Alzheimer Disease: Rainer M

Schmidt R, Neff F, Lampl C, Benke T, Anditsch M, Bancher C, Dal-Bianco P, Reisecker F, Marksteiner J, Rainer M, Kapeller P, Dodel R. · Universitätsklinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #18826870 No free full text.

Abstract: Cholinesterase inhibitors and memantine can slow the course of Alzheimer's disease. In Austria the frequency of treatment is in the upper third among countries of the EU. Yet, the majority of Alzheimer patients does not receive adequate medication. Compliance to treatment is low. Studies on cholinesterase inhibitors show that only one third and one fifth of patients adhere to medication after 3 months and 12 months, respectively. Causes for low compliance are only partly patient-related, many factors are system-inherent. Knowledge of these factors is a pre-requisite for the treating physician to improve current unfavourable situation. Present treatment strategies are symptomatic, causal disease-modifying therapies are urgently needed. Research activity in the field is high and dominated by the amyloid hypothesis. We here review the basis and recent studies on secretase-inhibitors, immunization, aggregation of Abeta, statins and PPARgamma-agonists. Research towards strategies against tau-pathology is less dominant and focuses on inhibition of kinases and increase of activity of phosphatases. Causal therapies would have great effects on a population basis even if efficacy is only moderate. A disease-modifying therapy which delays the onset of Alzheimer disease by 5 years, will probably reduce the number of patients by nearly 50% during the next 50 years.

Schmidt R, Alf C, Bancher C, Benke T, Berek K, Dal-Bianco P, Führwürth G, Imarhiagbe D, Jagsch C, Lechner A, Rainer M, Reisecker F, Rotaru J, Uranüs M, Walter A, Winkler A, Wuschitz A. · Universitätsklinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #19272293 No free full text.

Abstract: We performed a 6-month open-label study on the use of the transdermal rivastigmine patch in clinical routine in 103 patients with Alzheimer's disease from 25 outpatient services in Austria. After baseline, safety and tolerability of the 10 cm2--rivastigmine patch was assessed at week 4, 12 and 24 in all patients. A Mini Mental State Examination was done at baseline and at week 12 and 24. Skin adherence of the patch was very good or good in 85% of study participants. Only 2.9% of patients had gastrointestinal adverse events. Local skin reactions occurred in 23% of individuals. Skin alteration were mostly mild in severity. In only 6.8% of subjects did they result in termination of treatment. At the earliest skin reactions were observed after 3 months of treatment. Cognitive functioning of patients improved comparable to the controlled trial which led to approval of the rivastigmine patch. In daily routine the safety profile of the rivastigmine patch is favourable, as is the response to treatment. Local, mostly mild skin reactions affect approximately every fifth patient, and they occur relatively late in the course of therapy. Patients and their caregivers should receive detailed information about skin reactions to omit unnecessary drop outs to treatment.

Muresanu DF, Rainer M, Moessler H. · Neurology Department, University of Cluj-Napoca, Cluj-Napoca, Romania. · J Neural Transm Suppl. · Pubmed #12456070 No free full text.

Abstract: BACKGROUND: Cerebrolysin (Cere) is a peptidergic, neurotrophic drug which has been shown to improve cognitive performance and global function of Alzheimer's disease (AD) patients in earlier trials. In this study, we have attempted to replicate this findings with particular emphasis on functional improvement of the patients. PATIENTS AND METHODS: Patients received infusions of 30 ml Cere or placebo five days/week for six consecutive weeks. Patients had to have a diagnosis of AD and a MMSE score of 14-25 inclusive. Effects on cognition, global function, and activities of daily living were evaluated 3, 6, and 18 weeks after the beginning of the infusions. RESULTS: Significant improvement of cognitive function, clinical global impression and activities of daily living were seen after the end of the therapy. The effects were most pronounced in the DAD score, a measure for the capability to perform activities of daily living. Interestingly, and in line with the findings of earlier studies, the treatment effect of Cere was maintained after cessation of treatment up to the week 18 assessment. CONCLUSION: The data confirm the findings of earlier trials and clearly demonstrates that Cere leads to functional improvement of patients with AD. The sustained treatment effect of Cere after withdrawal has been confirmed.

