[Prevention of dementia (including Alzheimer's disease)]. / Prävention von Demenz (einschliesslich Alzheimer-Krankheit).

Prevention of dementia: Life expectancy still increases linearly, and the elderly part of the European population grows rapidly in relation to the young. Dementia, however, grows even more rapidly, because it increases exponentially after age 65; it will become a great burden if nothing is done. The discussion so far is concentrated on treatment, whereas prevention is neglected. The therapy of dementia, however, has limited effect. Contrary to a widespread opinion prevention is possible. Genetic factors alone dominate the fate of cognition only in about 3 % of the cases. Besides age, lifestyle and the vascular risk factors exercise a great influence. High blood pressure carries a fourfold risk, diabetes more than doubles the risk both of the vascular and of the Alzheimer type; combined even more. Especially cerebral microangiopathy is strongly associated with Alzheimer's dementia, it triggers the vicious circle which leads to amyloid deposition. The importance of the circulation is underestimated, because most of the microvascular cerebral lesions are not perceived by the patient. All the risk factors for Alzheimer's disease after age 65 are also vascular risk factors especially for microangiopathy: Apo-E4, oestrogen deficiency, insulin resistance, diabetes, arterial hypertension, high cholesterol, old age and increased plasma homocystin which is often caused by alcohol consumption even in moderate doses. A healthy life style with daily outdoor activity and a Mediterranean diet not only reduces the risk of dementia, but also of coronary death and cancer. Cognitively stimulating activity protects even more than physical activity against dementia; the basis for this is acquired in youth by education. Therapy with statins is advisable if atherosclerosis cannot be reasonably counteracted by physical activity and diet.

Bereitschaftspotential in amyotrophic lateral sclerosis (ALS): lower amplitudes in patients with hyperreflexia (spasticity).

In a pilot study the Bereitschaftspotential (BP) was investigated in 16 patients suffering from amyotrophic lateral sclerosis (mean age 58.6, mean severity of the illness according to Norris ALS score 76.4 points). Comparing the total ALS group (n=16) with matched controls no significant differences in the BP amplitude parameters were found. However, a subgroup of 7 ALS patients with signs of pronounced spasticity (hyperreflexia) differed significantly at the central midline from matched controls and significantly in addition from patients with a lower degree of spasticity. Controls as well as patients with a lower degree of spasticity had significantly higher BP amplitudes at the midline (electrode positions Cz and Pz, P<0.05, H-test). The correlation coefficient between the hyperreflexia Norris score and the various BP parameters for the total ALS sample (n=16) revealed a significant correlation especially over the midline. Stronger signs of spasticity (hyperreflexia) are associated with lower amplitudes of the BP.

Electrophysiological analysis of expectancy: P3 in informed guessing.

18 healthy subjects had to guess, which of two nonequiprobable events would occur next. Each trial was preceded by a cue which increased the probability of the corresponding event as compared to its global probability. Event-related potentials (ERPs) were recorded and then classified according to global probability of events, their relation to the preceeding cue (valid versus invalid cues) and to subject's prediction (predicted versus nonpredicted). Two late positive waves (P350 and P550) with parietal maxima were distinguished. Both waves had larger amplitudes in response to improbable events than to highly-probably events. Similarly, both had larger amplitudes following invalid cues than following valid cues, and this difference was larger in those subjects who tended to follow the cue than in those who tended to reject it. No difference in terms of ERP component amplitudes was found between predicted and unpredicted events; however, the latency of the P350 peak was longer following unpredicted events. Taken together with data of the literature, the present results indicate that ERP allow us to distinguish between two meanings of the word "expectancy": (1) the rule-related expectancy as cognitive estimation of the likelihood or "representativeness" of an event (based on grasping event contingencies), and (2) the goal-related expectancy manifested in the subject's overt behavior. Only the former "expectancy" affects the amplitude of the late positive wave ("P3"), while the latter does not.

Visually-guided saccadic eye movements in adolescents at genetic risk for schizophrenia.

