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Selective sparing of face learning in a global amnesic patient.

OBJECTIVE: To test the hypothesis that visual memory for faces can be dissociated from visual memory for topographical material. METHOD: A patient who developed a global amnesic syndrome after acute carbon monoxide poisoning is described. A neuroradiological examination documented severe bilateral atrophy of the hippocampi. RESULTS: Despite a severe anterograde memory disorder involving verbal information, abstract figures, concrete objects, topographical scenes, and spatial information, the patient was still able to learn previously unknown human faces at a normal (and, in some cases, at a higher) rate. CONCLUSIONS: Together with previous neuropsychological evidence documenting selective sparing of topographical learning in otherwise amnesic patients, this case is indicative of the fact that the neural circuits involved in face recognition are distinct from those involved in the recognition of other visuoperceptual material (for example, topographical scenes).

Acute Disease↗

Psychological dysfunction accompanying subcortical dementias.

Subcortical dementia occurs both in disorders affecting the basal ganglia (for example, Parkinson's disease, Huntington's disease, and progressive supranuclear palsy) and in a variety of subcortical vascular, infectious, inflammatory, neoplastic, and traumatic conditions. The principal features of subcortical dementia include bradyphrenia, impairment of executive function, recall abnormalities, visuospatial disturbances, depression, and apathy. The syndrome contrasts with dementia of the Alzheimer type in which cortical involvement produces aphasia, combined recall and recognition deficits, and indifference. Electrophysiologic, biochemical, and metabolic studies support a distinction between subcortical and cortical dementias.

Affective Disorders, Psychotic↗

5-ht6 receptors as emerging targets for drug discovery.

5-ht6 receptors are the latest serotonin receptors to be identified by molecular cloning. Their high affinity for a wide range of drugs used in psychiatry, coupled with their intriguing distribution in the brain, has stimulated significant interest. Antisense oligonucleotides, antipeptide antibodies, selective radioligands, knockout mice, and selective antagonists of the 5-ht6 receptor have recently become available. Surprisingly, 5-ht6 receptors appear to regulate cholinergic neurotransmission in the brain, rather than the expected interaction as modulators of dopaminergic transmission. This interaction predicts a possible role for 5-ht6 receptor antagonists in the treatment of learning and memory disorders. Furthermore, polymorphisms in the sequence of the 5-ht6 receptor gene may provide a genetic tool to further our understanding of the differential responses of patients to antipsychotic medications.

Animals↗

Fate of patients with questionable (very mild) Alzheimer's disease: longitudinal profiles of individual subjects' decline.

Currently used criteria for the diagnosis of probable Alzheimer's disease requires the presence of cognitive deficit in addition to loss of episodic memory. The recent developments in drug treatments for Alzheimer's disease have highlighted the importance of early diagnosis and the need to characterise the cognitive profile of the earliest stages of the disease. We set out to examine the pattern of decline in terms of individual cognitive domains in non-demented subjects with clinically isolated progressive amnesia which we have termed questionable Alzheimer's disease. Twelve subjects who fulfill criteria for a clinical diagnosis of possible Alzheimer's disease by NINCDS-ADRDA criteria were compared to 20 age-matched controls in a longitudinal study. All subjects had MMSE scores of 24 or greater at entry to study. Individual profiles were measured by impairment in the cognitive domains of episodic memory, attention, semantic memory, visuospatial function and auditory verbal short-term (working) memory. Even after subjects were given this intensive neuropsychological battery, 8 of 12 subjects had episodic memory deficits only. Within 12 months just 3 patients were only amnesic and the other patients with pure amnesia at year 1 developed either semantic or attentional deficits. Impairment in both these cognitive domains preceded impairment in visuospatial function and auditory-verbal short-term memory. Our findings are consistent with the pattern of cognitive impairment in Alzheimer's disease increasing in accordance with neuropathological correlates of cognitive function with amnesia linked to the initial medial temporal pathology before the pattern of spread affects critical neural substrates for attention and semantic memory. Tests of selective attention and semantic memory appear to be the most sensitive markers of decline beyond the amnestic phase of early Alzheimer's disease.

Aged↗

The relationship between apolipoprotein E4 and lipid metabolism is impaired in Alzheimer's disease.