Ruether E, Alvarez XA, Rainer M, Moessler H. · Göttingen University Clinic for Psychiatry, Göttingen, Federal Republic of Germany. · J Neural Transm Suppl. · Pubmed #12456069 No free full text.

Abstract: BACKGROUND: In a recent study, Cerebrolysin (Cere), a compound with neurotrophic activity, has been shown to be effective in the treatment of mild to moderate Alzheimer's disease (AD). A subgroup analysis of this double-blind, placebo-controlled study was performed to assess the effects of Cere in cases with more advanced forms of AD. PATIENTS AND METHODS: Patients received infusions of 30 ml Cere or placebo five days/week for four weeks. This treatment was repeated after a two-months therapy-free interval. Effects on cognition, global function, behavioural symptoms and activities of daily living were evaluated 4, 12, 16, and 28 weeks after the beginning of the infusions. 109 patients with MMSE scores <20 were included in this analysis. RESULTS: The responder rate of the Cere group was 65% on the CGI, compared to 24.5% in the placebo group (p < 0.004). In the ADAS-cog, a score difference of 4.1 points in favour of Cere was observed (p < 0.0001). Notably, improvements were largely maintained in the Cere group up to the week 28 visit. CONCLUSION: The data clearly demonstrate the efficacy of Cere treatment in moderate to severe forms of AD with sustained treatment effects on cognition and global function even after discontinuation of treatment.

Ruether E, Husmann R, Kinzler E, Diabl E, Klingler D, Spatt J, Ritter R, Schmidt R, Taneri Z, Winterer W, Koper D, Kasper S, Rainer M, Moessler H. · Goettingen University Clinic for Psychiatry, Germany. · Int Clin Psychopharmacol. · Pubmed #11552768 No free full text.

Abstract: Cerebrolysin (Cere) is a compound with neurotrophic activity which has been shown to be effective in the treatment of Alzheimer's disease (AD) in earlier trials. The efficacy and safety of repeated treatments with Cere were investigated in this randomized, double-blind, placebo-controlled, parallel-group study. One hundred and forty-nine patients were enrolled (76 Cere; 73 placebo). Patients received i.v. infusions of 30 ml Cere or placebo 5 days per week for 4 weeks. This treatment was repeated after a 2-month therapy-free interval. Effects on cognition and clinical global impressions were evaluated 4, 12, 16, and 28 weeks after the beginning of the infusions using the Clinical Global Impression (CGI) and the Alzheimer's Disease Assessment Scale-cognitive subpart (ADAS-cog). All assessments, including the 28-week follow-up visit were performed under double-blind conditions. At week 16, the responder rate of the Cere group was 63.5% on the CGI, compared to 41.4% in the placebo group (P < 0.004). In the ADAS-cog, an efficacy difference of 3.2 points in favour of Cere was observed (P < 0.0001). Notably, improvements were largely maintained in the Cere group until week 28, 3 months after the end of treatment. Adverse events were recorded in 43% of Cere and 38% of placebo patients. Cere treatment was well tolerated and led to significant improvement in cognition and global clinical impression. A sustained benefit was still evident 3 months after drug withdrawal.

Rainer M, Kraxberger E, Haushofer M, Mucke HA, Jellinger KA. · Memory-Clinic and Psychiatric Department, Donauspital, Sozialmedizinisches Zentrum Ost, Wein, Austria. · J Neural Transm. · Pubmed #11459000 No free full text.

