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PubMed1989

Mamillary bodies in Alzheimer's disease.

The number of senile (neuritic) plaques (SP) and neurofibrillary tangles (NFT) in mamillary bodies (MB) and in the dorsomedial nucleus of the thalamus (DMNT) were assessed in 25 cases of definite Alzheimer's disease. In 20 cases with AD without other CNS disease the MB and DMNT showed SP and/or NFT in 19 (95%). No correlation was found between the number of SP and NFT and the duration or age of onset of the disease. In patients with AD plus another CNS disease, there were fewer SP and NFT regardless of duration and age at onset of the disease. AD is a diffuse disorder with cortical and subcortical changes. The involvement of MB and DMNT suggests that subcortical structures are also implicated in the memory disorder of AD. The association of AD with other diseases that can themselves cause dementia requires further studies, especially regarding the pattern of topographic distribution of the degenerative changes.

Aged↗

PubMed1998

[Verbal short-term memory deficit in Alzheimer's disease: an examination with the free recall paradigm].

To examine the relationship between short-term memory deficit and severity of the dementia in Alzheimer's disease, free recall of word lists was investigated. Twenty-seven patients with diagnosis of probable Alzheimer's disease according to NINCDS ADRDA criteria, and twelve age-matched controls participated in the study. Patients were divided into two subgroups: fourteen mild and thirteen moderate dementia by Clinical Dementia Rating (CDR). To evaluate short-term and long-term memory components separately, two measures were used: recency effect in the serial-position free-recall curve, and intra-trial retention interval developed by Tulving and Colotla (1970). Mildly demented patients showed a long-term memory deficit with almost normal short-term memory, but moderate ones showed an overall reduction in both measures. These results suggest that memory disorder in Alzheimer's disease changes not only quantitatively but also qualitatively with the progress of dementia, and short-term memory is relatively preserved in the early stage of the disease.

Aged↗

PubMed1995

[Role of biological clock in human pathology].

Most of the vegetative, hormonal and behavioural functions of the human organism operate under the biological control of a circadian clock which responds to environmental and social stimuli, synchronizing the organism's physiology to daily and seasonal rhythms. The underlying anatomic structures are located in the suprachiasmatic nucleus and the pineal gland. Although the precise physiologic mechanisms involved are still under study, melatonin is known to play a major role. Normal function of the circadian clock is disrupted in jet-lag, night-shift work, and blindness as well as in rare cases of lesions to the pineal gland leading to a shift in biological rhythms including hormone secretion and control of body temperature, for example. Several signs of impaired function have been identified: various types of sleep disorders, memory and concentration impairment, dysphoria, asthenia, irritability. Seasonal recurrence of such signs and frequent depressive complications are also suggestive of a disorder in the circadian clock. Knowledge of specific clinical signs and biological parameters will undoubtedly lead to the discovery of other disease states dependant on the circadian clock and to the development of therapeutic strategies capable of regulating the organism's chronobiology.

Biological Clocks↗

PubMed2006

Emotional memory in depersonalization disorder: a functional MRI study.

This study examines emotional memory effects in primary depersonalization disorder (DPD). A core complaint of DPD sufferers is the dulling of emotional responses, and previous work has shown that, in response to aversive stimuli, DPD patients do not show activation of brain regions involved in normal emotional processing. We hypothesized that DPD sufferers would not show the normal emotional enhancement of memory, and that they would not show activation of brain regions concerned with emotional processing during encoding and recognition of emotional verbal material. Using fMRI, 10 DPD patients were compared with an age-matched healthy control group while performing a test of emotional verbal memory, comprising one encoding and two recognition memory tasks. DPD patients showed significantly enhanced recognition for overtly emotive words, but did not show enhancement of memory for neutral words encoded in an emotive context. In addition, patients did not show activation of emotional processing areas during encoding, and exhibited no substantial difference in their neural responses to emotional and neutral material in the encoding and emotional word recognition tasks. This study provides further evidence that patients with DPD do not process emotionally salient material in the same way as healthy controls, in accordance with their subjective descriptions of reduced or absent emotional responses.

Adult↗

PubMed1996

Do long tests yield a more accurate diagnosis of dementia than short tests? A comparison of 5 neuropsychological tests.

