. Long-term users of gingko biloba, independent of their MTA, had significantly decreased plasma Abeta42 and the age-dependent increase of plasma Abeta42 was significantly smaller in long-term gingko biloba treated subjects. The use of fibrates also decreased plasma Abeta42 levels. In multiple testing considering interactions between medications, gender, APOE-epsilon4 presence and creatinine, insulin long-term users again showed significantly increased levels; fibrate and gingko biloba users showed a trend to rather decreased plasma Abeta42 levels compared to the non-users (p=0.05-0.08). Neither statins nor NSAIDs showed a significant effect on plasma Abeta42 in this model. Measuring the effect on cognition, no single medication studied was a significant predictor of conversion to AD or mild cognitive impairment (MCI). Whether the use of gingko biloba might prevent the conversion to MCI or AD needs to be proven in prospective, clinical trials.

Fischer P, Jungwirth S, Zehetmayer S, Weissgram S, Hoenigschnabl S, Gelpi E, Krampla W, Tragl KH. · Ludwig Boltzmann Institute of Aging Research, Medical University Vienna, Vienna, Austria. · Neurology. · Pubmed #17242334 No free full text.

Abstract: OBJECTIVE: To compare the rates of conversion to Alzheimer dementia (AD) between subtypes of mild cognitive impairment (MCI) in a community-based birth cohort investigated at age 75 and followed up after 30 months. METHODS: The Vienna Trans-Danube Aging Study investigated every inhabitant of the area on the left shore of the river Danube who was born between May 1925 and June 1926. With use of the official voting registry, 1505 subjects were contacted and 697 participated. Data refer to the cohort of 581 nondemented individuals who completed extensive neuropsychological examination at baseline. Follow-up after 30 months was possible in 476 probands (35 deceased). RESULTS: The 141 patients with MCI at baseline were classified into two subtypes. At follow-up, 41 of these patients with MCI were diagnosed with AD. Conversion rates to AD were 48.7% (CI: 32.4 to 65.2) for amnestic MCI and 26.8% (CI: 17.6 to 37.8) for nonamnestic MCI. Another 49 AD cases originated from cognitive health at baseline (12.6%; CI: 9.4 to 16.3). CONCLUSIONS: Patients with mild cognitive impairment (MCI) showed a high probability to be diagnosed with Alzheimer dementia (AD) after 30 months. Subtypes of MCI were not useful in defining early stages of various types of dementia: Not only amnestic MCI but also nonamnestic MCI converted frequently to AD, and conversion to vascular dementia and dementia with Lewy bodies was not restricted to nonamnestic MCI.

Jungwirth S, Weissgram S, Zehetmayer S, Tragl KH, Fischer P. · Ludwig Boltzmann Institute of Aging Research, Vienna, Austria. · Int J Geriatr Psychiatry. · Pubmed #15852463 No free full text.

Abstract: BACKGROUND: Mild cognitive impairment (MCI) is defined to diagnose prodromal dementia and prodromal Alzheimer dementia, in particular. OBJECTIVE: The main aim of this study is to identify subtypes of MCI in comparison to the frequency of Petersen's MCI-amnestic in an elderly age-cohort. PARTICIPANTS: The study is based on the cross sectional data from the Vienna-Transdanube-Aging (VITA) study. The data refer to the age cohort of 592 individuals at age 75 to 76 years who completed extensive neuropsychological examination. RESULTS: Dementia was present in 15 subjects (2.5%, CI: 1.4-4.1). 141 subjects (23.8%, CI: 20.4-27.5) of the entire age cohort 75 (n = 592) showed cognitive impairment without dementia concerning one or more cognitive functions (1.5 SD paradigm). These subjects were assigned to three subtypes of MCI: Selective Memory Impairment: n = 22 (3.7%, CI: 2.3-5.6), Memory Impairment+Non-Memory Impairment: n = 31 (5.2%, CI: 3.6-7.4) and Non-Memory Impairment: n = 88 (14.9%, CI: 12.1-18.0). CONCLUSIONS: The frequency of MCI-amnestic, the so-called prestage of AD according to Petersen, was very low (0.5%, CI: 0.1-1.5) compared to the estimated incidence rates of AD at this age. Established criteria of MCI could be modified in order to include a higher percentage of high-risk subjects for later developing Alzheimer dementia.

