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Functional MR imaging in Alzheimer's disease during memory encoding.

BACKGROUND AND PURPOSE: We applied functional MR imaging with a learning task in healthy elderly volunteers and in patients with Alzheimer's disease to study brain activation during memory performance. The purpose was to determine the feasibility of functional MR imaging during a learning task in healthy elderly volunteers and in patients with Alzheimer's disease and to test our hypothesis that brain activation is decreased in the medial temporal lobe (MTL) memory system in patients with Alzheimer's disease compared with control volunteers. METHODS: In 12 patients with mild to moderate forms of Alzheimer's disease and 10 elderly control volunteers, activation of the MTL memory system was studied. We used two learning tasks that required the encoding of new information into memory. After the functional MR imaging experiment, participants were tested for recognition of the encoded objects. RESULTS: In the elderly control volunteers, activation during memory encoding was observed in medial and lateral temporal lobe structures (fusiform, parietal and occipital parts, and hippocampal formation) and in the frontal cortex, as reported previously in studies of young control volunteers. Focusing on the MTL, we observed that activation was significantly decreased in patients with Alzheimer's disease compared with control volunteers in the left hippocampus and parahippocampal gyrus bilaterally during the first encoding task but not during the second (P < .05, uncorrected). CONCLUSION: Functional MR imaging with a learning task seems feasible in elderly volunteers and in patients with Alzheimer's disease. The measured functional signal decrease in MTL areas warrants further exploration of the (early) diagnostic usefulness of functional MR imaging in cases of Alzheimer's disease and other dementias.

Aged↗

[Amnesia following herpes simplex encephalitis].

We describe three patients presenting themselves with amnesia following herpes simplex encephalitis. All three patients showed anterograde amnesia. Moreover, one patient showed retrograde amnesia extending about fifty years prior to the onset of the illness. Two patients revealed semantic memory disorder, disinhibitory behaviors and confabulations, which suggested the existence of frontal lobe dysfunction. MRI of all three patients disclosed uni- or bilateral temporal lesions. SPECT images showed decreased uptake not only in the temporal lobes but also in the frontal lobes. Amnesia following herpes simplex encephalitis has been thought to be caused by the temporal lobe disorder. However, we postulate that the frontal lobe dysfunction might contribute to the appearance of amnesia.

Aged↗

Relationship between linguistic performance and memory deficits in retarded children.

Performance of retarded children was measured on four tests of linguistic ability and two memory tests. Subjects were 50 retarded children: 10 each at mental ages 3, 4, 5, 6, and 7. The relationship between linguistic performance and memory was assessed by correlational analysis. Multiple and partial correlations were computed using a measure of language comprehension and a measure of memory span as predictor variables and three measures of language production as criterion variables. Different patterns of correlation were found with the three production as criterion variables. Different patterns of correlation were found with the three production measures, suggesting that the relative importance of memory span in language production depends on the specific production task.

Auditory Perception↗

Lateralized cortical perfusion in women with Alzheimer's disease.

OBJECTIVE: To define the pathophysiologic substrate of gender differences in cognition and behavior in Alzheimer's disease (AD). DESIGN: Hemispheric regional cerebral blood flow (rCBF) was studied in a consecutive series of dementia patients using single photon emission computed tomography (SPECT). PARTICIPANTS: Subjects included 300 outpatients who were studied with SPECT as part of a diagnostic evaluation for degenerative dementia or memory disorder. METHOD: Based on qualitative descriptions by a radiologist, subjects were classified as having unilateral left, unilateral right, bilateral, or no perfusion defects. Semiquantitative analysis of SPECT images was also performed using region of interest radionuclide counts normalized to the cerebellum. RESULTS: Among 174 females and 126 males, unilateral left hemisphere defects were found more commonly in women than men (24% vs 10%; chi 2 = 9.4; P = .009). This observation was most significant for the 103 females and 62 males regarded as having probable AD (26% vs 8%; chi 2 = 9.3; P = .01). In a multiple regression model of clinical variables, shorter duration of disease and female gender were significant independent predictors of the unilateral left hemisphere pattern among those with probable AD. Age, family history, education, handedness, and severity of cognitive impairment were not significant contributors. CONCLUSIONS: Women with AD exhibit greater heterogeneity in rCBF than men. Asymmetry in rCBF occurs more often in women. In some cases, this is related to relative preservation of right hemisphere function in women.

Aged↗

Saccadic hypometria in drug-naive and drug-treated schizophrenic patients: a working memory deficit?