OBJECTIVE: To provide comparative evidence for a valid and practical measure of mental-status functioning that could be used in dementia clinics. DESIGN: Five mental-status neuropsychological tools for dementia screening were administered to patients in a memory disorder clinic. These included the Mini-Mental State Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation-Memory-Concentration Test, a short Mental Status Questionnaire, and a composite tool we labeled the Ottawa Mental Status Examination, which assessed orientation, memory, attention, language, and visual-constructive functioning. The tools were compared using various criteria, including the statistical factors of sensitivity and reliability; effects of gender, native language, and language of testing; the utility of these tests for the differential diagnosis of Alzheimer-type and vascular dementia; and sensitivity to cognitive decline in the entire sample and among patients with severe dementia. RESULTS: All of the tests were highly intercorrelated, suggesting that they are interchangeable. CONCLUSION: The comparisons along the various criteria indicate that if the objective is to have a general index of dementia of the Alzheimer type, short tests are at least as good and sometimes better than the longer tests.

Aging↗

PubMed2000

Deficits in spatial learning and nicotinic-acetylcholine receptors in older, spontaneously hypertensive rats.

Spontaneously hypertensive rats are often used as models of attention deficit hyperactivity disorder and to investigate the effects of hypertension on cognitive function. Along with the wide variety of cardiovascular anomalies, these animals as young adults also exhibit deficits in memory and attention and central nicotinic-acetylcholine receptor sites. These findings may have particular significance since nicotinic receptors appear to be involved in the regulation of cerebral circulation and mnemonic function. Furthermore, a lack of high affinity nicotinic receptors (in knockout mice) has also been shown to accelerate both the structural and cognitive degeneration associated with age, findings that may be especially relevant to age-related memory disorders such as Alzheimer's Disease where large deficits in nicotinic receptors are observed. Since spontaneously hypertensive rats appear to be both memory-impaired and deficient in nicotinic receptors at a young age (compared to the non-hypertensive phenotype, Wistar-Kyoto rats), we were interested to learn if these conditions were exacerbated in older animals with particular interest in specific nicotinic receptor subtypes in memory areas of the brain. Spatial learning was assessed in 15-month-old subjects of each phenotype (i.e. hypertensive and non-hypertensive) using a two-phase water maze paradigm, and nicotinic receptors were measured via autoradiography with [125I]-alpha-bungarotoxin and [3H]-epibatidine. In the water maze, both groups learned to locate a hidden platform as indicated by progressively shorter latencies across training days, however, Wistar-Kyoto rats were more efficient in both phases. While the number of both bungarotoxin and epibatidine binding sites was lower in the hypertensive rats across several brain regions, in the case of epibatidine binding, the magnitude of the difference and the number of areas affected was generally greater and included areas important for spatial learning (e.g. frontal and entorhinal cortex). In a direct comparison between 3-month-old and 15-month-old rats of each phenotype, epibatidine sites were markedly reduced by age (i.e. by greater than 50% in some cases) across multiple brain regions in both groups, although Wistar-Kyoto rats appeared to be more substantially affected by age. These data further support the use of the spontaneously hypertensive rat as model for studying learning-impairment and reduced central nicotinic receptors and also indicate that these characteristics persist and (in the case of high affinity nicotinic receptor cites) worsen with age.

Acetylcholine↗

PubMed1996

Diagnosis of dementia. Methods for interpretation of scores of 5 neuropsychological tests.

OBJECTIVE: To provide methods to interpret and compare different neurobehavioral screening tests for the diagnosis of dementia. DESIGN: Five mental-status neuropsychological tools for dementia screening were administered to patients in a memory disorder clinic. These included the Mini-Mental State Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation-memory-Concentration Test, a short Mental Status Questionnaire, and a composite tool we labeled the Ottawa Mental Status Examination, which assessed orientation, memory, attention, language, and visual-constructive functioning. RESULTS: To obtain z and percentile scores, norms are for the different tests, computed separately for patients with dementia of the Alzheimer type, vascular dementia, or no dementia. Another set of norms is reported in which a test score is translated directly into the posttest probability of dementia. Translation formulas are given to allow the estimation of the score on one test from the result on another test. CONCLUSION: The interpretation of tests used to diagnose dementia must be based on an understanding of the meaning of an individual score, which is based on the question asked and the population to which the patient is referenced.

