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The neurology of memory.

Remembering is an intrinsic and awesome aspect of human function. Memory loss, a common sequela of brain damage, has been studied extensively to understand how the brain encodes, stores and retrieves information. Important anatomic structures for memory have been identified from work in surgical therapy for epilepsy as well as other clinical syndromes where memory loss is a major feature. Beyond clinicoanatomic correlations, current research has focused on synaptic modifications and biochemical processes that underlie changes in neuronal connectivity. As Alzheimer's disease research expands our knowledge of memory, the treatment of other memory disorders will follow.

Brain↗

[Neuropsychological study of long-term cerebral complications of eclampsia (author's transl)].

A review of the literature shows that long-lasting neurological complications of eclampsia are rare, but that, when present, they frequently involve visual function. Two patients are reported, whose symptomatology suggested damage to the posterior region of both cerebral hemispheres. The first patient showed a Balint's syndrome with complete inability to perceive more than one object at a time, erratic gaze movements and optic ataxia. After a year and half a marked improvement was observed. The second patient presented with severe of dyscalculia, spatial memory disorders, constructional apraxia and mild aphasia. She recovered completely in one year. This symptomatology might result from ischemic lesions in the watershed area between the territories of the middle and posterior cerebral arteries, the underlying mechanism being the compression of the posterior cerebral artery against the tentorium, caused by edema.

Adult↗

[Alzheimer's disease and human memory].

Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way with eminently changing memory representations.

Alzheimer Disease↗

Dopamine inhibition and the adaptation of behavior to ongoing reality.

Spontaneous confabulation is a rare memory disorder resulting from orbitofrontal damage or disconnection. Patients act on the basis of memories that do not pertain to the current situation, and are disoriented. No medical treatment is known. Recent studies suggest that subcortical dopaminergic structures are involved in the selection of currently relevant memories. We present a patient who regained the ability to adapt thought and behavior to ongoing reality when treated with risperidone, a dopamine antagonist.

Adaptation, Physiological↗

Homocysteine in neuropsychiatric disorders of the elderly.

OBJECTIVE: There is increasing interest in homocysteine as a risk factor for neuropsychiatric disorders such as stroke, dementia, depression and Parkinson's disease. This article reviews the current literature on the relationship between homocysteine and these disorders to ascertain if any clinical recommendations can be made. METHOD: A MEDLINE and EMBASE search was made for English language publications between 1966 and 2002 using the search terms 'Homocysteine' and 'Stroke', 'Dementia', 'Vascular Dementia', 'Alzheimer's dementia', 'Cognition disorders or cognitive decline or memory disorders', 'Depression or depressive disorders' or 'Parkinson's disease'. In addition, individual articles were hand searched for relevant references. RESULTS: Cross-sectional studies consistently suggest that elevated homocysteine increases the risk of stroke, and may also increase the risk of leukoariosis, vascular dementia (VaD), cognitive impairment and Alzheimer's disease (AD). Longitudinal studies of homocysteine as a risk factor are few and inconsistently supportive of these associations. No intervention trials to determine the effect of lowering homocysteine levels have yet been published. The pathological mechanisms for homocysteine-mediated disease await complete elucidation. Mild hyperhomocysteinemia is common in the elderly population, and folate supplementation can decrease homocysteine levels. CONCLUSION: The epidemiological evidence for homocysteine as a risk factor for neuropsychiatric disease is an emerging area of great interest. Screening the population for hyperhomocysteinemia cannot be recommended at this stage, but individuals at increased risk of cerebrovascular disease or cognitive impairment should be investigated and treated for elevated homocysteine levels.

Aged↗

Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus.

BACKGROUND AND PURPOSE: Neurons with atrophic neurites may remain alive and therefore may have the potential to regenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons. EXPERIMENTAL APPROACH: We investigated the effects of extracts of Astragalus mongholicus on the cognitive defect in mice caused by injection with the amyloid peptide Abeta(25-35). We also examined the effect of the extract on the regeneration of neurites and the reconstruction of synapses in cultured neurons damaged by Abeta(25-35). KEY RESULTS: A. mongholicus extract (1 g kg(-1) day(-1) for 15 days, p.o.) reversed Abeta(25-35)-induced memory loss and prevented the loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with Abeta(25-35) (10 microM) induced axonal atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment with A. mongholicus extract (100 microg/ml) resulted in significant axonal regeneration, reconstruction of neuronal synapses, and prevention of Abeta(25-35)-induced neuronal death. Similar extracts of A. membranaceus had no effect on axonal atrophy, synaptic loss, or neuronal death. The major known components of the extracts (astragalosides I, II, and IV) reduced neurodegeneration, but the activity of the extracts did not correlate with their content of these three astragalosides. CONCLUSION AND IMPLICATIONS: A. mongholicus is an important candidate for the treatment of memory disorders and the main active constituents may not be the known astragalosides.

