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PubMed1999

[Organization of memory centers and prospects].

The concept of memory centers is based on a multidisciplinary approach to memory disorders and dementia, especially Alzheimer's disease, a public health challenge. The first memory centers were established in the 80s in the US and the British Isles. The aims of these centers are to make a diagnosis (and to reassure the 'worried well'), to detect dementia, to provide a service for their management, to educate care takers, to evaluate new therapies, and to contribute to clinical and basic research. Follow-up is crucial. The first memory centers all experienced long delay to diagnosis of dementia and found that Alzheimer's disease was the first cause of consultation. These observations led to the creation of such centers in many countries. A survey of 20 French memory centers defined the "ideal memory center": an identified structure with a clinic and a day-care unit for diagnosis and follow-up, with neurological, psychological, psychiatric, and geriatric skills. It must be part of a medical and social network for the management of dementia and participate in a network of memory centers at the regional and national level. Relationships between dementia and somatic diseases, frequent in demented patients, are still poorly known. Dementia interferes with the clinical expression, the management, and the prognosis of somatic diseases, some of which, such as cardiovascular conditions, are possibly linked with dementia. Conversely, somatic diseases may rapidly worsen the cognitive state and induce delirium, leading to hospitalization. Medical wards are not all appropriate. Memory centers must also be involved in these care, educational and research issues.

Academic Medical Centers↗

PubMed1977

A study of confabulation.

Confabulation consequent to organic amnesia is a well-described clinical finding. A number of plausible theories of confabulation have been proposed, but the various claims and counterclaims have not been systematically tested. A standardized test battery that included four different kinds of questions plus measures of suggestibility and the tendency to utilize external cues was administered to ten amnesic patients who demonstrated varying degrees of confabulation. One additional patient, whose clinical condition changed dramatically during his hospital course, received the battery on a number of occasions. Differences among patients were found in overall performance, degree of confabulation, and ability to use cues. Hypothesized relationships between confabulation and suggestibility, degree of memory disorder, and degree of disorientation were not confirmed. However, confabulation proved to be strongly related to the inability to withhold answers, to monitor one's own responses and to provide verbal self-corrections. These results suggest a tentative model of the process of confabulation as well as a number of useful clinical signs indicationg recovery from amnesia.

Adult↗

PubMed2004

Nicotine improves delayed recognition in schizophrenic patients.

RATIONALE: Nicotine has been shown to enhance some aspects of memory, attention and cognition in normal subjects and in some patient populations such as Alzheimer's and Parkinson's disease groups. OBJECTIVES: Memory disorders are consistently observed in schizophrenic patients, so it is of interest to determine whether nicotine might improve memory performance in these patients. METHODS: Delayed recognition was assessed using yes/no recognition of visuospatial designs. Working memory was assessed in a delayed match-to-sample paradigm using unfamiliar faces. Nicotine (1.0 mg delivered via nasal spray) was administered to schizophrenic patients and normal volunteers prior to testing in the nicotine condition. Results were compared to a baseline condition in which no nicotine was given. RESULTS: On both tasks, normal volunteers performed better overall than schizophrenic patients. Significant improvement following nicotine administration was obtained only on the delayed recognition task and only for the subset of schizophrenic patients who were smokers. This improvement reflected a reduction in false alarm rates in the nicotine condition; hit rates were unaffected by nicotine. CONCLUSIONS: These results suggest that nicotine enhances delayed recognition memory in schizophrenic patients who smoke, but that similar performance enhancement is not observed for working memory.

Adult↗

PubMed1999

Mnestic block syndrome.

The case of a patient with largely preserved intelligence, but severe and persistent memory impairments is reported. FA, a 46-year-old patient with the diagnosis of prolonged depression was investigated repeatedly over a two year period with neuroradiological, neuropsychological, neuromonitoring and other methods. While no brain damage was detectable in FA, he manifested continued and severe anterograde and retrograde memory disorders together with an inhibition in his thinking processes. Otherwise, his intellectual capabilities were in the normal range, that is he was not pseudo-demented. Various approaches with drug treatment and psychotherapy failed to improve his condition. The condition is interpreted as 'mnestic block syndrome' and is considered to be related to an altered brain metabolism which may include changes in various transmitter and hormonal systems (GABA-agonists, glucocorticoids, acetylcholine). Whether depression contributes to this syndrome is uncertain from FA's cognitive performance, but may be a possibility.

Amnesia, Retrograde↗

PubMed1994

Disorders of semantic memory.