In certain conditions patients with schizophrenia make markedly smaller (hypometric) saccades than controls. This hypometria has been thought to reflect dopaminergic blockade as a result of antipsychotic medication. We tested this hypothesis by comparing the performance of an antipsychotic-naïve group and an antipsychotic-treated group of first-episode schizophrenic patients on a predictive saccade paradigm. We explored the possibility that hypometria reflects a spatial working memory deficit by correlating performance on neuropsychological tests of mnemonic function with saccadic accuracy. Both the drug-naïve and treated schizophrenic patients made hypometric saccades when compared with a group of matched controls. Primary saccade amplitude also correlated significantly with performance on some of the neuropsychological tests. These results are discussed in terms of the roles of cortical dopamine and working memory deficits in schizophrenic patients.

Adult↗

Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits.

We injected a combination of the beta-amyloids (Abetas) Abeta40 and Abeta43 to "seed" formation of amyloid deposits in the dorsal dentate gyrus of rats in vivo, on the basis of a theory of Jarrett and Landsbury (1993). Rats were tested on several different learning tasks, and synaptic transmission and plasticity were assessed in vivo. Between 7 and 16 weeks after injection, we found aggregated amyloid material, reactive astrocytosis, microgliosis, and cell loss around the sites of injection. Rats were impaired specifically in working memory type tasks in accordance with the type of memory deficit observed in the early stages of Alzheimer's disease. Synaptic transmission and long-term potentiation, a candidate cellular mechanism for memory, were severely impaired in vivo. Injections of the same dose of fragments individually did not induce these effects. These findings suggest that aggregated amyloid material induces cognitive deficits similar to those observed in the early phases of Alzheimer's disease via an alteration in neuronal transmission and plasticity.

Alzheimer Disease↗

[High mental functions in healthy individuals and in cerebrovascular diseases].

A knowledge of time parameters of the high mental functions of the brain under normal and pathological conditions may serve as a key to understanding of their intimate mechanisms. During the first stage of the study a set of different tests including "word association", "paired words learning" was used to compare these indices in patients with atherosclerotic discirculatory encephalopathy and in normal individuals. The dynamics and volume of the short-term memory and processes of attention were evaluated. An increase of the response latencies in the paired words' tests and a decrease of both volume of short-term memory and the processes of attention were identified. Application of the tests with semantically similar or unlike words was informative.

Adult↗

[Comparative analysis of memory pathologies of various genesis: epileptic patients and Chernobyl nuclear plant accident liquidators].

Different types of short-term memory were examined in two groups of people: epileptic patients during remission and participants of cleaning after the incident at Chernobyl nuclear power plant. The control group matched the experimental groups by sex, age, and education. It was found that memory dysfunctions were similar independently of the kind of pathology. The associative memory was most vulnerable. This finding is explained in terms of the role of protein-nucleic synthesis (the molecular-universal aspect) in the formation of human and animal associative memory.

Adolescent↗

[Cognitive deterioration in Parkinson's disease].

INTRODUCTION: Whether there are mental changes in Parkinson s disease (EP) or not, has been a confused and contradictory subject since the earliest studies and semiological definition of the disorder. James Parkinson himself, in his study An essay on the shaking palsy (1817), stated that in the condition he described, the sense and intellect were not damaged. DEVELOPMENT: Thanks to the development of cognitive neuropsychology, at the present time there are rather more precise concepts regarding this fascinating area of neurology. We give a summary, as schematic as possible, of theory relating to the known data. 1. The presence or absence of cognitive deterioration in EP 2. The neuropsychological characteristics of cognitive involvement in EP, cognitive defects in incipient EP and in established EP. 3. The risk factor involved in the occurrence of cognitive deterioration. CONCLUSIONS: This knowledge should be used for better understanding of the patient s mental state at every stage of the disease, during follow up studies and for the neuro conductual therapeutic and socio familial approach in each case.

Adaptation, Psychological↗

[Rivastigmine for Alzheimer disease; evaluation of preliminary results and of structured assessment of efficacy].

