CSF beta-endorphin-like immunoreactivity in delirium.

Cerebrospinal fluid beta-endorphin-like immunoreactivity (CSF BLI) was determined for 69 patients who met DSM-III criteria for delirium and for 8 controls. The CSF BLI was significantly lower in the delirious patient group than in the controls (12.5 +/- 3.0 pg/ml versus 15.0 +/- 3.4 pg/ml, p less than 0.05). CSF BLI had no correlation with age or neuroleptic drug dosage, but did have a significant positive correlation with cognitive functioning as evaluated by the Mini-Mental State. Our findings suggest a role for beta-endorphinergic dysfunction in the development of delirium.

Dopaminergic system and monoamine oxidase-B activity in Alzheimer's disease.

The possible involvement of dopaminergic neurons in dementia of Alzheimer type (AD/SDAT) was studied in autopsied brains from 20 patients with AD/SDAT. Dopamine (DA) concentrations were decreased significantly in the temporal cortex, hippocampal cortex and hippocampus in AD/SDAT patients. Levels of homovanillic acid (HVA) were not altered compared to controls. The HVA/DA ratio was significantly higher in the hippocampus of AD/SDAT patients, suggesting overactivity of the remaining DA neurons. Histological findings of substantia nigra suggesting coexistent pathology of Parkinson's disease (PD) found in 25% of cases were associated with lowered levels of DA in striatum and with reduced HVA in CSF. The activity of monoamine oxidase-B was significantly increased in the cortical areas and in the hippocampus, obviously reflecting the underlying cell loss and substantial gliosis in these areas of the brain. In general, DA neurons seemed to be only mildly involved in AD/SDAT. Coexistent PD pathology can explain the loss of DA in the striatum and the presence of clinical PD symptoms in some patients with AD/SDAT. Otherwise the clinical relevance of these dopaminergic alterations is unclear.

Ubiquinone and nicotinamide treatment of patients with the 3243A-->G mtDNA mutation.

The efficacy and safety of ubiquinone (Q10) and nicotinamide were evaluated in a 6-month open-label trial in patients with the 3243A-->G mitochondrial DNA mutation. Blood lactate and pyruvate concentrations decreased, but there was little clinical improvement. Q10 and nicotinamide were well tolerated, but two patients died suddenly and unexpectedly during the trial. These deaths may have been unrelated to treatment. The unpredictable course of the disease makes evaluation of the clinical response difficult.

Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland.

Aging has multiple effects on memory in normal subjects. However, information on the prevalence of age-associated memory impairment (AAMI) is scanty. We studied the prevalence of AAMI in a randomly selected population of 1,049 subjects aged 60 to 78 years from eastern Finland. Research criteria proposed by the National Institute of Mental Health (NIMH) Work Group were applied. We calculated prevalence rates for AAMI by the inclusion criteria alone (subjective and objective memory impairment and no dementia) as well as by the inclusion and exclusion criteria (evidence of any neurologic or other medical disorder that could produce cognitive deterioration) for the total study population, for both sexes, and for four age groups (60 to 64, 65 to 69, 70 to 74, and 75 to 78 years). Subjective memory impairment was present in 76.3% of the subjects. Prevalence rates for objective memory impairment ranged from 31.9 to 78.4% in individual tests. A total of 564 subjects (239 men, 325 women) were classified as having AAMI by the inclusion criteria alone, giving a prevalence rate of 53.8% (men, 57.4%; women, 51.3%). When we included the exclusion criteria, the prevalence of AAMI decreased to 38.4% (men, 42.5%; women, 35.7%). By both methods, age- and sex-specific prevalence rates were highest in the youngest group, aged 60 to 64 years, and lowest in the oldest group, aged 75 to 78 years. We conclude that the prevalence of AAMI, by the diagnostic criteria of the NIMH Work Group, is high in the elderly Finnish population.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of slow brain potentials by working memory load in spatial and nonspatial auditory tasks.

