Marcel Bahro

Longitudinal stability of CSF tau levels in Alzheimer patients

BACKGROUND Antemortem levels of tau in the cerebrospinal fluid (CSF) of Alzheimers disease (AD) patients have repeatedly been demonstrated to be elevated when compared to controls. Although CSF tau has been reported to be elevated even in very mild AD, it is unknown how tau levels change during the course of the disease. METHODS We have followed 29 mild-to-moderately affected AD subjects over 2 years with repeated CSF taps. Clinical measures of dementia severity (Clinical Dementia Rating Scale, Global Deterioration Scale and Mini-Mental Status Examination) were obtained at the start and conclusion of the observation period, and CSF tau was measured with a standard enzyme-linked immunoabsorbent assay (ELISA) using two monoclonal antibodies. RESULTS Despite significant changes in the clinical measures consistent with progression of the disease, no significant overall change in CSF tau levels (548 +/- 355 vs. 557 +/- 275 pg/mL, NS) was observed. None of the clinical variables was significantly correlated with either baseline measures of CSF tau or delta CSF tau (last-first). Similarly, CSF tau at baseline and changes over time were not significantly related to Apolipoprotein E (APO E) phenotype. CONCLUSIONS These data suggest that CSF tau levels are stable over extended periods of time in a group of mild-to-moderately demented AD subjects and that CSF tau levels do not predict the severity or rate of progression of AD, at least not during the middle stages of the illness.

How Do Patients with Alzheimer's Disease Cope with Their Illness? - A Clinical Experience Report

ost current research on dementia focuses primarily on M biological issues linked to etiology and pathogenesis. In addition, there has been research focusing on other, related aspects of dementia, including behavior and therapeutic treatment approaches, care settings for demented patients, and the needs and problems that confront the caregivers of affected subjects.’ Little, however, has been published about the psychodynamic effects on the patients themselves of this devastating range of illnesses.2” Alzheimer’s disease (AD) is a particularly malignant form of dementia in that it attacks personality and character, and, therefore, tremendously erodes any remaining coping strategies. A review of the literature confirms that the psychodynamics of AD have been largely overlooked by a research community that is, perhaps, more familiar with mechanisms for observing objective, measurable ratings of behavioral or biological criteria. There are fewer studies on the phenomenology of AD patients’ subjective experiences, their individual beliefs or self-perceptions.lV6 Hence, the purpose of this article is to describe what we have learned from our patients about their psychological response to the continuous deterioration imposed by their illness. We report on seven patients with mild to moderate states of probable AD, in order to describe their various adjustment strategies, as well as their changing internal sense of reality. What is their perception of the disease? In what ways are they at all aware of it? What explanations do patients offer for their diminished abilities? What is their outlook for the future? In answer to these questions, the case reports demonstrate that a range of defense mechanisms is utilized by each of the subjects regarding the cause, symptoms, and prognosis of AD. This is not intended as an experimental study. Rather, it is a descriptive account of the authors’ experience at a large institution for the treatment of mentally ill geriatric patients where we were able to observe our patients’ coping strategies and to record their description of their own ‘inner world.’ We believe it is both important and timely to share such case material with colleagues in the field. Such observations can result in improving the care of patients with AD by providing an understanding of, as well as a tolerance for, the adaptive function of behaviors that, otherwise, might be perceived only as troublesome manifestations of the illness.

REM Sleep Parameters in the Discrimination of Probable Alzheimer's Disease from Old-Age Depression

Thirteen dementia of the Alzheimer type (DAT) patients and fifteen old-age major depressive disorder (OAD) patients were investigated by polysomnography. The sleep was recorded during two nights after a 1 week wash-out period of psychotropic drugs. No statistically significant differences between the two groups were found concerning sleep continuity or architecture. The amount of REM sleep was significantly lower in DAT in comparison with OAD patients (11.7% verses 18.5%). Also, total REM density as well as the density of the first REM period were significantly lower in the DAT compared with the OAD patient group (15.8% verses 32.5%, 14.9% verses 38.1%, respectively). REM latency did not differ between both groups. Because REM latency is known from other studies to be shortened in depressed patients due to a cholinergic hyperactivity, the opposite finding, i.e., prolongation of REM latency, was expected for DAT patients. This assumption, however, could not be confirmed in the present study. It is concluded that REM density may better differentiate between DAT and OAD.

The Effect of Carbamazepine on Endocrine and Sleep EEG Variables in a Patient with 48-Hour Rapid Cycling, and Healthy Controls

Carbamazepine treatment of a patient with 48-hour rapid cycling led to a dampening of mood cycling, and prolonged rapid eye movement (REM) sleep latency. No effect on central alpha-receptors as measured by growth hormone (GH) secretion after clonidine stimulation or on spontaneous 48-hour GH secretion was observed. In 12 healthy subjects given 400 mg carbamazepine daily for a period of 5 days, improved sleep continuity and increased slow-wave sleep occurred with treatment. REM sleep percentage and REM latency remained uninfluenced, whereas REM density decreased. GH secretion after clonidine stimulation was not altered. Data from the single-case longitudinal study emphasize that carbamazepine is effective in treating rapid-cycling affective psychosis. Furthermore, neuroendocrine and sleep EEG data from the study in healthy subjects indicate a different profile of action for carbamazepine compared to most other antidepressants or antimanic drugs.