OBJECTIVE: Evaluation of the initial experiences with rivastigmine in Alzheimer's disease. DESIGN: Retrospective. METHOD: Data were collected from patients with Alzheimer's disease who were treated with rivastigmine between 1 October 1998-30 November 1999 at the Memory Disorders Outpatients Clinic at the Academic Medical Centre or the Slotervaart Hospital, both in Amsterdam, the Netherlands. Before, and 6 months after treatment, the course of the disease was evaluated using clinimetric scales relating to cognitive functions, behavioural abnormalities and instrumental daily functions. The treatment results were considered to be 'favourable' if they corresponded with a disease course seen in less than 10% of untreated Alzheimer patients. RESULTS: During the study period, 53 patients were treated, 36 women and 17 men, with a mean age of 77 years (range: 57-89). Follow-up data were incomplete for four patients. Of the remaining patients, 27 (55%; 95% CI: 40-69) withdrew from treatment during the first 6 months, mainly because of gastrointestinal side-effects. Of the other 22 patients (45%; 31-60) 18 continued with rivastigmine treatment (18/49 = 37%; 23-52), and in three of these patients the disease course was favourable (3/49 = 6%; 1-17). CONCLUSION: In daily practice, over 50% of the patients were unable to tolerate rivastigmine. Structured evaluation of treatment efficacy was feasible in this population. Treatment with rivastigmine seemed to be beneficial in a small proportion of the patients.

Activities of Daily Living↗

[Vascular dementia and systemic changes].

The aim of the study was to evaluate risk factors of atherosclerosis and extra-cerebral target organ damage in patients with hypertension and vascular based mild memory disorders. A group of the study included 20 persons at age of 54-75 (8 males and 12 females) with mild vascular dementia (20-25 pts in MMSE, 22.8 +/- 1.73) with treated mild hypertension. A diagnosis of vascular dementia was confirmed in MRI by two independent experts. All examined patients presented multiinfarction changes in central nervous system as a cause of dementia. The study protocol contained present history, physical examination, 24-hour ambulatory blood pressure monitoring (ABPM), ECG, biochemical tests: total cholesterol, HDL-Ch, LDL-Ch, triglycerides, glucose, urea, creatinine plasma levels and urine test for microalbuminuria. In part of the study group (55%) echocardiography with posterior wall (PW) thickness and ejection fraction (EF) evaluation was performed. In the analysed group mean 24-hour blood pressure values were not elevated (SBP 130.8 +/- 15.8 mm Hg and DBP 77.6 +/- 9.2 mm Hg at day, respectively 121.6 +/- 17.1 mm Hg and 68.2 +/- 11.6 mm Hg at night). No significant (> 10%) nocturnal SBP decrease was observed, however DBP fall was noticed. Either total cholesterol (n < 5.2 mmol/l) or LDL-Ch (n < 3.5 mmol/l) plasma levels were increased in patients with vascular dementia and ranged respectively 5.8 +/- 0.9 and 3.7 +/- 0.9 mmol/l, HDL-Ch and triglycerides levels remained normal (respectively 1.7 +/- 0.5 and 1.5 +/- 1.1 mmol/l). Mean urea and creatinine levels were maintained in normal range (urea 5.8 +/- 1.7 mmol/l, creatinine 75.5 +/- 15.1 mumol/l). In a part of study group (35%) microalbuminuria was presented (urine albumine > 20 mg/l). In majority of patients with hypertension and vascular dementia a few risk factors co-existed. No systolic blood pressure decrease observed at night in 24-hour blood pressure monitoring, though normal mean values, can play an important role in vascular abnormalities progression.

Aged↗

Nonspatial and subdivision-specific working memory deficits after selective lesions of the avian prefrontal cortex.

Association areas in the avian forebrain are shown to subserve higher cognitive functions, including working memory. One of these areas, the neostriatum caudolaterale (NCL) of pigeons, has been functionally compared with the mammalian prefrontal cortex (PFC) because of its prominent role in spatial delay and reversal tasks and its innervation by the dopaminergic system that modulates these functions. However, whereas the PFC maintains in working memory information of different domains, the essential role of the NCL in working memory has been demonstrated only for spatial tasks. To investigate whether the avian NCL is also crucial for nonspatial working memory functions, pigeons were tested in an object-related (color) delayed matching-to-sample (DMTS) task. Bilateral lesions were placed in the entire, dorsal, or ventral NCL to test for possible functional subdivisions that were proposed to exist on the basis of neurochemical and behavioral data. Pigeons with total, dorsal, and ventral NCL lesions showed significant deficits in their DMTS performance, whereas controls were not impaired. Thus, the avian NCL is critically involved in nonspatial working memory processes. Recovery from performance deficits was observed in animals with ventral or total NCL lesions, whereas animals with dorsal NCL lesions showed no improvement. Ventral NCL may mediate perseverative behavior, whereas dorsal NCL might be involved in active working memory. Differences in the connections of these subdivisions with striatal areas and other association areas in the frontomedial forebrain underline functional differences. The data indicate a possible segregation of functions in the avian NCL.