Slow event-related brain potentials were recorded from the human scalp during spatial and nonspatial auditory delayed matching-to-sample and n-back tasks to find out whether there are differences in the distribution of slow potentials during the retention of audiospatial and pitch information. The performance of both the location and pitch tasks produced slow potentials during the delay phase of the memory tasks. The delay-related slow potential was modulated by the amount of information to be processed during the tasks at the parietal-occipital sites. The distribution of mnemonic modulation was, however, not different between the tasks. The results suggest that there is integration of auditory information processing in the neuronal networks engaged in mnemonic processing of pitch and location.

Slowing of electroencephalogram and choline acetyltransferase activity in post mortem frontal cortex in definite Alzheimer's disease.

Twenty-five (96%) of 26 patients with histologically verified moderate to severe Alzheimer's disease had abnormal electroencephalograms. The patients with the slowest (5-6 Hz) dominant occipital rhythms had significantly lower choline acetyltransferase activity in the post mortem frontal cortex than the patients with highest rhythm (8-9 Hz) (analysis of covariance adjusted for the neuropsychological test score). Concentrations of dopamine, noradrenaline or serotonin in the frontal cortex did not differ in the patient groups with the slowest and highest rhythms. Neither did scores of senile plaques or neurofibrillary tangles differ between these groups. In Alzheimer patients, the frequency of the dominant occipital rhythm correlated with the total score of the neuropsychological test (r = 0.58, P less than 0.01) and with the subscales of praxic functions and expressive speech, memory and general reasoning. The results suggest that the cholinergic deficit may contribute to the slowing of the electroencephalogram found in patients with Alzheimer's disease.

Histamine neurons in human hypothalamus: anatomy in normal and Alzheimer diseased brains.

The anatomy of histamine-immunoreactive cell bodies in normal adult human brain was examined in detail. In addition, the distribution of these cells in three cases of Alzheimer's disease was compared to the distribution of neurofibrillary tangles. Histamine-immunoreactive cell bodies were confined to the tuberal and posterior hypothalamus, forming the tuberomammillary nuclear complex. Most of the about 64,000 histamine neurons were large and multipolar. They comprised four distinct parts: (i) a major ventral part corresponding to the classical tuberomammillary nucleus, (ii) a medial part including the supramammillary nucleus and part of the posterior hypothalamic area, (iii) a caudal paramammillary part, and (iv) a minor lateral part. The parts showed some similarity with the subgroups in rat. In human, as compared to rat, the histamine neurons occupy a larger proportion of the hypothalamus. Numerous neurofibrillary tangles were found in the Alzheimer hypothalami, concentrated in the tuberomammillary area. Most of them were of globular type and extracellular, and only a minority were histamine immunoreactive. They may represent remnants of degenerated tuberomammillary neurons.

A rapid dosimetric method with controlled tidal breathing for histamine challenge. Repeatability and distribution of bronchial reactivity in a clinical material.

A rapid dosimetric method with controlled tidal breathing for histamine challenge was evaluated by assessment of its repeatability, by comparing to a present nondosimetric standard method, and by application to adult patients with recent asthma (n = 31), chronic asthma (n = 33), chronic cough (n = 71) or chronic rhinitis (n = 41) and to healthy controls (n = 31). An automatic inhalation-synchronized dosimetric jet nebulizer with a known lung deposition of the aerosol was used to administer histamine and to control breathing. The non-cumulative doses of histamine diphosphate were 0.025, 0.1, 0.4 and 1.6 mg, administered during 0.4 s following tidal inspiration of 100 ml of air. The test procedure required 1 inhalation of histamine 4 mg/ml and followed by 1, 4 and 16 inhalations of histamine 16 mg/ml from the device, and its duration was about 30 minutes. The intraindividual correlation coefficient of the histamine dose causing a reduction of 15 percent in FEV1 (PD15FEV1) on 2 consecutive days in 14 asthmatic subjects was 0.937; the standard error of the single determination was 13 percent of the mean PD15 FEV1. A PD15FEV1 value below 0.4 mg was found only in asthmatic subjects; in chronic asthma, below 0.5 mg; in recent asthma, between 0.1 mg and 1.6 mg or more. In patients with chronic cough and chronic rhinitis, 20 and 32 percent, respectively, the PD15FEV1 values between 0.4 and 1.6 mg, the other patients in these groups were non-responsive. In all healthy control subjects, the PD15FEV1 was over 1.0 mg, 80 percent of them were nonresponsive to the maximum 1.6 mg dose. This new test allows rapid, accurate, and quantitative assessment of bronchial responsiveness to histamine.