It is now established that selective disorders of semantic memory may arise after focal cerebral lesions. Debate and dissension remain on three principal issues: category specificity, the status of modality-dependent knowledge, and the stability and sufficiency of stored information. Theories of category specificity have focused on the frequently reported dissociation between living things and man-made objects. However, other dimensions need theoretical integration. Impairments can be both finer-grain and broader in range. A second variable of importance is stimulus modality. Reciprocal interactive dissociations between vision and language and between animals and objects will be described. These indicate that the derivation of semantic information is constrained by input modality: we appear to have evolved separable databases for the visual and the verbal world. Thirdly, an orthogonal distinction has been drawn between degradation disorders, where representations are insufficient for comprehension, and access deficits, in which representations have become unstable. These issues may have their parallel in the acquisition of knowledge by the developing child.

Adolescent↗

PubMedDate not supplied

[Which memory clinic and for whom?].

The burgeoning of interest in Alzheimer's disease since the early 1980s has resulted in the development of memory clinics to improve the diagnosis and management of patients with the disease. Some memory clinics, however, have a broader interest in memory disorders, especially in those associated with normal ageing. Some questions should be considered with regard to the activity of memory clinics: (1) should the patients be systematically subjected to a multidisciplinary team and standardized examinations or to a single specialist in charge of adjusting examinations and management to particular situations? (2) Who should be responsible for the financial cost of memory clinics: the patients, the National Health Service or research grants? Evaluation procedures should be set up as soon as possible to answer these questions.

Alzheimer Disease↗

PubMed2005

[A guide to diagnosis of Alzheimer's disease].

Despite the evolution of an increase of medical formation, only 50% of patients with Alzheimer's disease (AD) are diagnosed in France. It is pity, given the fact that the diagnosis of AD is relatively easy and can often be made without hospitalisation. The first stage of the medical inquiry is based on the clinical observation. It is established that the progression of the symptoms follows the progression of the brain lesions. A deficit in episodic memory is the earliest and most predominant cognitive change of AD. This is consistent with the precocious involvement of mesial temporal structures. This pattern, so-called "memory disorders of the hippocampal type," is highly suggestive of AD and markedly differs from that of other dementing illnesses. As the disease progresses and involves neocortical associative areas, patients demonstrate impairments in instrumental functions such as language, praxia, gnosia, and visuoconstructive functions. The second stage of the diagnosis is based on neuroimagery. MRI shows a bilateral atrophy of hippocampal formations even in the early stages of the disease. Standard biological parameters are normal. According to the context of occurrences of the disease or to the existence of atypical clinical or radiological changes, additional investigations can be proposed.

Aged↗

PubMed2006

Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment.

CONTEXT: The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established. OBJECTIVES: To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion. DESIGN: Patients were followed up semiannually and controls annually. Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures. SETTING: Memory disorders clinic. PARTICIPANTS: One hundred forty-eight patients reporting memory problems and 63 group-matched controls. MAIN OUTCOME MEASURE: A consensus diagnosis of probable AD. RESULTS: At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 +/- 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%. CONCLUSIONS: Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.

Aged↗

PubMed1990

The effects of THA on medial septal lesion-induced memory defects.

Electrolytic lesioning of the medial septum (MS) was used to assess the effectiveness of tacrine (THA) in reversing lesion-induced spatial memory deficits in a water-maze. Lesioned animals were injected with either 3 mg/kg or 5 mg/kg of THA intraperitoneally 15 min prior to daily behavioral training. One group of the lesioned and sham-operated animals received saline. All animals underwent two training trials each day for a period of ten days, after which a spatial probe trial was performed and assessed. The accurate placement of MS lesions resulted in lowered acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity within the hippocampus of lesioned rats. Lesioning of the MS also impaired the learning performance in locating the escape platform during training and decreased the spatial bias during the probe trial. A lower dose of THA (3 mg/kg) significantly reversed the path length increase and spatial bias decrease induced by MS lesioning, but had no effect on escape latency. However, comparison between the saline- and THA- (5 mg/kg) injected MS-lesioned rats showed no significant differences in either escape latency or spatial bias. The present results support the use of cholinesterase inhibitors in further treatment trials of geriatric memory disorders.

Aminoacridines↗

PubMed1996

Aged garlic extract prolongs longevity and improves spatial memory deficit in senescence-accelerated mouse.