Visually-guided saccades of 21 offspring of schizophrenic parents and 21 individually matched controls were compared with regard to the frequency of occurrence of saccadic hypometria and hypermetria, non-fixations, and omissions of target jumps. Target steps ranged from 10 to 60 degrees, and interstimulus intervals averaged 2.5 s; subjects were promised financial reward depending on performance. Recordings were carried out at the subjects' homes. To screen for cognitive abilities and psychopathological behavior, subjects were tested by means of an intelligence scale and a behavioral checklist. With large target steps (40-60 degrees), the high-risk group made significantly more grossly hypometric saccades (gain < or = 0.8) than the control group; responses to small target steps (10-30 degrees) exhibited a similar, albeit statistically not significant, trend. There were no significant differences with regard to the occurrence of hypermetria. Non-fixations scored marginally higher in the high-risks as compared to controls, but this was again not a significant difference. The incidence of omissions of saccades was very low in both groups. The results of the study suggest that subjects at genetic risk for schizophrenia may differ from controls by an increased incidence of conspicuously hypometric saccades. Clearly, this difference is not caused by a deficit of the saccadic motor circuitry proper; comparison to control data obtained with a similar experimental protocol suggests that it probably reflects an impaired internal control of saccades in the presence of distraction and stress. The relevance of saccades as indicators of a possible schizophrenic vulnerability is discussed.

The effects of therapy on spasticity utilizing a motorized exercise-cycle.

UNLABELLED: F-wave amplitudes have been used to demonstrate changes of motor neuron excitability in patients receiving pharmacological antispastic therapy as well as in those having physiotherapy. In this study it is shown that F-wave amplitudes can also be used to document changes of motor neuron excitability as an effect of the therapy with a motorized exercise-cycle, which moves the legs of paraplegic patients in a way similar to cycling. Ten F-waves were recorded immediately before and after the therapy with a motorized exercise-cycle in 70 legs of 35 patients with spastic paraparesis. Mean F-wave amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were significantly lower after therapy than before. CONCLUSION: The antispastic effect of the therapy with a motorized exercise-cycle may be documented by a decrease of F-wave-amplitude parameters.

Selection of electrophysiological techniques to investigate axonal damage of peripheral motor nerve fibres.

After an acute peripheral nerve injury fibrillations and positive sharp waves can be registered in the denervated muscle. The time delay between injury and the manifestation of detectable electrophysiological alterations using conventional electromyography (EMG) lessens the diagnostic value for early treatment. We demonstrate that in radicular lesions the electromyographic examination of the paravertebral musculus multifidus allows diagnosis earlier by about a week compared to examination of limb muscles. Using the amplitude reduction of the compound muscle action potential (CMAP) after stimulation of the nerve distal to its lesion a further reduction of the delay for electrophysiologic proof in peripheral as well as in radicular lesions is possible. Based on these findings we propose a selective strategy using the decline of the CMAP starting with the third day after a peripheral nerve lesion, the electromyography of the deep paravertebral muscles in radicular lesions beginning at the end of the first week, and the conventional EMG investigation of limb muscles after two weeks following the injury.

[Electrophysiologic correlates of selective attention in children and adolescents at increased risk of schizophrenia]. / Elektrophysiologische Korrelate selektiver Aufmerksamkeit bei Kindern und Jugendlichen mit erhöhtem Schizophrenie-Risiko.

Electrophysiological correlates of selective attention in children and adolescents at high risk for schizophrenia. As part of a research project on electrophysiological correlates of attention in young subjects at high genetic risk for schizophrenia, auditory event-related potentials (ERPs) associated with selective attention and automatic information processing were recorded in 21 adolescent (offspring of at least one parent with schizophrenia) and 21 control subjects matched for age, sex and socioeconomic status. The experimental task was a dichotic listening task, and accuracy of counting target pips served as a psychometric control variable. The results showed group-related differences in the ERPs, with a significant reduction being present in the high-risk group concerning the amplitude of the fronto-precentrally located negative difference (Nd) wave and the F3 component elicited by selectively attended stimuli. Comparison of individual matched pairs showed that reduced Nds, characterized 14/21 high-risk individuals and reduced P3s 16/21. Moreover, there were significant correlations between ERP reductions and psychometric deficit (counting accuracy). Finally, 13 latencies tended to be prolonged in the high-risk group. Mismatch negativity (MMN), an ERP correlate of automatic information processing, did not differ significantly in the two groups, although there was a marked reduction in amplitude in the high-risk group. The ERP alterations point to impaired selective attention in a considerable proportion of subjects at high genetic risk for schizophrenia.

Effects of physiotherapy on F-wave-amplitudes in spasticity.

F-wave amplitudes have been used to demonstrate changes of motor neuron excitability in spasticity and pharmacological antispastic therapy. In this study it is shown that F-wave amplitudes can also be used to document changes of motor neuron excitability as an effect of physiotherapy. Ten F-waves were recorded immediately before and after physiotherapy in 42 legs of 21 patients with spastic paraparesis due to multiple sclerosis. Mean F-wave amplitude, maximum F-wave amplitude, mean F-wave/M-response ratio and maximum F-wave/M-response ratio were significantly lower after physiotherapy than before. Therefore the antispastic effect of physiotherapy is documented by a decrease of F-wave-amplitude parameters.

