Functional MR imaging in Alzheimer's disease during memory encoding.
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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. (+info)
A nucleoside-nucleotide mixture may reduce memory deterioration in old senescence-accelerated mice.
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We investigated the effects of a mixture of dietary nucleosides and nucleotides (NS + NT) on memory in 1- and 7-mo-old senescence-accelerated mice (SAM). Memory retention was studied with passive avoidance (step-through) and active avoidance (shuttle) tests. For 14 wk, mice in the control groups were fed a 20 g of casein/100 g diet, whereas the NS + NT groups were fed this diet supplemented with a 0.5 g of NS + NT mixture/100 g. All mice were killed at wk 14, and we studied the brain histopathology. Lipofuscin, monovacuoles and multiple vacuoles of various brain regions were measured. Body weight, food intake and ambulatory activity did not differ between the control and NS + NT groups. In old mice, the time of passive avoidance was significantly higher in the NS + NT group than in the control group at d 1 and 7 (P: < 0.05). However, such an effect of NS + NT was not observed in young mice. In the active avoidance test, the incidence of successful avoidance in old mice was higher in the NS + NT group than in the control group at d 1 and 2 (P: < 0.05). The percentages of specific brain cells containing lipofuscin were lower in NS + NT groups than in the control groups in both young and old mice (P: < 0.05). The number of monovacuoles and multiple vacuoles in specific brain regions tended to be lower (P: = 0.1-0.25) in NS + NT than in control groups, with significant differences in the microvacuoles of the middle cortex of young mice and in the multiple vacuoles in the hind cortex of old mice (P: < 0. 05). These results suggest that increased dietary NS + NT may be associated with decreases in the age-induced deterioration of brain morphology and certain memory tasks. (+info)
Impact of emotion on memory. Controlled study of the influence of emotionally charged material on declarative memory in Alzheimer's disease.
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BACKGROUND: In an earlier study we showed that a powerful emotional experience (the Kobe earthquake) reinforced memory retention in patients with Alzheimer's disease, but we could not control factors other than the emotional impact of the earthquake. AIMS: To test our previous findings in a controlled experimental study. METHOD: Recall tests consisting of two short stories were administered to 34 patients with Alzheimer's disease and 10 normal subjects. The two stories were identical except for one passage in each story: one was emotionally charged (arousing story) and the other (neutral story) was not. RESULTS: In both groups, the emotionally charged passage in the arousing story was remembered better than the counterpart in the neutral story. In addition, the extent of the memory improvement was similar in the subjects and in the controls. CONCLUSIONS: The results provide further evidence that emotional arousal enhances declarative memory in patients with Alzheimer's disease, and give a clue to the management of people with dementia. (+info)
The scopolamine-induced impairment of spatial cognition parallels the acetylcholine release in the ventral hippocampus in rats.
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We investigated the relationship between the induction of spatial cognition impairment in the 8-arm radial maze task and regional changes (ventral hippocampus (VH), dorsal hippocampus, frontal cortex, and basolateral amygdala nucleus) in brain acetylcholine (ACh) release using microdialysis in rats treated with muscarinic (M) receptor antagonists. In a behavioral study, two M1 antagonists, scopolamine (0.5 mg/kg, i.p. and 20 microg, i.c.v.) and pirenzepine (80 microg, i.c.v.), but not an M2 antagonist, AF-DX116 (40-80 microg, i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain microdialysis with Ringer's solution containing 0.1 mM eserine sulfate, scopolamine and AF-DX116, but not pirenzepine, increased ACh release in the VH. Moreover, in the bilateral injection of scopolamine (2 microg/side), the VH and dorsomedial thalamus nucleus were important regions for scopolamine-induced impairment of spatial cognition. A simultaneous determination of the behavioral changes revealed that scopolamine (0.5 mg/kg, i.p.) markedly decreased the ACh contents and also increased the ACh release in all regions tested. Especially, the changes in the ACh release of the VH closely paralleled the induction of the scopolamine-induced impairment of spatial cognition. These results suggest that the blocking balance between M1 and M2 muscarinic receptor in the VH therefore plays a major role in the spatial cognition impairment induced by scopolamine in the 8-arm radial maze task. (+info)
Stability of the preclinical episodic memory deficit in Alzheimer's disease.