A follow-up study of age-associated memory impairment: neuropsychological predictors of dementia.

OBJECTIVE: To examine the clinical course of age-associated memory impairment (AAMI) and to evaluate the value of neuropsychological tests in predicting cognitive decline in AAMI subjects in a follow-up period of more than 3 years. DESIGN: Prospective cohort study. SETTING: The outpatient Memory Research Unit of the Department of Neurology at the University of Kuopio in Eastern Finland. PARTICIPANTS: A sample of 229 subjects (mean age 71.7 years) identified in two screening studies as having AAMI. MEASUREMENTS: A battery of neuropsychological tests and a structured inquiry for health status and subjective memory complaints were performed at baseline and follow-up to diagnose AAMI according to the criteria proposed by a National Institute of Mental Health work group. RESULTS: Of the 229 subjects, 176 (76.9%) participated in the follow-up for, on average, 3.6 years after the baseline. Of the participants, 104 (59.1%) still met the AAMI criteria. Other subjects were classified into five subgroups: (1) subjects showing decline in cognition meeting dementia diagnosis (16, 9.1% (13 of them AD)); (2) subjects with mild cognitive decline meeting neither dementia nor AAMI criteria (13, 7.4%); (3) subjects with memory performance now superior to AAMI criteria (17, 9.7%); (4) subjects having a disease classified as exclusion in the criteria (15, 8.5%); (5) subjects not now reporting subjective memory loss in everyday life (9, 5.1%). Two subjects (1.1%) were not classified because of incomplete data. Neuropsychological tests predicted which subjects would develop dementia during the follow-up period. The best discriminators between these subjects and those who remained AAMI were memory and verbal fluency tests. CONCLUSION: The study suggests that, in general, AAMI is nonprogressive, but the AAMI population also includes subjects with early dementia and subjects without genuine memory loss. However, these subjects can be differentiated with a more detailed neuropsychological evaluation.

Subjective memory complaints and personality traits in normal elderly subjects.

OBJECTIVE: To evaluate the relationship between objectively measured memory functions and subjective complaints of memory disturbance and whether subjective complaints are affected by some personality traits or affective states. DESIGN: Cross-sectional two-group comparison. SETTING: The city of Kuopio in Eastern Finland, considered representative of the urban elderly population of Finland. PARTICIPANTS: Originally 403 subjects aged 67-78 years from the random sample and then two matched study groups initially including eighteen subjects but only ten in the final analysis. MEASUREMENTS: Screening and follow-up examinations of subjects with and without subjective memory complaints: (1) Memory functions: Benton's visual retention test and the paired-associated learning subtest of Wechsler Memory Scale. (2) Memory complaints: Memory Complaint Questionnaire. (3) Personality traits and affective state: Two subscales from Minnesota Multiphasic Personality Inventory and Geriatric Depression Scale. RESULTS: Complaints of memory loss did not correlate with the actual memory performance in the tests. However, those subjects who most emphatically complained of memory disturbance had greater tendencies toward somatic complaining, higher feelings of anxiety about their physical health, and more negative feelings of their own competence and capabilities than those who did not complain of memory deterioration associated with aging. CONCLUSIONS: The study suggests that subjective feelings of memory impairment are more closely associated with personality traits than with actual memory performance in normal elderly people.

Selective tuning of the left and right auditory cortices during spatially directed attention.