Alzheimer Disease↗

PubMed1999

Transient amnesia triggered by acute marijuana intoxication.

We report an unusual case of sudden isolated transient amnesia triggered by acute marijuana use. The memory disorder, apart from the long duration, had the characteristics of a transient global amnesia-like episode. Acute marijuana intoxication can affect memory more globally and severely than previously reported.

Acute Disease↗

PubMed1997

No difference in cerebral glucose metabolism in patients with Alzheimer disease and differing apolipoprotein E genotypes.

BACKGROUND: Recent findings of a reduced cerebral metabolic rate of glucose (CMRGlu) in at-risk relatives of patients with Alzheimer disease (AD) who carry the apolipoprotein E (APOE) epsilon 4 allele suggest a causative role for the E4 isoform in cognitive changes that lead to AD. It is not known whether epsilon 4 allele-associated deficits exist in patients with clinical AD. OBJECTIVE: To determine whether distinct patterns of cerebral hypometabolism exist in patients who carry the epsilon 4 allele. PATIENTS AND METHODS: Information on the CMRGlu and APOE genotype was available for 46 patients at a memory disorders clinic: 31 patients were diagnosed as having probable AD, 3 demented patients did not meet criteria for AD, and 12 patients had mild memory complaints. Positron emission tomography with the use of 18F-fludeoxyglucose was used to calculate the CMRGlu in the frontal and temporoparietal regions of the cortex. Estimates were standardized to the sensorimotor area of the cortex. Linear regression models were constructed to relate the APOE genotype to the CMRGlu, adjusting for cognitive status (ie, the Mini-Mental State Examination score). RESULTS: Distinct patterns of the CMRGlu did not emerge for patients with different APOE genotypes. Bilateral deficits in the CMRGlu were found in the patients with AD. Left-right asymmetry was found in 8 of 12 patients with mild memory complaints: 7 of 8 had CMRGlu ratio less than 0.85 in the left side of the temporoparietal region of the cortex. CONCLUSIONS: The APOE epsilon 4 allele does not appear to be associated with specific deficits in brain metabolism in patients with AD despite evidence that the epsilon 4 allele is associated with preclinical alterations. This finding is consistent with previous epidemiologic results that have demonstrated a higher risk for AD in carriers of the epsilon 4 allele, but no change in the rate of progression of AD.

Adult↗

PubMed1991

[The diagnosis and therapy of depressive syndromes in old age].

Although depressions are the most frequent psychic disorders in the elderly diagnosis is often delayed and differential diagnosis complicated by other functional syndromes. Prevalent somatic symptoms such as somatic dysesthesias, pain, memory disorders and disorders of performance often mislead diagnostic search particularly if depressive alterations of mood are less prominent. Therefore history gains special importance beside physical examination. Three main groups are distinguished: --symptomatic (exogenous) depression --neurotic (reactive) depression --so called tardive depression Detection of nosologic connections is difficult but a prerequisite for a successful therapeutic approach. To this end particular attention should be given to connections between development of depression and history of life and coping with special events of life.

Adaptation, Psychological↗

PubMed1980

Transient global amnesia--a hippocampal phenomenon?

A case of transient global amnesia of clear vascular aetiology is described. Results of neuropsychological testing carried out during the attack clarify the nature of the memory disorder and suggest that the critical region of ischaemia is the medial temporal area around the hippocampus. Follow-up testing suggests that no lasting memory impairment resulted.

Adult↗

PubMed1985

[Post-traumatic deficit syndromes].

We discuss the evolution of psychological disorders following head injury. Even when the trauma seems mild at first, it may then give rise to cerebral lesions, particularly in the brain stem. Cerebral contusions in closed head injuries are responsible for consciousness disorders of varying duration, which are followed by mental confusion. At this point akinetic mutism or a Kluver and Bucy syndrome may appear. We consider memory disorders and other cognitive ones, the focus being on psychiatric disturbances of various kind.