Mostafaie N, Rossmanith W, Hombauer H, Dechat T, Raffelsberger T, Bauer K, Worofka B, Kittl E, Hofmann J, Hejtman M, Kirchmeyr W, Schreiber W, Weissgram S, Jungwirth S, Fischer P, Bittner R, Huber K. · L. Boltzmann Institute of Aging Research, Ludwig Boltzmann Society, Donauspital, Austria. · J Neural Transm. · Pubmed #15338331 No free full text.

Abstract: The Vienna Transdanube Aging (VITA) study searches for early markers of Alzheimer's disease (AD) by examining the mental status in a community-based cohort of 606, 75-years old volunteers that are then related to various clinical and genetic analyses. To determine whether mutations in mtDNA are involved in expression of AD, the mtDNA of 79 "control" participants is screened for alterations by sequencing of "hot-spot-regions". This study on mtDNA mutations has eliminated the influence of aging on the occurrence of mtDNA alterations by sequencing samples from persons at the age of exactly 75 years. Thus, our cohort reveals a snap-shot of mitochondrial sequences of elderly persons.So far, a high percentage (56%) of persons with known or unknown mutations in the fragments analyzed were found. These data will be compared in due time to a cohort of participants with proven late-onset AD.

Jungwirth S, Fischer P, Weissgram S, Kirchmeyr W, Bauer P, Tragl KH. · Ludwig Boltzmann Institute for Aging Research, Vienna, Austria. · J Am Geriatr Soc. · Pubmed #14728638 No free full text.

Abstract: OBJECTIVES: To help answer the question of whether subjective memory complaints are a useful feature in classification systems addressing early stages of Alzheimer's disease. DESIGN: A cross-sectional investigation in the context of a community-based cohort study. SETTING: Vienna, Transdanube-a geographically defined, urban, working-class area. PARTICIPANTS: Three hundred two nondemented 75-year-olds were examined with regard to subjective memory complaints and objective memory performance. The patients were divided into two groups with respect to subjective memory complaints and into two groups with respect to memory performance on the Fuld Object Memory Evaluation. MEASUREMENTS: The percentage of individuals with memory complaints who also had objective memory impairment and the percentage of individuals with objective memory impairment who also complained about their memory were measured. RESULTS: One-tenth (10.6%) (95% confidence interval (CI)=7.7-14.7) of community based sample of 75-year-old subjects complained about their memory. There was no difference between complainers and noncomplainers with regard to actual memory performance. Only 6.3% (95% CI=0.16-30.2) of memory-impaired subjects complained about their proven memory impairment. CONCLUSION: About 94% (95% CI=69.8-99.8) of memory-impaired individuals do not complain about memory problems. Subjective memory complaints may not be a useful feature in current diagnostic criteria of mild cognitive impairment.

Fischer P, Jungwirth S, Krampla W, Weissgram S, Kirchmeyr W, Schreiber W, Huber K, Rainer M, Bauer P, Tragl KH. · Ludwig Boltzmann Institute for Aging Research, Vienna, Austria. · J Neural Transm Suppl. · Pubmed #12456056 No free full text.

Abstract: The Vienna Transdanube Aging study "VITA" is a prospective, interdisciplinary cohort-study of all 75-years old inhabitants of the 21. and 22. district of Vienna (n = 1,745), which started in May 2000. The study design is described in this paper for the first time. The main scientific question of the study concerns the prediction of incident dementia in the elderly. The main statistical analysis will compare 8 predictors: episodic memory, verbal fluency, subjective memory complaints, depression, APOE-epsilon4, MAO-B activity in thrombocytes, MRT hippocampal atrophy, and MRT atrophy of the substantia innominata. The whole investigation comprises medical and psychosocial interviews, psychological tests, psychiatric and neurological scales, blood characteristic, genetic factors and cranial magnetic resonance imaging. Various variables will be compared with each other concerning sensitivity and specificity of prediction of cognitive decline. The dependent variable of the intended statistical analysis will be the individual's difference between Mini Mental State Examination scores at the two times of investigation. A high level of participation in geriatric epidemiological studies increases the general applicability of results but recruitment procedures must not ignore the individual's right to privacy and integrity. Using a liberal recruitment procedure as recommended by the local ethics commission the level of participation is between 36.7% and 44.3%.