Effects of spatially directed auditory attention on human brain activity, as indicated by changes in regional cerebral blood flow (rCBF), were measured with positron emission tomography (PET). Subjects attended to left-ear tones, right-ear tones, or foveal visual stimuli presented at rapid rates in three concurrent stimulus sequences. It was found that attending selectively to the right-ear input activated the auditory cortex predominantly in the left hemisphere and vice versa. This selective tuning of the left and right auditory cortices according to the direction of attention was presumably controlled by executive attention mechanisms of the frontal cortex, where enhanced activation during auditory attention was also observed.

Temporal window of integration revealed by MMN to sound omission.

The central auditory system for event perception involves the integrating mechanism of sequential information addressed by the present study. The mismatch negativity (MMN) component of the event-related potentials (ERP) reflects the automatic detection of sound change. ERPs to occasionally omitted stimuli were measured when sequences with constant stimulus onset asynchronies (SOAs) were presented. In separate blocks, the SOA was from 100 to 350 ms. A clear MMN was elicited by a stimulus omission in a sequence of regularly spaced tone pips only when the SOA was shorter than 150 ms, yielding an estimate for the duration of the temporal window of integration used the perceptual segregation of auditory events.

Auditory sensory memory impairment in Alzheimer's disease: an event-related potential study.

Auditory event-related potentials (ERP) were recorded from 10 healthy older subjects and 9 patients with Alzheimer's disease (AD) to investigate whether auditory sensory memory is impaired in AD. Standard (85%) and deviant (15%) tones were presented in random order with interstimulus intervals (ISI) of 1 s or 3 s in separate blocks. Deviant tones elicited a specific ERP component called mismatch negativity (MMN) which reflects automatic stimulus change detection and thus presumably, the neural basis of sensory memory in audition. The MMN amplitude decreased as a function of the ISI more in the AD group than in the control group. This suggests that the memory trace decays faster in the AD patients than in age-matched healthy controls.

Event-related potentials reveal a memory trace for temporal features.

Auditory event-related potentials (ERPs) were recorded from reading subjects while they were presented with 50 ms tone pips intervened by regular silent intervals of 550 ms. This interval was occasionally shortened either to 250, 100, 25, 10, or 2 ms, which resulted in the elicitation of the mismatch-negativity (MMN), a change-specific ERP component not elicited by tones appearing after the regular, longer intervals. This indicates that the MMN is not just due to new afferent elements activated by deviant but not standard stimuli. In addition, the present results suggest that the temporal parameters of acoustic stimulation are also encoded in memory traces which therefore are representations of auditory events rather than only of static stimulus aspects.

Visuospatial mnemonic load modulates event-related slow potentials.

Electroencephalographic slow wave potentials were recorded during the performance of visuospatial working memory tasks. The aim was to study the effects of varying mnemonic loads on slow potentials, and to dissociate the contribution of mnemonic and motor components. Subjects were tested with three spatial delayed matching-to-sample tasks in which the mnemonic load varied while the preparatory motor demands remained constant. The delay-related slow potential was more negative during the tasks in which the subjects had to memorize the locations of six or four stimuli than when only one location had to be memorized. Significant differences between the slow potentials in the tasks with different mnemonic loads were recorded at frontal and temporal recording sites. Since the preparatory motor requirements were similar in all tasks, the modulation of slow potentials reflects working memory processing rather than motor preparatory activity.

Selegiline treatment facilitates recovery after stroke.