The effects of aged garlic extract (AGE), chronically administered in the diet, on longevity and spatial learning performances were studied using the senescence-accelerated mouse (SAM). A solid diet containing 2% AGE was given to senescence-accelerated-prone mouse 8 (SAMP8) and senescence-accelerated-resistant mouse 1 (SAMR1) from 2 months of age. The survival ratio of SAMP8, a substrain of senescence-accelerated-prone mouse, was significantly lower than that of SAMR1, a substrain of senescence-resistant mouse. In the SAMP8, administration of AGE perfectly prevented the decrease in survival ratio. Moreover, AGE markedly improved the learning deficits of SAMP8 in the Morris water maze test. These results suggest the possibility that AGE prevents physiological aging and age-related memory disorders in human.

Aging↗

PubMed1998

[Memory and dementia].

Memory impairment in ageing is clearly different from Alzheimer's disease. Many papers dealed with the modifications of the different cognitive sections of memory at different stages of Alzheimer's progression: the early involvement of working and episodic memories, those later of semantic and retrograde memories and the lasting saving of implicit memory must be know by clinicians to better understand the target of symptomatic therapy and to differentiate Alzheimer from others degenerative dementias. Above all, these progress authorize an early diagnostic of "possible Alzheimer" at a pre-dementia stage facing to isolated memory complaint. The amnesic profile of others dementias is different and the qualitative approach of testing become essential for the categorization of dementias at early stages with an isolated progressive memory disorder.

Alzheimer Disease↗

PubMed1989

A new scale for the assessment of functional status in Alzheimer's disease and related disorders.

Assessment of the functional competencies of patients with dementia is typically conducted in an indirect manner. Psychological tests of cognition or descriptions by relatives or other caregivers are often used to make judgments as to the patient's ability to adapt to the demands of the environment. However, these methods have built-in biases. The need for direct assessment of functional status was addressed by developing a standardized operational procedure to examine areas of functional competence which may become impaired in Alzheimer's disease and other related memory disorders. The resulting instrument has high interrater and test-retest reliabilities. Convergent validity is evidenced by significant correlations between the scale and established measures of functional status. Patients with Alzheimer's disease exhibited deficits in functional capacities relative to age-equivalent normal controls and to elderly patients with a primary major depression.

Activities of Daily Living↗

PubMed1999

Estrogen replacement therapy and cognitive decline in memory-impaired post-menopausal women.

BACKGROUND: Estrogen replacement therapy (ERT) may delay dementia-related cognitive decline in post-menopausal women, but few studies have longitudinally examined this relationship and none has controlled for baseline functioning or concurrent medication. METHODS: We report the results of a 1-year retrospective longitudinal study examining cognitive functioning in female estrogen and nonestrogen users (n = 3128) who presented to the state of California memory disorder clinics in a naturalistic multisite study of senile dementia, Alzheimer's type (SDAT), and other cognitive impairments. RESULTS: At baseline, estrogen users had significantly lower rates of SDAT diagnoses (possible and probable) than nonestrogen users, and significantly higher rates of the lesser diagnoses of "cognitive impairment" and "no dementia." ERT was significantly associated with higher cognitive functioning at baseline and at 1 year follow-up (n = 358). Nonestrogen users deteriorated significantly from baseline to follow-up; estrogen users did not. Results were similar in groups matched on baseline Blessed-Roth Dementia Rating Scale (BRDRS) ratings (n = 32) and in a variety of subpopulations. CONCLUSIONS: These findings are consistent with estrogen acting as a protective factor against cognitive deterioration in post-menopausal women with SDAT and other cognitive impairments, and may suggest an increased effect in earlier stages of cognitive impairment.

Aged↗

PubMed2002

Dynamic imaging in mild traumatic brain injury: support for the theory of medial temporal vulnerability.

