Alzheimer Disease: Wichart I

Grünblatt E, Zehetmayer S, Bartl J, Löffler C, Wichart I, Rainer MK, Jungwirth S, Bauer P, Danielczyk W, Tragl KH, Riederer P, Fischer P. · Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria. · J Psychiatr Res. · Pubmed #18603262 No free full text.

Abstract: OBJECTIVES: In ageing population, both Alzheimer's disease (AD) and depression are common. Significant depressive symptoms are often co-morbid with cognitive impairment and dementia. In this study, we attempted to find various factors and markers for both AD and depression in a longitudinal cohort, the Vienna-Transdanube-Aging (VITA)-study. METHODS: The VITA-Study consisted of 305 healthy subjects, 174 subjects with depression only, 55 subjects diagnosed with AD only and 72 subjects with depression as well as AD. Associations between AD and/or depression to gene polymorphisms APO E (epsilon4), choline acetyltransferase (ChAT) 4G to A, serotonin-transporter gene promoter-length, dopamine-D4-receptor, ciliary-neurotrophic-factor-null mutation and brain-derived neurotrophic factor (C270T) and to various known factors were analyzed. RESULTS: AD and depression were significant associated. Significant risk factors found for AD were low education, low folic acid and depressive-symptoms, while for depression were low education and higher nonsteroidal anti-inflammatory drugs (NSAID) consume. Moreover, the ChAT polymorphism associated significant to depression. Gender, education, and ChAT significantly associated with the combination AD and/or depression. CONCLUSION: Such studies must be conducted cautiously, as co-morbidities and gene-environmental-social influences may sway the results dramatically. We found in the VITA-study significant association between depression and AD and between ChAT polymorphism and depression.

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.

Blasko I, Jellinger K, Kemmler G, Krampla W, Jungwirth S, Wichart I, Tragl KH, Fischer P. · Department of Psychiatry, Innsbruck Medical University, Austria. · Neurobiol Aging. · Pubmed #17055615 No free full text.

Abstract: The changes of plasma amyloid beta (Abeta42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimer's disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of Abeta42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine.

Grünblatt E, Schlösser R, Fischer P, Fischer MO, Li J, Koutsilieri E, Wichart I, Sterba N, Rujescu D, Möller HJ, Adamcyk W, Dittrich B, Müller F, Oberegger K, Gatterer G, Jellinger KJ, Mostafaie N, Jungwirth S, Huber K, Tragl KH, Danielczyk W, Riederer P. · Clinic for Psychiatry and Psychotherapy, Department Clinical Neurochemistry, Bayerische Julius-Maximilians-University, Fuchsleinstr 15, Würzburg, Germany. · Neurobiol Aging. · Pubmed #15653171 No free full text.

Abstract: Oxidative stress seems to play an important role in the pathophysiology of Alzheimer's disease (AD). At present there are no easily accessible biochemical markers for AD. We performed activity assays for platelet MAO-B and erythrocyte Cu/Zn-SOD as well as Western blotting for these two proteins. Moreover, we assessed plasma lactoferrin and performed RFLP-analysis for the MAO-B-intron-13-polymorphism in patients from the Vienna-Transdanube Aging (VITA) and from the so called centenarian project. The first one, VITA, is a community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. The centenarian project investigates chronic care in-old patients suffering from AD. In both sexes platelet MAO-B activity increased significantly in the AD group, and Cu/Zn-SOD activity decreased, but the latter effect was significant only in females. No significant difference was found regarding plasma lactoferrin. No correlation was found between MAO-Bi13 and MAO-B platelet activity or allele MAO-Bi13 and disease frequency. These results point to the possibility that a combination of MAO-B and SOD activity levels might be useful tools for an early diagnosis of AD.

Lins H, Wichart I, Bancher C, Wallesch CW, Jellinger KA, Rösler N. · Department of Neurology, Otto-von-Guericke-University, Magdeburg, Germany. · J Neural Transm. · Pubmed #14991454 No free full text.

Abstract: Immunoreactivities of amyloid beta peptide((1-42)) (Abeta42-IR) and total tau protein (TTIR) were measured in lumbar cerebrospinal fluid of 48 patients (12 patients in each group) with normal pressure hydrocephalus (NPH), vascular dementia (VD), Alzheimer's disease (AD), Parkinson's disease without dementia (PD) and 24 controls (CON) using sensitive and specific enzyme immunoassays. TTIR in NPH was not significantly changed compared with VD, PD and CON, while NPH-Abeta42-IR was significantly decreased compared with PD and CON. In AD, significant increases of TTIR and significant decreases of Abeta42-IR were found. Using a TTIR by Abeta42 plot, all NPH, PD, and CON samples were within the non-AD plot region. 92% of AD and VD samples were within the AD and non-AD area, respectively. We conclude that combined measurement of Abeta42-IR and TTIR contributes to the differential diagnosis of NPH vs. AD and of AD vs. VD, respectively.