OBJECTIVE: Selegiline (L-deprenyl) is a selective monoamine oxidase B (MAO-B) inhibitor used in the treatment of Parkinson's disease. In addition, it is thought to rescue neurons with a loss of target-derived trophic support. Several mechanisms have been proposed to explain these phenomena, such as the production of neurotrophic actions through astrocyte activation, reduction of free radical production, or the presence of antiapoptotic properties. The aim of this study was to investigate whether the systemic administration of selegiline facilitates recovery after a cerebral infarction in humans. METHODS: This phase II study was randomized, double-blind, and placebo controlled. Selegiline, 5 mg, or matched placebo was given twice a day for 3 months. The drug therapy was started within 48 h after a hemispheric infarction in the territory of middle cerebral artery. There were 24 patients recruited. Twenty patients were followed up to 3 months or until their death, and they represent the efficacy analysis group. The primary efficacy parameters were Scandinavian Stroke Scale (SSS), Barthel Index (BI), and Fugl-Meyer Scale (FMS). Secondary parameters were Zung Self-Rating Depression Scale (ZDS) and 15-Dimensional Measure of Health Related Quality of Life test (15-D). RESULTS: SSS improved statistically significantly from the baseline when compared with placebo (p = 0.019). The results were parallel among the other two primary efficacy variables (BI and FMS), showing a positive trend for selegiline, although they did not reach statistical significance. Similarly, in the analysis of the secondary efficacy variables, both the 15-D test and ZDS supported this positive trend in favor of selegiline, although no statistically significant differences between groups were found (p = 0.06 in 15-D test). CONCLUSIONS: Selegiline seems to be beneficial after a cerebral infarction. This benefit may be due to the enhancement of the recovery process.

The activation of unmyelinated or myelinated afferent fibers by brief infrared laser pulses varies with skin type.

Brief infrared laser pulses were applied to 3 different skin areas in man. Reaction times indicated that A delta-fibers were activated in the dorsal and volar skin of the finger whereas only C-fibers were activated in the hairy skin of the forearm. The qualitative sensations were in line with this interpretation. We conclude that the activation of unmyelinated or myelinated afferent fiber populations with brief laser pulses varies with skin type.

Decreased somatostatin-like immunoreactivity in cerebral cortex and cerebrospinal fluid in Alzheimer's disease.

To investigate changes in the somatostatinergic neurons of patients with Alzheimer's disease (AD), we determined the somatostatin-like immunoreactivity (SLI) in post-mortem brain tissue of histopathologically confirmed AD patients and in CSF of probable AD patients (according to DSM III). The CSF values were then correlated with psychological test scores. In 6 AD patients the SLI values were decreased 42% (P less than 0.005) in the frontal cortex, 28% (P less than 0.05) in the temporal cortex and 42% (P less than 0.01) in the parietal cortex but not in the thalamus and putamen compared to 11 control patients. In some brain areas there were statistical correlations between SLI values and cholinergic markers, choline acetyltransferase and acetylcholine esterase activities, suggesting a relationship between these two neurotransmitter systems. In the CSF among 75 AD patients SLI was 35% lower (P less than 0.001) than in controls. Severely demented power (P less than 0.001) than in controls. Severely demented patients showed lower SLI values than moderately demented individuals, but this difference was not significant. There was a weak but statistically significant correlation between SLI values in CSF and neuropsychological test scores. This study further confirms the involvement of somatostatinergic neurons in AD and suggests that this involvement may be related to the progression of dementia symptoms.

Do event-related potentials to infrequent decrements in duration of auditory stimuli demonstrate a memory trace in man?

Sequences of identical acoustic stimuli were presented to normal subjects reading a book while event-related brain potentials (ERP) elicited by these stimuli were recorded. Occasional irrelevant decreases and increases in stimulus duration elicited an ERP component called the mismatch negativity (MMN). This component was larger over the right hemisphere irrespective of the ear stimulated. These data implicate memory representations which develop automatically and represent the physical features of the repetitive stimulus accurately. Further, when an input does not match with such a trace the MMN is generated. The memory traces involved appear to be those of the acoustic sensory memory, the 'echoic' memory.

2',3'-cyclic nucleotide-3'-phosphodiesterase activity as an index of myelin in the post-mortem brains of patients with Alzheimer's disease.

The activity of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) was determined as an index of myelin in the post-mortem brain samples of 16 patients with Alzheimer's disease (AD) and of 14 controls. The CNPase activity was mildly increased in the temporal, hippocampal and parietal cortex in AD subjects pointing to a relative sparing of myelin as compared to the neuron loss within cortex in AD. In the hippocampus the CNPase activity was decreased in AD patients indicating loss of myelin and thus myelinated axons in this area in AD.