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We sought to determine the course of the preclinical episodic memory deficit in Alzheimer's disease. Using data from a population-based study, we compared persons who developed Alzheimer's disease n = 15) with persons who were non-demented n = 105) 6 and 3 years prior to the diagnosis of dementia. Participants were tested on tasks assessing episodic memory free recall and recognition of words) and short-term memory digit span). The incident Alzheimer's disease cases performed more poorly than their non-demented counterparts both 3 and 6 years before diagnosis on recall and recognition. There were no group differences in either forward or backward digit span. The selective impairment of episodic memory before the diagnosis of Alzheimer's disease is consistent with the view that early changes in the hippocampal complex play an important role in the memory deficit in preclinical Alzheimer's disease. On both preclinical measurement occasions, recall and recognition made independent contributions to group classification in logistic regression analyses. However, there was no evidence for accelerated decline of episodic memory in the incident Alzheimer's disease group from 6 to 3 years before diagnosis. These results indicate that Alzheimer's disease is characterized by a long preclinical period during which episodic memory deficits are detectable. The magnitude of these deficits appears to be quite stable, at least up to 3 years before diagnosis. This may reflect the fact that those biological events that eventually result in clinically diagnosed Alzheimer's disease e.g. the appearance of amyloid plaques and neurofibrillary tangles) accumulate at a relatively slow rate. (+info)
Retrograde amnesia for spatial memory induced by NMDA receptor-mediated long-term potentiation.
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If information is stored as distributed patterns of synaptic weights in the hippocampal formation, retention should be vulnerable to electrically induced long-term potentiation (LTP) of hippocampal synapses after learning. This prediction was tested by training animals in a spatial water maze task and then delivering bursts of high-frequency (HF) or control stimulation to the perforant path in the angular bundle. High-frequency stimulation induced LTP in the dentate gyrus and probably also at other hippocampal termination sites. Retention in a later probe test was disrupted. When the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) was administered before the high-frequency stimulation, water maze retention was unimpaired. CPP administration blocked the induction of LTP. Thus, high-frequency stimulation of hippocampal afferents disrupts memory retention only when it induces a change in the spatial pattern of synaptic weights. The NMDA receptor dependency of this retrograde amnesia is consistent with the synaptic plasticity and memory hypothesis. (+info)
Theta rhythm of hippocampal CA1 neuron activity: gating by GABAergic synaptic depolarization.
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Information processing and memory consolidation during exploratory behavior require synchronized activity known as hippocampal theta (theta) rhythm. While it is well established that the theta activity depends on cholinergic inputs from the medial septum/vertical limb of the diagonal band nucleus (MS/DBv) and theta discharges of GABAergic interneurons, and can be induced with cholinergic receptor agonists, it is not clear how the increased excitation of pyramidal cells could occur with increased discharges of GABAergic interneurons during theta waves. Here, we show that the characteristic theta activity in adult rat hippocampal CA1 pyramidal cells is associated with GABAergic postsynaptic depolarization and a shift of the reversal potential from Cl(-) toward HCO(3)(-) (whose ionic gradient is regulated by carbonic anhydrase). The theta activity was abolished by GABA(A) receptor antagonists and carbonic anhydrase inhibitors, but largely unaffected by blocking glutamate receptors. Carbonic anhydrase inhibition also impaired spatial learning in a water maze without affecting other sensory/locomotor behaviors. Thus HCO(3)(-)-mediated signaling, as regulated by carbonic anhydrase, through reversed polarity of GABAergic postsynaptic responses is implicated in both theta and memory consolidation in rat spatial maze learning. We suggest that this mechanism may be important for the phase forward shift of the place cell discharges for each theta cycle during the animal's traversal of the place field for that cell. (+info)
Memory and executive function in sporadic and familial Parkinson's disease.
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Some studies have demonstrated that the motor symptomatology in sporadic and familial Parkinson's disease was identical. From a physiopathological point of view, and perhaps in the future from a therapeutic point of view, it seems important to determine whether sporadic and familial Parkinson's disease are also similar with regard to cognitive impairment. The aim of the present study was to assess cognitive functions in patients suffering from sporadic and familial Parkinson's disease. Executive functions and memory were investigated in particular. Two groups of 12 patients with Parkinson's disease (sporadic and familial) and 12 healthy controls performed a set of tasks known to evaluate different aspects of executive function and memory. One-way analysis of variance tested for significant group effects, and when justified, post hoc analysis was performed. Cognitive impairment was different in sporadic and familial forms of Parkinson's disease. Indeed, although executive function was impaired in both groups of patients, deficits in tests of explicit memory recall were only observed in patients with sporadic Parkinson's disease. Although the impairment observed in both groups of patients suggests a disruption of the striatoprefrontal circuits, this disruption seems to be quantitatively more important and more widespread in the sporadic patients than in the familial ones. In both patient groups, the deficits probably result from dopaminergic and nondopaminergic deprivation and a greater participation of nondopaminergic factors in patients with sporadic Parkinson's disease could be suggested. In this group, a xenobiotic could be responsible for an acquired metabolic defect involving more widespread structures of the striatoprefrontal circuits, leading to disruption of nondopaminergic loops. Cholinergic deprivation is considered in particular. (+info)