Interactions of prefrontal cortex during eyeblink conditioning as a function of age

Changes in regional cerebral blood flow (rCBF) in eleven elderly subjects during pairings of tone and air puff were compared to rCBF changes during pairings in young subjects. Although all subjects reported being aware of the relationship between tone and air puff, elderly subjects did not condition as well as young subjects and their rCBF measures were attenuated. Covarying the performance differences between young and old subjects did not change this conclusion suggesting that differences in neural activation during learning are related to binding of CS-US information prior to the impact of the association on performance. Both groups showed learning-specific rCBF changes in cerebellum, inferior right prefrontal cortex and posterior cingulate. However, only in young subjects were there learning-specific changes in rCBF in left temporal cortex, midbrain, caudate, and inferior left prefrontal cortex. Analysis of learning-dependent patterns of functional connectivity of inferior left prefrontal cortex showed only young subjects had a strong left prefrontal functional connectivity with cerebellum, hippocampus, thalamus and temporal cortex. Thus, beyond changes in regional activity, these data also suggest that age may alter the operations of functional networks underlying learning and memory.

Dreams and dreaming among the elderly: An overview

This paper reviews past and current research into the dreams and dreaming of people over 65 years of age. Recent studies have shown, for example, that frequency of dream recall declines with age in both men and women, but that the main decrease occurs in early middle age and is thus unlikely to be connected with aging effects.The results of studies having to do with dream tone, active/passive stance and typical dream themes are less conclusive.This paper also surveys the attitudes toward dreams one encounters among the elderly, the temporal references in their dreams and the use of dreams in the psychotherapy of aged and aging persons and concludes by considering the dreams of those at the end of their life.

Oestrogens and Alzheimer's disease

In the last decade, several reports suggest that oestrogen replacement therapy (ORT=ERT=estrogen replacement therapy) might prevent or delay Alzheimers disease. Oestrogens influence and modulate brain structure and brain function. There are substantial arguments that the postmenopausal oestrogen loss might, together with other factors, accelerate the appearance of Alzheimers disease. The evidence is suggestive, but not compelling, that ORT can reduce the relative risk to suffer from Alzheimers disease. Furthermore, recent findings are consistent with the hypothesis that oestrogens might ameliorate the symptomatology in early stages of Alzheimers disease. However, it has to be remembered that in most clinical trials the number of oestrogen users was quite small, and, usually, oestrogen use was not randomised. The aim of the present review is to discuss the data available today in view of their clinical relevance. Copyright

The Effects of Scopolamine on Changes in Regional Cerebral Blood Flow during Classical Conditioning of the Human Eyeblink Response

We examined the effects of scopolamine on the functional anatomy of classical conditioning of the human eyeblink response. Ten healthy young normal female volunteers (mean age ± SEM: 26.7 ± 0.9 years) were administered 0.4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H215O. Scans occurred during three sequential phases: (1) explicitly unpaired presentations of the unconditioned stimulus (airpuff to the right eye) and conditioned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stimuli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 ± 4.9%) relative to 18 untreated subjects from two previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, the right inferior occipital cortex, the right lateral temporo-occipital cortex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant relative decreases in rCBF were measured in the thalamus, the left putamen/insula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebellar cortex, the insula and the lateral temporo-occipital cortex. Our finding of decreased rCBF in the thalamus and increased rCBF in the occipital cortex may be attributable to effects of scopolamine per se rather than conditioning. Our data lend further support to the notion that classical conditioning involves distributed changes in multiple systems within the central nervous system.

Reliability in dream research: a methodological note.

The coefficients of internal consistency and retest reliability had been rarely investigated within the methodology of dream content analysis. Analyzing a dream series of elderly, healthy persons obtained from weekly telephone interviews, the internal consistency of a series of 20 dreams and retests after 4 or 22 weeks, respectively, had been computed. The findings indicate that dream recall and dream length are quite stable, but dream characteristics such as bizarreness and emotional tone underlie large intraindividual fluctuations. In order to obtain reliable measures for these variables which will be important for correlational studies, including waking-life trait measures, one has to obtain as many dreams as possible (about 20) in a very short time period. Further research is needed to extend the present findings to diary dreams and laboratory dreams.

Boundary Questionnaire Results in the Mentally Healthy Elderly

The Hartmann Boundary Questionnaire was administered twice, with six months in between, to 61 Swiss subjects over 60 years of age taking part in an investigation into the effects of dream-telling on five variables: well-being, sleep quality, sleep duration, dream recall and dream tone. In addition, dream epoch, i.e., the age of life of the dreamer as perceived in the dream, was recorded for those who told dreams. In addition to this study group in which the members told dreams there were two control groups. Those in the first control group were asked about well-being and sleep quality but not about dreams or dreaming, while those in the second control group were additionally asked how many dreams they had retained, how frequently they had occurred and about the dream tone (pleasant/unpleasant). All study participants were given the Hartmann Boundary Questionnaire at the beginning (pre-test) and again at the end of the six month study period (post-test). The retest reliability was high (r = 0.872 for the whole sample). We report here the relationships obtained between the questionnaire scores and age, group membership, gender and the number of dreams that were retained over a 26 week testing period. No significant correlations were found for age, group membership or dream recall. There was, however, a small, significant boundary score difference between women and men for the pre-test, indicating thinner boundaries for women, but this difference was no longer significant in the post-test.