Event-related brain potentials in a varied-set memory search task: a reconsideration.

Event-related potentials (ERPs) were recorded in 19 healthy subjects as they completed two Sternberg (1969, American Scientist, 57, 421-457) memory tests. In separate sessions, either single digits (i.e., 0-9) or 10 abstract figures were used as stimuli. In both sessions, memory set sizes were 1 (M1), 2 (M2), or 4 (M4). The amplitude and latency of the parietal P400 and the frontocentral negativity preceding P400 varied significantly with set size, but only between M1 and M2, whereas reaction time increased dramatically from M1 to M2 and from M2 to M4. These findings challenge previous assertions that the ERPs reflect aspects of the exhaustive serial search proposed by Sternberg. A late parietal positivity (P620), which failed to vary with set size, was larger in response to figures than to digits and may represent the search for, or utilization of, semantic traces of the stimuli.

Preattentive information processing as measured by backward masking and texton detection tasks in adolescents at high genetic risk for schizophrenia.

Schizophrenic patients have consistently been reported to show deficits in preattentive information processing as demonstrated by impairments in visual backward masking and texton detection tasks. Texton detection refers to Julesz's texton theory, which defines a certain limited number of texton elements (e.g., one 'L' among many '+') that can be detected readily and simultaneously without attentional effort irrespective of the size of the rest of the visual field. The present study investigated whether deficits of preattentive information processing are more prevalent in a group of adolescents of high genetic risk for schizophrenia compared to matched control subjects. Although differences in the performance in visual backward masking tasks could not be detected with our experimental approach, preattentive texton detection was to a certain extent disturbed in subjects at risk. Moreover, subjects at risk did not show the advantage of the right hemisphere in processing texton elements which was found in the control group. This may point to a subtle dysfunction of the right hemisphere in the risk group. It is concluded from the present study that deficits in preattentive texton detection may represent an indicator for a schizophrenic disposition. However, further studies including other high risk groups, schizophrenics in remission and individuals with a schizotypal personality disorder are needed to confirm this hypothesis.

Propionibacterium acnes in the cortex of patients with Alzheimer's disease.

Propionibacterium acnes was found in the cortex of three patients with Alzheimer's disease and in one frontal cortex of an elderly patient with cardiovascular risk factors and hypoxia due to a large glioblastoma of the right frontal lobe with severely increased intracranial pressure. Propionibacterium acnes is an atypical anaerobic bacterium which is sensitive to cephalosporins, but insensitive to metronidazole. It is concluded that a capillary microangiopathy (in consequence of old age and cardiovascular risk factors such as high blood pressure) leads to cortical hypoxia and reduced resistance of the cortical immune system. Prevention by dietary regimes counteracting microangiopathy and treatment with cephalosporins are recommended.

Changes in EEG order in neuroleptically treated normal volunteers during a voluntary movement task.

15 normal volunteers were treated over three weeks with haloperidol (HAL) and in the third week additionally with biperidene (BIP). The order of the EEG spectra at different topographical locations and in different frequency bands during a movement task was analyzed using uncertainty analysis (UA), a multivariate analysis technique based on information-theoretical methods. Different patterns of drug-induced changes were found. HAL decreases the theta and alpha band order at the fronto-central lateral areas but increases it at the fronto-central midline in the theta band and at the parietal areas in the alpha band. With the exception of the fronto-central midline locations, BIP more or less counterbalances the effect of HAL. Volunteers felt unwell and had motor disturbances during HAL and felt well again during HAL + BIP. Reaction time values were increased during HAL and normalized during HAL + BIP.

Cerebral magnetic resonance imaging pathology and cerebro-spinal fluid protein in sporadic amyotrophic lateral sclerosis (sALS).

In 3 out of 20 patients with sporadic amyotrophic lateral sclerosis (sALS), cranial magnetic resonance imaging detected multiple demyelinating lesions. All 3 patients died from definite upper and lower motor neuron degeneration. In all 3 cases total cerebro-spinal fluid (CSF) protein remained within normal ranges, and a blood-CSF barrier dysfunction was not detectable. In one of the patients multifocal CNS demyelination coincided with an intrathecal synthesis of immunoglobulin-G and autochthonous CSF oligoclonal IgG banding (OCB) early in disease. Neither absolute or age-corrected survival nor disease progression differed for patients with and without cerebral MR lesions, or normal vs. elevated CSF total protein. Evaluating the CSF in an extended patient sample (n = 29), we found the total CSF protein elevated in 5 of 16 men and none of 13 women (p < 0.05). The mean age-corrected CSF protein content [practical reference limit = (age x 3.3) + 300 mg/l] was higher in male (465 mg/l +/- 32 SE) than in female (350 mg/l +/- 26 SE) sALS patients (p < 0.01). This coincides with a male preponderance in sALS.