Abstract: Reduced nicotinamide adenine dinucleotide (NADH) is advertised as an over-the-counter product or dietary supplement to treat Alzheimer's disease. We performed a 3-month open-label study with oral 10 mg/day NADH with 25 patients with mild to moderate dementia of the Alzheimer, vascular, and fronto-temporal types in addition to their current cholinomimetic drug medication. In 19 patients who completed the study, we found no evidence for any cognitive effect as defined by established psychometric tests. We conclude that NADH is unlikely to achieve cognitive improvements in an extent reported earlier, and present theoretical arguments against an effectiveness of this compound in dementia disorders.

Grünberger J, Prause W, Frottier P, Stöhr H, Saletu B, Haushofer M, Rainer M. · Abteilung für klinische Psychodiagnostik, Universitätsklinik für Psychiatrie und Psychotherapie, Medizinische Universität Wien. · Neuropsychiatr. · Pubmed #19272292 No free full text.

Abstract: AIM: Pupillometry is a non-invasive measurement technique based on the pupillary response to specific sensoric, mental and emotional variables. After topical application of a cholinergic antagonist (tropicamide) an increased pupillary dilatation response in Alzheimers s disease patients was described ("receptor test"). The aim of the present study was to evaluate the usefulness of the 0.01% tropicamide receptor test in differentiating types of dementia. METHOD: 425 patients (159 men, 266 women, mean age 75 years) of the Memory Clinic of the SMZ Ost Vienna, Austria were included in the study. 195 patients suffered from a dementia in Alzheimer's disease with late onset (ICD-10: F00.1), 42 from dementia in Alzheimer's disease with early onset (F00.0), 71 from vascular dementia (F01), 34 from Lewy-Body dementia (F03) and 83 from mixed dementia (F00.2). All patients were investigated by means of a computer-assisted pupillometer. The pupillary diameter of the left eye was measured 4 times (baseline=0 minutes, after 20, 40 and 60 minutes). 4 minutes after baseline one drop of 0.01% tropicamide solution was installed onto the left eye of the patients. RESULTS: At baseline the pupillary diameter was largest in Lewy-Body dementia, smallest in vascular dementia. Significant differences were observed between vascular dementia and early-onset dementia in Alzheimer's disease as well as between Lewy-Body dementia and all other dementia syndromes (except dementia in Alzheimer's disease with early onset). The 0.01% tropicamide receptor test made it possible to differentiate early-onset dementia in Alzheimer's disease from vascular and mixed dementia. CONCLUSION: Utilizing pupillometry in combination with the 0.01% tropicamide receptor test allows to discriminate between different dementia types of, as demonstrated in our study.

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.

Fischer P, Krampla W, Mostafaie N, Zehetmayer S, Rainer M, Jungwirth S, Huber K, Bauer K, Hruby W, Riederer P, Tragl KH. · Department of Psychiatry and Psychotheraphy, Medical University Vienna, Vienna, Austria. · J Neural Transm Suppl. · Pubmed #17982893 No free full text.

Abstract: The etiology of white matter hyperintensities (WMH) seen on T2-weighted cranial magnetic resonance images is a matter of debate. We investigated deep and periventricular WMH in the brains of a community-based cohort of 532 subjects aged 75-76 years. The objective of this study was to determine whether WMH at age of 75 years were associated rather with vascular factors than with degenerative factors. Arterial hypertension treated with antihypertensive drugs favored WMH, and WMH were found more frequently in subjects with focal vascular lesions. Additionally, we found significant associations between both, deep white matter and periventricular hyperintensities, and focal atrophy of medial temporal lobe structures. The odds ratio for deep WMH in subjects with more severe medial temporal atrophy was 4.4 (95%-CI: 1.9-9.8) that for periventricular hyperintensities was 3.9 (95%-CI: 1.7-8.8). These findings might indicate that not only vascular factors alone but also degenerative factors favor the occurrence of WMH after the age of 75 years.

Rainer M, Krüger-Rainer C. · Psychiatrische Abteilung und Memory Clinic, Donauspital im SMZ-Ost der Stadt Wien, Langobardenstrasse 122, 1220 Wien, Osterreich. · Wien Med Wochenschr. · Pubmed #14733062 No free full text.