OBJECTIVE: To determine whether patients with mild traumatic brain injury (TBI) and persistent postconcussive symptoms have evidence of temporal lobe injury on dynamic imaging. DESIGN: Case series. SETTING: An academic medical center. PARTICIPANTS: Twenty patients with a clinical diagnosis of mild TBI and persistent postconcussive symptoms were referred for neuropsychologic evaluation and dynamic imaging. Fifteen (75%) had normal magnetic resonance imaging (MRI) and/or computed tomography (CT) scans at the time of injury. INTERVENTIONS: Neuropsychologic testing, positron-emission tomography (PET), and single-photon emission-computed tomography (SPECT). MAIN OUTCOME MEASURES: Temporal lobe findings on static imaging (MRI, CT) and dynamic imaging (PET, SPECT); neuropsychologic test findings on measures of verbal and visual memory. RESULTS: Testing documented neurobehavioral deficits in 19 patients (95%). Dynamic imaging documented abnormal findings in 18 patients (90%). Fifteen patients (75%) had temporal lobe abnormalities on PET and SPECT (primarily in medial temporal regions); abnormal findings were bilateral in 10 patients (50%) and unilateral in 5 (25%). Six patients (30%) had frontal abnormalities, and 8 (40%) had nonfrontotemporal abnormalities. Correlations between neuropsychologic testing and dynamic imaging could be established but not consistently across the whole group. CONCLUSIONS: Patients with mild TBI and persistent postconcussive symptoms have a high incidence of temporal lobe injury (presumably involving the hippocampus and related structures), which may explain the frequent finding of memory disorders in this population. The abnormal temporal lobe findings on PET and SPECT in humans may be analogous to the neuropathologic evidence of medial temporal injury provided by animal studies after mild TBI.

Adult↗

PubMed2003

Developmental amnesia: effect of age at injury.

Hypoxic-ischemic events sustained within the first year of life can result in developmental amnesia, a disorder characterized by markedly impaired episodic memory and relatively preserved semantic memory, in association with medial temporal pathology that appears to be restricted to the hippocampus. Here we compared children who had hypoxic-ischemic events before 1 year of age (early group, n = 6) with others who showed memory problems after suffering hypoxic-ischemic events between the ages of 6 and 14 years (late group, n = 5). Morphometric analyses of the whole brain revealed that, compared with age-matched controls, both groups had bilateral abnormalities in the hippocampus, putamen, and posterior thalamus, as well as in the right retrosplenial cortex. The two groups also showed similar reductions (approximately 40%) in hippocampal volumes. Neuropsychologically, the only significant differences between the two were on a few tests of immediate memory, where the early group surpassed the late group. The latter measures provided the only clear indication that very early injury can lead to greater functional sparing than injury acquired later in childhood, due perhaps to the greater plasticity of the infant brain. On measures of long-term memory, by contrast, the two groups had highly similar profiles, both showing roughly equivalent preservation of semantic memory combined with marked impairment in episodic memory. It thus appears that, if this selective memory disorder is a special syndrome related to the early occurrence of hypoxia-induced damage, then the effective age at injury for this syndrome extends from birth to puberty.

Adolescent↗

PubMedDate not supplied

[The clinico-neuropsychological aspects of arteriovenous malformations of the hippocampus].

A comprehensive examination was made in 39 patients with arteriovenous malformations (AVM) of hippocampus. Prior to and following surgery, all the patients underwent neuropsychological study after A. R. Luriia (1962). Mnestic disorder was found to be the most common abnormality in patients with AVM at this site. Before surgery, they were detected in 34 of 39 patients, 11 of them having severe memory disorders with the traits of the Korsakoff's syndrome. These patients were found to have mixed posthemorrhagic lesion of the hippocampus, other portions of the temporal lobe and periventricular structures. Twenty nine patients were operated on, 14 of them had progressive mnestic disorder of the modally nonspecific type irrespective the side operated on. There were no postoperative Korsakoff's syndromes. There was no progression in memory defects in patients after surgery on the brain drastically changed after hemorrhage or removal of minor malformations. Before hemorrhage, epileptic paroxysms were observed in 2 of the 39 patients only in the presence of massive AVM obligatorily involving the temporal cortex. Following surgery, there were no new epileptic paroxysms and changes in the emotional status and motivations in the patients. Thus, the hippocampal formation is involved in the primary mechanisms of fixation, retention, reproduction of a memory trace. The participation of many structures of the brain is required to form an emotional status, motivation, and clinical manifestations of epileptic activity.

Adolescent↗

PubMed2004

Effects of beta-hydroxybutyrate on cognition in memory-impaired adults.

Glucose is the brain's principal energy substrate. In Alzheimer's disease (AD), there appears to be a pathological decrease in the brain's ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy.

3-Hydroxybutyric Acid↗

PubMed1992

Encephalitis in cat scratch disease with persistent dementia.

Encephalitis in cat scratch disease is uncommon and usually reversible. The patient with cognitive impairment and severe memory disorder did not improve after a 30 month follow up. MRI revealed disseminated lesions in the white matter of the cerebral hemispheres.

Anti-Bacterial Agents↗