Cerebrospinal fluid and serum from patients with inflammatory polyradiculoneuropathy have opposite effects on sodium channels.

The effects of cerebrospinal fluid (CSF) and serum from patients having Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) on voltage-dependent Na+ channels were compared. Bathing human myoballs in CSF substantially reduced their Na+ currents (by > 40% with 8 of 10 patients) elicited at 1 Hz under whole-cell recording conditions. This was because, at the resting potential, more Na+ channels were inactivated (left-shift of the h infinity curve). CSF from patients with other neurological diseases (OND) produces a similar, but smaller, effect. In contrast, serum samples from the same GBS and OND patients caused an increase of the Na+ currents by reducing the number of Na+ channels inactivated at the resting potential. This right-shift of the h infinity curve is in part explained by the effect of serum albumin. We confirm that the CSF of most GBS and CIDP patients contains factors inhibiting voltage-dependent Na+ currents. There is no indication that such factors are effective in the serum of these patients.

Sporadic ALS/MND: a global neurodegeneration with retroviral involvement?

Sporadic amyotrophic lateral sclerosis may be an aetiologically heterogenous disease. We confirmed elevated circulating IgG immune complexes, and altered IgG seroreactivities against human retroviral antigens (HIV-2 and HTLV immunoblots) in overlapping subgroups of patients. Together with preliminary findings of a positive polymerase chain reactivity for human T-lymphotropic virus (HTLV.tax/rex) in blood leukocytes of 5 out of 14 sALS patients, we interpret this as evidence for a retroviral involvement in this relentlessly progressive, often asymmetrically spreading neurodegeneration. The possibility of a secondary phenomenon seems unlikely, yet cannot be completely ruled out.

Improved event-related potential signs of selective attention after the administration of the cholecystokinin analog ceruletide in healthy persons.

Cholecystokinin (CCK) is co-localized with dopamine (DA) in neurons of the mesolimbic-frontocortical dopamine (DA) system, considered essential for the pathology of psychotic behavior and associated attention deficits. The present experiments in 13 healthy men aimed at examining the effects of the CCK analog ceruletide on attention as reflected by event-related brain potentials (ERPs). Subjects were tested according to a double-blind cross-over design on three occasions, following intravenous infusion of placebo, 0.5 microgram ceruletide, and 2.5 micrograms ceruletide. ERPs were recorded during the subject's performance on an auditory selective attention task including the concurrent presentation of frequent standard tones and infrequent deviant tones which the subject had to listen to, or to ignore. The processing negativity (PN) over frontocentral cortical areas, reflecting selective attention, was higher after ceruletide than placebo, this increase being most pronounced after the 2.5 micrograms dose (placebo -1.29 +/- 0.38 microV versus ceruletide -3.02 +/- 0.65 microV, p < .05). ERP signs of a general increase in cortical arousal after ceruletide did not reach significance. Likewise, mismatch negativity, an indicator of preattentive processing of stimulus deviance, was not significantly affected by the peptide. The results indicate that ceruletide affects human brain function primarily by improving selective attention.

Comparative assessment of saccadic eye movements, psychomotor and cognitive performance in schizophrenics, their first-degree relatives and control subjects.

This study is aimed at detecting biological markers for schizophrenia. For this purpose, a total of 70 subjects (21 schizophrenic patients, 27 first-degree relatives and 22 controls) performed a series of tests assessing various attentional, psychomotor and cognitive functions and saccadic eye movements. The schizophrenics performed significantly poorer than both high-risk and control subjects in most of the tests demanding attention, concentration and psychomotor speed (d2 concentration test, reaction times and Stroop test of perceptual interference) as well as cognition (Wechsler intelligence scales). On the other hand, these tests did not differentiate between the high-risk and control subjects. This distinction, however, could be made by two other parameters: hypometria score of saccadic eye movements and ratio of verbal to performance intelligence scores. Both parameters were significantly increased in both the schizophrenic and the high-risk group, distinguishing both from the control group. The relevance of these findings in indicating a schizophrenic disposition is discussed.