Akinetic Mutism↗

PubMed2001

Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, 'ecstasy') and other substances.

A 26-year-old woman suffered disseminated intravascular coagulation (DIC) and a brief respiratory arrest following recreational use of 3,4-methylene-dioxymethamphetamine (MDMA; 'ecstasy'), together with amyl nitrate, lysergic acid (LSD), cannabis and alcohol. She was left with residual cognitive and physical deficits, particularly severe anterograde memory disorder, mental slowness, severe ataxia and dysarthria. Follow-up investigations have shown that these have persisted, although there has been some improvement in verbal recognition memory and in social functioning. Magnetic resonance imaging and quantified positron emission tomography investigations have revealed: (i) severe cerebellar atrophy and hypometabolism accounting for the ataxia and dysarthria; (ii) thalamic, retrosplenial and left medial temporal hypometabolism to which the anterograde amnesia can be attributed; and (iii) some degree of fronto-temporal-parietal hypometabolism, possibly accounting for the cognitive slowness. The putative relationship of these abnormalities to the direct and indirect effects of MDMA toxicity, hypoxia and ischaemia is considered.

Adult↗

PubMed2003

SR141716A, a cannabinoid CB1 receptor antagonist, improves memory in a delayed radial maze task.

An endogenous cannabinoid system may play an important role in controlling memory processes. SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride), a selective cannabinoid CB(1) receptor antagonist, was studied in an eight-arm radial maze task in which either deficits or improvements in memory could be detected. This task required well-trained rats to recall after either a relatively short (3 h) or long (7 h) delay period where they had received rewards during an information phase in order to obtain the remaining rewards during a retention phase. SR141716A was administered intraperitoneally immediately after the information phase in order to determine the drug's effects on memory consolidation. Although SR141716A had no effect on the number of errors committed after a short interval, SR141716A significantly reduced the number of errors that occurred after 7 h. These results suggest that a cannabinoid CB(1) receptor antagonist can improve consolidation processes and thus may be useful in treating memory disorders.

Animals↗

PubMed2003

Effects of subconvulsive electrical stimulation to the hippocampus on emotionality and spatial learning and memory in rats.

OBJECTIVE: To observe the effects of repeated subconvulsive electrical stimuli to the hippocampus on the emotional behavior and spatial learning and memory ability in rats. METHODS: One hundred and eight male Wistar rats were randomized into 3 groups. Animals in group SE (n = 42) were given subconvulsive electrical stimulation to the hippocampus through a constant pulsating current of 100 mu A with an intratrain frequency of 25 Hz, pulse duration of 1 millisecond, train duration of 10 seconds and interstimulus interval of 7 minutes, 8 times a day, for 5 days. In the electrode control group or CE group (n = 33), animals were implanted with an electrode in the hippocampus, but were not stimulated. Group NC (n = 33) animals received no electrode or any stimulation. The emotional behavior of experimental rats was examined by activity in an unfamiliar open field and resistance to capture from the open field, while the spatial learning and memory ability was measured during training in a Morris water maze. RESULTS: The stimulated rats tested 1 month after the last round of stimulation displayed substantial decreases in open field activity (scale: 10.4 +/- 2.3, P < 0.05) and increases in resistance to capture (scale: 2.85 +/- 0.56, P < 0.01). The amount of time for rats in group SE to find the platform (latency) as a measurement for spatial bias was prolonged (29 +/- 7) seconds after 15 trials in the water maze, P < 0.05). The experimental rats swam aimlessly in all four pool quadrants during the probe trial in the Morris water maze. CONCLUSIONS: Following repeated subconvulsive electrical stimuli to the hippocampus, rats displayed long-lasting significant abnormalities in emotional behavior, increased anxiety and defensiveness, enhanced ease to and delayed habituation to startlement, transitory spatial learning and memory disorder, which parallels many of the symptoms in posttraumatic stress disorder patients.

Animals↗

PubMed1980

Sensory-specific and fractional disorders of recent memory in man. I. Isolated loss of visual recent memory.

