Alzheimer Disease: Hinterhuber H

Kerer M, Marksteiner J, Hinterhuber H, Mazzola G, Steinberg R, Weiss EM. · Abteilung für Allgemeine Psychiatrie, Medizinische Universität Innsbruck. · Neuropsychiatr. · Pubmed #19272287 No free full text.

Abstract: Patients suffering from dementia are nevertheless still able to render exceptional musical performances. For example, they can recognize music from childhood and reproduce lyrics and melodies of songs with four verses. Furthermore, behavioural symptoms such as psycho- motor agitation and crying, but also aggressive behaviour can be positively influenced by music and motivation and positive emotions can be increased. A variety of physiological and psychological changes occur when patients are listening to music. Previous research could show that music activated different parts of the brain especially in the temporal cortex, but also motoric areas in the frontal cortex, thalamus and cerebellum were essential for rhythm, melody and harmony perception and processing. Music therapy is an interpersonal process in which music is used within a therapeutic relationship to address physical, emotional, cognitive, and social needs of individuals with various psychiatric or medical conditions. However, until now only little research has been directed towards non-pharmacological treatments like music therapy in dementia patients. Further research is warranted to investigate the long term influence of music therapy on patients suffering from dementia.

Marksteiner J, Hinterhuber H, Humpel C. · Department of General Psychiatry, Innsbruck Medical University, Innsbruck, Austria. · Drugs Today (Barc). · Pubmed #17612711 No free full text.

Abstract: Alzheimer's disease is a chronic progressive neurodegenerative disease and it is the most prevalent type of dementia. Diagnostic means, including neuroimaging methods, are continuously improving. Nevertheless, it is still a challenge to increase the sensitivity and specificity of a diagnosis of Alzheimer's disease. Two diagnostic areas are especially challenging: first, differentiating early stages of Alzheimer's disease from mild cognitive impairment and normal aging; and second, increasing diagnostic specificity especially when similar clinical symptoms are shared by various types of dementia. To date, the analysis of beta-amyloid(1-42), total tau and phospho-tau-181 from cerebrospinal fluid (CSF) are the best biological markers to diagnose Alzheimer's disease and differentiate it from other forms of dementia with a high reliability and validity. This article reviews the use of CSF biomarkers and of putative blood-related markers.

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.

Marksteiner J, Pirchl M, Ullrich C, Oberbauer H, Blasko I, Lederer W, Hinterhuber H, Humpel C. · Department of General Psychiatry, Innsbruck Medical University, Innsbruck, Austria. · Pharmacology. · Pubmed #18810245 No free full text.

Abstract: Alzheimer's disease (AD) is a severe, progressive and chronic disorder with strong cognitive deficits. Diagnosis of probable AD can be performed by measuring biomarkers in cerebrospinal fluid (CSF). The aim of the present study was to measure CSF levels of nerve growth factor (NGF), the anti-NGF auto-antibody, and the cholinesterases AChE and BChE, and to correlate them with beta-amyloid, tau and phospho-tau-181. We could show that NGF-like immunoreactivity, but not anti-NGF auto-antibody, was significantly enhanced in AD patients compared to healthy subjects, while both cholinesterases were not changed. beta-Amyloid(1-42) was decreased, while tau and phospho-tau-181 were increased. The commercial Promega NGF ELISA detected mature NGF but not wild-type-human-pro-NGF. Using a bioassay of brain slices, we showed that recombinant mature NGF enhanced survival of cholinergic neurons, while wild-type human pro-NGF displayed a less pronounced effect. The addition of CSF to brain slices exhibited strong toxic effects on the survival of cholinergic neurons. We conclude that in CSF of AD patients (at least partly) mature NGF-like immunoreactivity is enhanced, and is masked in a bioassay by the toxic properties of CSF.

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, 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.

Blasko I, Bodner T, Knaus G, Walch T, Monsch A, Hinterhuber H, Marksteiner J. · Department of Psychiatry, University Hospital of Innsbruck, Austria. · Pharmacology. · Pubmed #15292648 No free full text.

Abstract: In a pilot study designed as a case control study the efficacy of donepezil treatment was investigated in patients with Alzheimer's disease (AD). Patients were stratified according to radiological criteria into patients without (AD group) and with subcortical vascular lesions (AD+SVD group). Changes in cognition were assessed as the primary outcome measurement after 6 and 18 months of treatment by the Mini-Mental Status Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery. After 6 months, patients had improved from baseline by 0.7 points in MMSE score in the AD group and by 1.8 in the AD+SVD group. After 18 months of treatment, the AD+SVD group performed significantly worse in one CERAD subscore, whereas a deterioration in two subscores was observed in the AD group. A comparison between the 2 groups revealed that treatment did not lead to statistically significant differences between the AD and AD+SVD groups in any of CERAD parameters following 6 or 18 months of treatment. These data support previous observations that donepezil therapy is effective in AD patients with and without subcortical vascular lesions.

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.

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