BACKGROUND: Human apolipoprotein (Apo) E4 (ApoE4) is an important determinant of lipid metabolism and cell-to-cell cholesterol transport. It is also a major genetic risk factor for both vascular disease and familial and sporadic late-onset Alzheimer's disease (AD). Since vascular pathology could dramatically reduce neuronal reserve capacity, a biological chain of events between ApoE4, hypercholesterolemia and AD has been postulated. The aim of the present study is to explore the relationship between lipid metabolism and ApoE isoforms in a large series of elderly subjects in relation to the presence or absence of AD. METHODS: Of 332 referrals to a neurology clinic specializing in memory disorders, 146 were given a diagnosis of AD (age, mean +/- SD 76 +/- 13.1 years, 64.4% women) according to DSM-IIIR criteria. One hundred and seventy-six subjects were included as controls (age 80 +/- 5.6 years, 58% women). The ApoE phenotype was determined by the isoelectrofocalization method, cholesterol, triglycerides, phospholipids, ApoA and ApoB were determined by routine chemistry. FINDINGS: A significant association was observed between the E4 allele and AD (chi2 = 13, p < 0.001) only below age 80. In the control group, cholesterol levels were found to be significantly higher in men but not in women with an E4 allele (6.35 +/- 1.3 mmol/l) as opposed to those without (5.8 +/- 1.2 mmol/l). ApoB levels were also found to be higher in the presence of ApoE4, with no gender effect. Within the AD group no significant relationship was found between ApoE4 and cholesterol levels (mean 6.05 +/- 0.9 mmol/l in E4-AD subjects versus 5.8 +/- 1.21 mmol/l in non-E4-AD subjects). Similar observations were made in relation to triglycerides and phospholipids. INTERPRETATION: Our results demonstrate the disappearance of the ApoE4-raising effect on serum cholesterol, triglyceride and phospholipid levels in AD suggesting a more complex relationship between AD and lipid metabolism than has previously been supposed. This lipid abnormality may further contribute to the progression of AD.

Aged↗

Impaired motor learning in children with hydrocephalus.

Hydrocephalic (n = 19) and normal (n = 20) children in two age groups (averaged at 10 and 14 years old) were asked to learn 5 predetermined timing rhythm interval tasks (including timing duration and relative timing pattern) by pressing keys on a computer keyboard. In the acquisition phase, visual and auditory goal timing intervals, as well as visualized feedback were presented to all participants before and after their key presses, respectively. A retention test without the auditory information and visualized feedback was administered 1 day later. By using the computerized timing test, we demonstrated in this study that the hydrocephalic group had significantly (ANOVA analysis) increased relative timing errors; this function depends on the formation of an internal model or a motor program related to long-term memory disorders. These findings could lead to the formulation of training procedures with simplified movements that may help hydrocephalic children improve their motor skill learning.

Adolescent↗

Poor frequency discrimination probes dyslexics with particularly impaired working memory.

Substantial difficulties in performing simple auditory discriminations were previously found in some individuals with a specific reading disability but not in others. This high variability in psychoacoustic performance raises the question of whether this difficulty is related to the reading deficit. Addressing this question, we compared adult dyslexics with and without difficulty in simple auditory discriminations, using 2-tone frequency discrimination as our probe. The distribution of their frequency discrimination scores was bimodal. On this basis, we divided our participants into subgroups having either poor or adequate psychoacoustic performance. Only dyslexics with poor psychoacoustic scores had significantly impaired verbal working memory compared to their matched controls. Furthermore, and only in this subgroup, working memory scores were correlated with both cognitive abilities and reading-related tasks. Consistent with the hypothesis that in this subgroup poor working memory impedes performance in a broad range of academically related tasks, we found that the majority of dyslexics in this subgroup had more extensive academic difficulties and consequently needed special support in schools. We propose that dyslexics with poor psychoacoustic abilities form a distinct subtype of dyslexia in which the core deficit is not specific to phonological components. For these individuals, poor verbal working memory may be the main impediment to success in academic environments.

Adolescent↗

Evaluating spousal abuse as a potential risk factor for Alzheimer's disease: rationale, needs and challenges.

BACKGROUND: Repetitive head trauma is an identified risk factor for Alzheimer's disease (AD). The violence in wife assault is repetitive and targets the head. This association provides a rationale for studying the relationship between spousal abuse and AD. DESIGN: To preliminarily evaluate the possibility of an increased susceptibility for AD in women subjected to spousal abuse and to identify challenges associated with such a study, we performed a pilot case-control study involving women with AD and compared the incidence of spousal abuse against two control groups. Forty consecutive women with AD referred to a Memory Disorders Clinic were enrolled. Individuals were evaluated at three visits (0, 3, 9 months) and were followed for an additional 12 months to ensure that no other diagnosis emerged. Two control groups were likewise assessed. RESULTS: 17.5% (7/40) of the women (average age 71 years) with AD reported spousal abuse with head trauma. In control group 1, 5.0% (2/40) and in control group 2, 7.5% (3/40) of the women reported spousal abuse with head trauma. CONCLUSIONS: The development of AD may be a potential long-term consequence of wife assault. Our study suggests spousal abuse as a possible risk factor for AD, and supports the need for larger studies. However, there are practical challenges associated with the successful execution of such a study.

Aged↗

Obesity, abdominal obesity and Alzheimer disease.