Two patients who lost, in isolation, visual recent memory following bilateral posterior cerebral artery infarctions are described. Tactile, verbal, and nonverbal auditory recent memory functions were preserved in both patients. Based on computerized tomography scans and behavioral and anatomical data in monkey, isolated loss of visual recent memory in man is best understood as a bilateral disconnection syndrome between the striate cortex and the structures in the medial temporal lobe that are involved with recent memory. The possible existence of two other sensory-specific disorders of recent memory, tactile and auditory, is postulated, and the clinical relationship of prosopagnosia, achromatopsia, and spatial disorientation to visual recent memory loss is discussed.

Adult↗

PubMed1994

Muscarinic receptors and novel strategies for the treatment of age-related brain disorders.

The muscarinic class of acetylcholine receptors is widely distributed throughout the body and mediates numerous vital functions in both the brain and autonomic nervous system. Within the brain, muscarinic receptors play an important role in learning, memory and the control of posture. There is a decrease in the synthesizing enzyme for acetylcholine in Alzheimer's disease, and damage to the ascending cholinergic system is thought to be an important determinant of the loss of memory and other functional deficits of this disease. Five subtypes of the muscarinic receptor (m1-m5) have been identified, and these receptors have a differential distribution throughout the body. The differential distribution of subtypes of the muscarinic receptor in the body suggests that centrally acting m1 and m4 muscarinic agonists might be efficacious in the treatment of age-related memory disorders, without causing peripheral side effects. In addition to the primary ligand binding site, muscarinic receptors also possess a secondary allosteric site that appears to be the target for some novel cardioselective muscarinic antagonists including the neuromuscular blocking agent gallamine. The existence of a secondary allosteric site on the muscarinic receptor suggests that it might be possible to develop novel allosteric muscarinic agonists that potentiate the effects of endogenous acetylcholine much in the same way that benzodiazepines potentiate GABA. Although no such allosteric muscarinic agonists have been identified to date, they could be very efficacious in the treatment of Alzheimer's disease.

Aging↗

PubMed2004

Clinical applications of cognitive event-related potentials in Alzheimer's disease.

This article has reviewed several abnormalities in the cognitive ERPs of AD patients. These abnormalities are prominent from latencies of approximately 200 msec and later. In contrast, sensory-dependent evoked potentials, such as N100, are generally normal in AD. This finding is as one familiar with the neuropathology of AD would predict. Predilection sites in early AD include the medial temporal lobe, other limbic areas, and multimodal association cortices with sparing of primary sensory areas. Unimodal association cortex is involved in AD, but not as heavily as multimodal cortex. Particular advantages of studying a given ERP paradigm or component depend largely on the specific application or hypothesis being tested. A P300 paradigm can be useful in detecting a disorder of attention or in quantifying the effects of drugs that improve attention, such as the cholinesterase inhibitors. For the early diagnosis of AD or other memory disorders, a word-repetition paradigm with an explicit recognition task or one that fosters associative learning would be recommended. This article has discussed potential use of N400 in tracking disease progression. ERPs provide a flexible and powerful technique, with superb temporal resolution, which can be used as a probe into subtle "subclinical" abnormalities of cognitive processes. Despite being applied to AD for about 25 years since the early P300 studies, the full potential of ERPs in helping diagnose and treat AD patients has yet to be realized. In this era of rapidly evolving brain-imaging techniques, electrophysiologic data are important in advancing understanding of cognition. Brain-mapping techniques that can inform where and when key cognitive processes occur are finally emerging. A final example of potential clinical application of cognitive ERPs is in the development of rational combinational treatment of cognitive enhancing drugs. Along these lines, P300 investigations in epilepsy proved helpful in ranking the cognitive side effects of anticonvulsant drugs. Drug studies that use 2 x 2 combinational designs, which compare the effects of drug A, drug B, with A + B, are currently prohibitively expensive for full-scale clinical trials in AD. It is likely that precise ERP measures could hasten drug development in several ways. Smaller samples could be used, at lower cost, to test the cognitive effects of each specific drug combination. Optimal doses of combinational therapy perhaps could be identified by repeated within-subject ERP measures. Longitudinal changes in the ERP hold promise as a marker of individual responsivity to a particular agent, which could have diagnostic utility (eg, testing response to cholinergic or dopaminergic therapy). This horizon and many others remain wide open for well-planned explorations.

Aging↗