Alzheimer Disease: Kemmler G

Weiss EM, Kohler CG, Vonbank J, Stadelmann E, Kemmler G, Hinterhuber H, Marksteiner J. · Department of General Psychiatry, Innsbruck Medical University, Innsbruck, Austria. · Am J Geriatr Psychiatry. · Pubmed #19038896 No free full text.

Abstract: OBJECTIVE: To investigate emotion discrimination abilities in healthy comparison subjects, patients with mild cognitive impairment (MCI), early and moderate Alzheimer disease (AD). DESIGN: Prospective study design. SETTING: Outpatient memory clinic, Department of Psychiatry, Innsbruck, Austria. METHODS: One hundred forty-one subjects older than 60 years were included in the study. Thirty-five subjects were classified as healthy comparison subjects, 51 subjects as MCI (21 subjects with amnestic MCI single domain, 31 subjects with amnestic MCI multiple domain), 32 subjects with early AD and 23 subjects with moderate AD. MEASUREMENTS: All subjects were tested on an extensive neuropsychological test battery including the Penn Emotion Recognition Tests and depression symptoms were assessed additionally. RESULTS: Healthy subjects and patients with MCI, early and moderate AD differed significantly in the recognition of all emotions and neutral faces combined. When separated by emotion, the authors found significant differences in emotion recognition between the diagnostic groups for happy, sad, fearful, and neutral faces. Compared with comparison subjects, amnestic MCI patients single domain did not differ significantly in their emotion recognition abilities, but amnestic MCI multiple domain patients were already impaired in the recognition of overall emotions, sad, fearful, and neutral faces and the deficits increased with the severity of AD. Depression had a significant influence on the recognition of overall emotion and neutral faces and increased the probability of misinterpreting neutral faces as sad leading to a negative bias. CONCLUSIONS: Diminished abilities for emotion discrimination are already present in patients with MCI and further decreased with AD progression.

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.

Blasko I, Knaus G, Weiss E, Kemmler G, Winkler C, Falkensammer G, Griesmacher A, Würzner R, Marksteiner J, Fuchs D. · Department of Psychiatry, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Tyrol, Austria. · J Psychiatr Res. · Pubmed #16542679 No free full text.

Abstract: The pro-inflammatory reaction of the immune system is a feature of healthy aging and might influence the progression of Alzheimer's disease (AD). Neopterin is a pteridine derivative, released from macrophages upon stimulation with pro-inflammatory cytokine interferon-gamma. Forty-three probable AD patients were investigated at baseline and follow up (14.5+/-0.5 months; mean+/-s.e.m.). We assessed the clinical progression by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery and compared cognitive changes to serum concentrations of neopterin, C-reactive protein (CRP) and antibody to cytomegalovirus (CMV). The mean neopterin concentrations increased significantly from 9.8+/-1.0 to 13.6+/-2.1 nM (p=0.04). In contrast, mean CRP concentrations at baseline was 0.46+/-0.1 and non-significantly decreased to 0.28+/-0.04 mg/dl. Of AD patients 70% were CMV IgG-seropositive at baseline and CMV-antibody concentrations correlated with levels of neopterin (Spearman r=0.386, p=0.016). CERAD scores did not correlate with any of immune parameters at baseline. At follow up, the increase of neopterin correlated significantly with the decrease in the total CERAD and MMSE scores, according to the clinical progression (r=-0.353, p<0.05 and r=-0.401, p<0.01, respectively). Subdividing the sample with respect to baseline MMSE scores, neopterin concentrations significantly increased only in the group of MMSE<20. In the multiple testing covariated for age, gender, Apolipoprotein E-epsilon4 allele, time difference between both measurements, neopterin remained significantly associated with cognitive decline. In summary, neopterin concentrations correlated with cognitive decline in AD patients, which might be due to high CMV seropositivity in that population.

Blasko I, Lederer W, Oberbauer H, Walch T, Kemmler G, Hinterhuber H, Marksteiner J, Humpel C. · Department of Psychiatry, Innsbruck Medical University, Innsbruck, Austria. · Dement Geriatr Cogn Disord. · Pubmed #16244482 No free full text.

Abstract: Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer's disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using beta-amyloid 1-42 (Abeta42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/Abeta42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-alpha, TGF-beta1, MIP-1alpha) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/Abeta42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/Abeta42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age.

Weiss U, Bacher R, Vonbank H, Kemmler G, Lingg A, Marksteiner J. · Department of Psychiatry, University of Innsbruck, Austria. · J Clin Psychiatry. · Pubmed #12716263 No free full text.

Abstract: BACKGROUND: In vivo proton magnetic resonance spectroscopy is a safe and noninvasive tool that can be used to study aspects of brain chemistry and metabolism. This study was designed to evaluate its role in routine application to reveal the diagnostic reasons for cognitive impairment. METHOD: 37 Alzheimer's disease patients (NINCDS-ADRDA criteria), 31 patients with subcortical ischemic vascular dementia (Chui et al. criteria), and 13 subjects with subjective cognitive impairment (DSM-IV criteria) were included in this retrospective study. Magnetic resonance images were used for atrophy rating; additionally, proton magnetic resonance spectroscopy was performed. RESULTS: Significantly reduced N-acetylaspartate levels (p <.05) were found in both patients with Alzheimer's disease and patients with subcortical ischemic vascular dementia compared to the group with subjective memory complaints. The ratios of N-acetylaspartate/creatine and N-acetylaspartate/myo-inositol were significantly lower in Alzheimer's disease patients compared to patients with vascular dementia (p =.012) or patients with subjective memory impairment (p =.002). N-acetylaspartate/creatine and N-acetylaspartate/myo-inositol ratios were positively correlated to the degree of cerebral atrophy. Disoriented patients displayed a low N-acetylaspartate/creatine ratio. In contrast, we were not able to relate concurrent psychotic or behavioral symptoms to any spectroscopic parameter. CONCLUSION: This study indicates that proton magnetic resonance spectroscopy parameters could provide additional information in differentiating between Alzheimer's disease, subcortical ischemic vascular dementia, and subjective cognitive impairment. Therefore, this method can contribute to the routine diagnosis of dementia. Psychiatric and behavioral symptoms associated with dementia or due to a major psychiatric disorder cannot be related to changes in the measured proton magnetic resonance spectroscopy parameters.

Gurka P, Bacher R, Kohl C, Kemmler G, DeCol C, Weiss E, Bodner T, Hinterhuber H, Lingg A, Marksteiner J. · Department of Psychiatry, Anichstrasse 35, A-2060 Innsbruck, Austria. · Int J Geriatr Psychiatry. · Pubmed #11921159 No free full text.

This publication has no abstract.