Abstract: Despite the fact that 9% of the elderly would need psychotherapeutic treatment, only 1% of the applications for such treatment were initiated by the elderly. Older people often lack the ability to verbalize their emotional problems, which is an obvious prerogative for expressing the wish for psychotherapy. However elderly people tend to indulge in childhood memories, and therefore would be excellent candidates for psychoanalytic-orientated treatment. Because objective time is not a factor in subconscious life, older people can suffer from unsolved intrapsychic-, intra- and intergenerational conflicts and trauma reactivations. Without considering these psychological conflicts, the most important fields for psychotherapeutic intervention in the elderly are depression, mild cognitive impairment, incipient demential syndromes, and the impairment of psychosocial competence resulting from these conditions; caregiver-related therapy also plays an important role. For those between 65 and 75 years of age, the indications for psychotherapy are similar to those of younger adults: first of all depression, anxiety-syndromes, insomnia and suicidal attempts. For those over 75 years old, isolation, polymorbidity, preservation of autonomy and self-determination, and the fear of loosing autonomy and becoming care-dependent are the most important indications for psychotherapy. A feature common to all psychotherapeutic schools is that they try to overcome disturbances, to reduce emotional pain, to preserve, establish and improve psychosocial competency and the activities of daily living. Psychotherapy in a narrow sense is indicated when the psychic structure, the mental flexibility and the motivational state are quite good and if differentiated verbal interactions are possible. In a broader sense, psychotherapy stands for actional and training aspects, and integral environmental and socio-therapeutic treatment so that autonomy and quality of life can be properly improved. This definition of psychotherapy makes it obvious that demented and care-dependent patients are potential candidates for psychotherapy.

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%.

Rainer M, Jungwirth S, Krüger-Rainer C, Croy A, Gatterer G, Haushofer M. · Sozialmedizinisches Zentrum Ost, Memory Clinic und Psychiatrische Abteilung, Wien, Austria. · Psychiatr Prax. · Pubmed #11961715 No free full text.

Abstract: OBJECTIVES: The enclosed paper tries to encompass the relatives of patients of three different geriatric groups diagnosed. It tries to establish the difference in care and which special factor influences each group concerning the burden of care. PATIENTS: Comparison of three groups: 1. Alzheimer-dementia, 2. vascular-dementia, 3. nondemented patients. RESULTS: It was found that it is mostly partners and children who are the carers in all three groups diagnosed. The social behaviour of the Alzheimer patient is the most stressful part of caring. The relatives of patients with vascular dementia are most stressed by disturbing behaviour and memory impairment and the relatives of the non dementia group by impaired mood and inadequate behaviour. CONCLUSIONS: The burden of care is the hardest for the relatives of the Alzheimer patients. For all three groups diagnosed the non cognitive symptoms are the main factor of the carers burden.

Rainer M, Krüger-Rainer C, Croy A. · Memory-Clinic und psychiatrischen Abteilung des Donauspitals im SMZ-Ost der Stadt Wien. · Wien Med Wochenschr. · Pubmed #11925770 No free full text.

Abstract: Beside the loss of the memory capacity, non-cognitive disturbances occur up to 70%-90% in patients suffering from Alzheimer's disease due to pathological changes in the brain. Delusion, hallucination and changes of the circadian rhythm can appear in addition to the five kinds of disorder--agitation, aggressive behaviour, screaming, depression and constant hyperkinesia. The consequences of these changes in perception and behaviour constitute severe problems for the patient as well as for the main caregiver. The burden of caring often exceeds their energy and resources. Not only do many of those caregivers suffer themselves from exhaustion but also from feelings of guilt and depression. The therapeutic concept includes the involvement of the relatives through information, support, counselling and guidance as much as the investigation of the causes and interrelation of the problematic behaviour in each individual case and further involves the carer in creating a concept to deal in an optimal way with the patient.