Rösler N, Wichart I, Jellinger KA. · Ludwig Boltzmann Institute of Clinical Neurobiology, Vienna, Austria. · J Neural Transm. · Pubmed #11314776 No free full text.

Abstract: Immunoreactivities of total apolipoprotein E (ApoE-IR), amyloid beta peptide(1-42) (Abeta42-IR), interleukin-6 (IL-6-IR), substance P (SPIR) and total tau protein (TTIR) were measured in lumbar cerebrospinal fluid samples of patients with Alzheimer's disease (AD), non-Alzheimer's dementias (NAD), neurological disorders without cognitive impairment (OND) and controls without central nervous system disease using sensitive and specific enzyme immunoassay methods. TTIR was highly significantly increased (P < 0,001) and Abeta42-IR was significantly decreased (P < 0,001 vs. OND/CO, P < 0,03 vs. NAD) in the AD cohort compared with the other diagnostic groups. Significant increases in AD were also found for ApoE-IR (P < 0,001) and IL-6 (P < 0,03), but there was a considerable overlap between groups. In the total AD cohort, SPIR was not significantly changed, but AD patients with late disease onset (>65 years) showed significantly higher values than both early onset patients (<65 years) and controls (P < 0,05). Discriminant function analysis showed that Abeta42-IR (cut-off value 375pg/ml) and TTIR (cut-off value 440 pg/ml) levels contributed most to the group classification of patients. At 85% sensitivity for AD and 100% specificity for controls, the combined evaluation of Abeta42-IR and TTIR in this cross-sectional study resulted in a graph separating AD from non-AD patients with increased specificity of 91% and 75% for AD versus OND and NAD, respectively.

Rösler N, Wichart I, Jellinger KA. · Ludwig Boltzmann Institute of Clinical Neurobiology, Vienna, Austria. · Acta Neurol Scand. · Pubmed #11227132 No free full text.

Abstract: OBJECTIVES: In view of contradictory findings in previous studies, to examine the diagnostic value of interleukin-6 measurements in cerebrospinal fluid (CSF) of Alzheimer's disease patients. MATERIAL AND METHODS: Interleukin-6-immunoreactivity (IL-6-IR) was measured in 169 intra vitam lumbar and 21 post mortem ventricular CSF samples of patients with probable and neuropathologically confirmed Alzheimer's disease (AD), non-AD dementias (NAD), neurological disorders without cognitive impairment (OND) and controls (CON) using a specific sandwich enzyme immunoassay. RESULTS: Intra vitam lumbar samples had significantly elevated (P < 0.03) IL-6-IR not only in the AD, but also in the NAD and OND group compared with controls. AD patients with late onset (> 65 years) had slightly (P > 0.05) higher values than patients with early onset (< 65 years). In post mortem ventricular fluid, differences among groups did not reach significance (P > 0.05). CONCLUSION: We conclude that elevations of CSF IL-6-IR can not serve as a diagnostic marker of the disease, but, hypothetically, could reflect presence or activity of IL-6 mediated immunological phenomena in single AD patients.

Rösler N, Wichart I, Jellinger KA. · Ludwig Boltzmann Institute of Clinical Neurobiology, PKH/B Building, Baumgartner Höhe 1, A-1140 Vienna, Austria. · Neurosci Lett. · Pubmed #11166952 No free full text.

Abstract: The concentration of substance P-immunoreactivity (SPIR) in ex vivo lumbar cerebrospinal fluid (CSF) of patients with probable Alzheimer's disease (AD), non-Alzheimer dementias, neurological patients without dementia and control subjects was determined using a sensitive and specific competitive enzyme-immunoassay. There were no significant differences between AD patients and the other groups, but patients with late onset AD (>65 years) showed significantly higher levels of SPIR than patients with early onset (<65 years) and controls. In post mortem ventricular fluid, SPIR levels of all groups were lower compared with the lumbar compartment, but without significant group differences. It is concluded that CSF SPIR may not serve as a diagnostic marker for AD, but possibly could reflect immunological or neuroprotective processes modulated by substance P in late onset AD patients.

Luckhaus C, Spiegler C, Ibach B, Fischer P, Wichart I, Sterba N, Gatterer G, Rainer M, Jungwirth S, Huber K, Tragl KH, Grünblatt E, Riederer P, Sand PG. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #17132983 No free full text.

This publication has no abstract.

Jellinger KA, Rösler N, Wichart I. · No affiliation provided · Ann Neurol. · Pubmed #11761489 No free full text.

This publication has no abstract.