Animals↗

[Therapeutic potential of protein kinase CK2 modulators].

Data on the nuclear cascade of signal transduction, including protein kinase CK2 (PKCK2), transcription factor HMG14 and chromatin myosin-like proteins, are generalized with regard for the modern understanding of mechanisms of synaptic plasticity. The role of the neurospecific isoform and subunit structure of PKCK2, of the individual subunit autophosphorylation of PKCK2, of phosphorylation of substrate-proteins in the enzyme activity and of conformation transformations of chromatin is examined. Data on changes in the CK2-induced cascade and synaptic plasticity in learning, on age-related amnesia and on cognitive deficits induced by ethanol and chloridine in rat embryos are presented. The prospects for using modulators PKCK2, 4,5-di(N-methylcarbamoyl)-l-alkyl-imidazoles, as potential nootropics are discussed.

Animals↗

[Acetylcholinesterase inhibitors--beyond Alzheimer's disease].

Based on a literature review, the application of Acetylcholinesterase inhibitors, IAchE (donepezil, rivastigmine, galantanine) in the treatment of various illnesses which have cholinergic system disability and dementia in their course--(dementia with Lewy bodies, vascular dementia, Parkinson's disease, Multiple Sclerosis, Down Syndrome), delirium symptoms (e.g. Korsakoff psychosis), hyperkinesis, attention and memory disorders--is presented. Promising results in the treatment of late dyskinesias, in schizophrenia with impaired cognitive function, as well as in the additional treatment of various psychotic states are noted. It should be stressed that in Poland, the IAchE have been approved only in the treatment of slight to moderate dementia in the course of Alzheimer's disease.

Alzheimer Disease↗

Effects of vinconate on scopolamine-induced memory impairment in rhesus monkeys.

Effects of vinconate on specifically impaired short-term memory were studied in rhesus monkeys. Monkeys were trained to perform for orange juice reinforcement under a matching-to-sample response procedure. In the procedure, monkeys had to choose one of two stimuli that had the same color as the sample stimulus. Half of a daily session consisted of simultaneous trials where the sample stimulus was present during the time of choice. The other half of the session consisted of delayed trials where the sample stimulus had been presented but withheld at the time of choice. After the repeated training, the matching-to-sample responses were established with the percentage of correct choice responses (CR%) in both types of trials exceeding 90%. The doses of scopolamine, intervals between administration of this drug and the start of test session, and delay times in delayed trials were adjusted from one monkey to another so that delayed matching-to-sample responses were impaired by scopolamine while simultaneous matching-to-sample responses were less impaired by this drug. Scopolamine (32 or 45 micrograms/kg, s.c.) decreased the CR% for delayed trials more markedly than the CR% for simultaneous trials in four monkeys. Intragastrically administered vinconate at 16 mg/kg attenuated the scopolamine-induced short-term memory impairment. These results suggested that vinconate possesses specific ameliorating action on memory impairment caused by hypofunction of the cholinergic system in the brain.

Acetylcholine↗

A within-subjects, within-task demonstration of intact spatial reference memory and impaired spatial working memory in glutamate receptor-A-deficient mice.

Gene-targeted mice lacking the AMPA receptor subunit glutamate receptor-A (GluRA) (GluR1) and wild-type controls were compared on a radial-maze task in which the same three of six arms were always baited, but in which the rewards of milk were not replaced within a trial. This procedure allowed not only a within-subjects but also a within-trials assessment of both spatial working memory (WM) and reference memory (RM) in GluRA-/- mice, using identical spatial cues. In experiment 1, the GluRA-/- mice made more WM and RM errors during task acquisition. However, separate groups of GluRA-/- and wild-type mice (experiment 2) acquired a purely RM version of the task at a similar rate, using a paradigm with which it was not possible to make WM errors (doors prevented mice from re-entering an arm that they had already visited on that trial). In contrast, mice with hippocampal lesions were dramatically impaired. These results are consistent with the possibility that the WM impairment in the GluRA-/- mice during experiment 1 produced interference that disrupted RM acquisition. A WM component was therefore introduced after RM acquisition in experiment 2 (i.e., the mice were no longer prevented from re-entering a previously visited arm). The GluRA-/- mice now made considerably more WM errors than did wild-type mice, but simultaneously, RM was only mildly and transiently impaired. These experiments provide additional evidence of a selective spatial WM deficit coexisting with intact spatial RM acquisition in GluRA-/- mice, suggesting that different neuronal mechanisms within the hippocampus may support these different kinds of information processing.

Animals↗