Rainer M, Mucke HA, Krüger-Rainer C, Kraxberger E, Haushofer M, Jellinger KA. · Memory-Clinic and Department of Psychiatry, Donauspital, Sozialmedizinisches Zentrum Ost, Vienna, Austria. · J Neural Transm. · Pubmed #11768631 No free full text.

Abstract: In a cross-sectional study of outpatients diagnosed with dementia of the Alzheimer type who had been treated with a broad variety of drugs supposed to improve cognition or to delay cognitive decline, we have investigated the effects of abruptly discontinuing therapy on cognition. Termination of therapy with any cholinesterase inhibitor was associated with a cognitive decline during the following 6-7 weeks which was significantly more pronounced than that experienced by patients who had received nootropic drugs or calcium channel blockers (3.41 vs. 1.17 points on the ADAS-Cog scale; -1.14 vs. -0.06 points on the MMSE scale). This effect was not modified by gender, apolipoprotein E genotype, or the extent of ventricular enlargement on CT scans. Its magnitude was comparable to the cognitive response observed in published clinical trials when cholinesterase therapy commenced, and also with the data obtained during a 6-week placebo washout phase.

Grünberger J, Linzmayer L, Walter H, Rainer M, Masching A, Pezawas L, Saletu-Zyhlarz G, Stöhr H, Grünberger M. · Department of Psychiatry, University of Vienna, Vienna, Austria. · Neuropsychobiology. · Pubmed #10420100 No free full text.

Abstract: Memory loss and severe cognitive deficits in Alzheimer patients are supposed to be related to a reduction of acetylcholine as well as to central nervous deactivation. For the investigation of cholinergic deficits and deactivation, we used computer-assisted pupillometry. Cholinergic deficits caused by a particularly severe loss of cholinergic neurons may be responsible for cognitive and mnemonic performance deficits. The control of the pupillary diameter represents a balance between cholinergic and adrenergic innervation and is influenced directly or indirectly by central and autonomic nervous system inputs. Either of these systems could be affected in Alzheimer patients. A reduced innervation of the target muscle through neuronal cell death, axon retraction, reduced release, increased reuptake of altered amounts or function of neurotransmitter receptors seems to affect the pupillary response to cholinergic antagonists in Alzheimer patients. There is, however, no relationship between pupillary diameter and central deactivation, but between central nervous activation and pupillary oscillations which reflect the physiological corticodiencephalic activity, a relationship has to be assumed. Frequencies and amplitudes of pupillary oscillations measured by means of Fourier analysis are modulated corticodiencephalically. Therefore, Alzheimer patients were compared to healthy controls with respect to their pupillary diameters and responses to an acetylcholine antagonist. Twenty-nine patients, aged between 55 and 85 years, suffering from mild to moderate Alzheimer's disease (AD) and 29 normal controls of similar age (56-85 years) participated in the study. The cholinergic receptors of the pupil were blocked by the acetylcholine antagonist tropicamide. It could be assumed that the larger the pupillary dilatation, the larger the extent of cognitive deficits. Alzheimer patients show abnormal acetylcholine neurotransmission. Changes of pupillary diameter after instillation of 1 drop of 0.01% tropicamide solution were measured and Fourier analysis of pupillary oscillations was performed. Times of measurement were: 0 (baseline), 20, 40, 60, 80, and 100 min. After 4 min tropicamide was instilled. Forty min after the instillation of tropicamide into the left eye, the Alzheimer patients showed a pronounced dilatation of 41.57%. The dilatation in normal controls was 28.5%. Fourier analysis of pupillary oscillations (sum of frequency bands = power) demonstrated a marked deactivation (low amplitudes in low-frequency bands, but in contrast to our expectations no higher amplitudes in the higher frequency bands) in patients with AD which remained constant at all times of measurement. By means of discriminant analysis of pupillary diameter and pupillary oscillations (frequency band 0.00-1 Hz), 89. 7% were correctly predicted to be Alzheimer patients, 89% to be normal controls.

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.