BACKGROUND/AIMS: Obesity has a strong association with vascular and metabolic diseases, which have been linked with Alzheimer disease (AD). While recent studies have reported an association between mid-life obesity and dementia, the role of later-life obesity is less clear. This study investigated the relation between AD, obesity and abdominal obesity at later-life in a case-control study. METHODS: Participants were 50 consecutive patients with probable AD from memory disorders clinics in Launceston, Australia, and Bristol, England, and 75 cognitively normal controls. Height and weight [from which body mass index (BMI) was calculated] and hip and waist circumferences (from which waist-hip ratio was calculated) were measured. Participants were classified according to their BMI as: underweight (BMI <20.0 kg/m2); normal weight (BMI 20.0-24.9 kg/m2); overweight (BMI 25-29.9 kg/m2), or obese (BMI > or = 30 kg/m2). They were classified as abdominally obese if their waist-hip ratio was >0.9 (men) or >0.8 (women). RESULTS: AD was associated with obesity [OR 9.5, 95% CI 2.4-37.3, p = 0.001], underweight (OR 5.4, CI 0.9-33.7, p = 0.07) and abdominal obesity (OR 2.5, CI 1.1-5.7, p = 0.027) using logistic regression analyses adjusted for age, sex and location. The inclusion of metabolic risk factors in the model increased the ORs for obesity (OR 12.6, CI 2.8-56.5, p = 0.001) and underweight (OR 7.9, CI 1.0-66.3, p = 0.056). CONCLUSION: AD may be associated with obesity, underweight and abdominal obesity at later life. Larger prospective studies are required to investigate this further.

Abdominal Fat↗

Chronic obstructive pulmonary disease and associated patterns of memory decline.

The relationship between chronic obstructive pulmonary disease (COPD) and cognitive functioning was analyzed in a study with 50 aging patients. A complex pattern of interactions was identified between emotional and cognitive functioning and chronic respiratory disease when the effects of age, sex, type and severity of disease were controlled. These patients did not show any global and diffuse cognitive impairment. Only a portion of COPD patients (about 30%) evidenced memory impairment which was confined to immediate memory. Memory impairment found in these patients did not appear to be associated with those changes present in the aging process but was mainly related to those specific clinical and instrumental parameters which are considered valid indicators of respiratory efficiency. Two types of cognitive and emotional problems were identified. A progressive stage-dependent set of characteristics was associated with the course of the disease and a fluctuating, probably reversible state-dependent set of characteristics was associated with the temporary condition of the patients during the period of examination. Patients who had received more recent medical treatment or who were under protection of vaccination for influenza showed a better cognitive and emotional efficiency.

Aged↗

Effect of sabeluzole (R 58,735) on memory functions in patients with epilepsy.

Sabeluzole, a new benzothiazol derivative, has shown positive effects on memory function in animals and in normal volunteers. The present study reports the results of sabeluzole, in memory-impaired patients with localization-related (partial) epilepsy. A randomized, double-blind placebo-controlled parallel-group design was used. A total of 38 patients entered a prospective baseline. Five patients dropped out from the study, thus 33 patients were randomly assigned to either a 12-weeks treatment with sabeluzole (n = 14) or placebo (n = 19). The treatment phase was preceded by a titration phase of 4 weeks to obtain serum levels of sabeluzole between 50 and 130 ng/ml. In order to maintain blindness, a sham titration was carried out in the placebo group. The number of 'responders', i.e. patients with a > 1 SD improvement on at least three of the memory tests was 9 out of 14 (64.3%) in the sabeluzole group and 7 out of 19 (36.8%) in the placebo group. This suggests a clinically relevant effect of sabeluzole. The analysis of the memory tests showed a statistically significant improvement with sabeluzole on the verbal long-term memory test. This could represent a specific drug effect and is in line with previous results of normal volunteer studies that also found improvement mainly restricted to the area of verbal long-term memory.

Adult↗

Transient loss of recent memory following deep midline cerebral operations.

We have drawn attention to a post-operative complication of deep midline cerebral operations where operative manipulation occurs to structures associated with memory mechanisms. In the cases presented, the deficit was not permanent probably because the lesions were unilateral, or in conduction pathways.

Adolescent↗

Emotional arousal can impair feature binding in working memory.

To investigate whether emotional arousal affects memorial feature binding, we had participants complete a short-term source-monitoring task-remembering the locations of four different pictures over a brief delay. On each trial, the four pictures were all either high arousal, medium arousal, or low arousal. Memory for picture-location conjunctions decreased as arousal increased. In addition, source memory for the location of negative pictures was worse among participants with higher depression scores. Two subsequent functional magnetic resonance imaging experiments showed that relative to low-arousal trials, high- and medium-arousal trials resulted in greater activity in areas associated with visual processing (fusiform gyrus, middle temporal gyrus/middle occipital gyrus, lingual gyrus) and less activity in superior precentral gyrus and the precentral-superior temporal intersect. These findings suggest that arousal (and perhaps negative valence for depressed people) recruits attention to items thereby disrupting working memory processes that help bind features together.

Adolescent↗