Amyloid beta-Peptides↗

Group therapy for memory impaired patients: a partial remediation is possible.

BACKGROUND AND PURPOSE: To analyse the prospect of memory training for patients with organic brain damage. METHODS: Sixty-two patients with memory disorder were assigned to three different groups: a control group (n=16) with low dose memory training, a process oriented memory training group (POT) (n=24) and a group (ST) who was taught to compensate for memory problems with different strategies (n=22). Most of the patients had suffered a stroke. Inclusion criteria were medium to weak memory impairment defined by the patients' performance in the California Verbal Learning Test. Patients with complete amnesia were excluded. Specific care was taken that the groups did not differ in age, time since illness, duration of rehabilitation effort, verbal and performance IQ, memory and attention performance. The two treatment groups received 20 hours memory training, the low dose memory training control group 7 sessions. RESULTS: The treatment groups improved in verbal and prospective memory, but only the group with POT experienced a significant improvement compared with the control group. Training effects were specific, i. e. they affected verbal memory, but were not encapsulated, i. e. generalized to the recall of prose passages and of appointments. The POT group also showed a statistically weak outperformance compared with the ST group and some attentional improvement as well. CONCLUSION: Memory training is effective in patients with organic brain lesion, but only if applied frequently. Comparing the two training high intensity treatments, a POT focus seems to be superior to teaching a set of compensation strategies.

Aged↗

Prospects of memory-modifying drugs that target the CREB pathway.

The quest to find safe and effective drugs to treat memory disorders and decline in humans has been aided by the understanding of the molecules underlying memory formation. Studies from vertebrates and invertebrates have identified molecules that are specifically required for converting memories into a long-lasting and stable form. Due to the fact that the activation of the transcription factor cAMP-responsive element-binding protein (CREB) is critical for converting short- to long-term memory, the molecules required for CREB activation and function are potentially important targets for memory-modifying drugs. The progress, prospects, challenges and limitations of drugs targeting the CREB pathway are reviewed here in the context of molecular mechanisms and the biology of memory.

Animals↗

[Memory, aging and Alzheimer's disease].

Memory disorders in elderly can be related to various conditions. The concept of "Age-Associated Memory Impairement" is grounded on a age-related memory deficit in memory testing associated with a memory complaint which is considered as the subjective manifestation of the memory deficit. Actually, memory deficit in objective testing and memory complaints do not appear correlated. Impairment in memory performance is mostly related to neurobiologic brain changes associated with aging or Alzheimer's disease. Conversely, memory complaints are more related to psychosocial factors. However, clinical data and qualitative analysis of the memory disturbances are requested to understand the precise significance of memory deficits in objective testing.

Adult↗

Lifelong corticosterone level determines age-related decline in neurogenesis and memory.

Ageing is accompanied by an alteration of spatial memory, a decline in hippocampal neurogenesis and a dysregulation of the hypothalamic-pituitary axis (HPA) leading to elevated levels of circulating corticosterone. However, the role of the HPA axis in age-related decline in cognitive functions and in neurogenesis decline remains unclear. We found that suppression of glucocorticoids secretion from midlife to the rest of the animals' life increases neurogenesis in old animals and prevents the emergence of age-related memory disorders. Reciprocally, aged rats with a chronic upregulation of the HPA axis exhibit not only spatial memory impairments but also very low levels of hippocampal cell proliferation and survival. Altogether, these results indicate that the extent of lifetime exposure to glucocorticoids determines the extent of age-related decline in hippocampal neurogenesis and consequently age-related cognitive dysfunctions.

Adrenal Glands↗

The effects of bilateral hippocampal damage on fMRI regional activations and interactions during memory retrieval.

Using functional magnetic resonance imaging (fMRI) we examined successful retrieval of real-world memories in a patient (Jon) with selective bilateral hippocampal pathology resulting from perinatal hypoxia compared with healthy control subjects. Jon activated the same brain regions during memory retrieval as control subjects, both medial and lateral on the left. In contrast to controls, Jon also activated many homologous regions on the right. In spite of having 50% volume loss bilaterally in his hippocampi, retrieval in Jon was associated with increased activation of the hippocampi. Furthermore, hippocampal activity, as with the controls, was differential, being most responsive to retrieval of autobiographical events compared with other memory types (autobiographical facts, public events, general knowledge). Jon made a distinction between events that the control subjects did not make, namely that some of the autobiographical and public events he clearly remembered, while others he found that he knew about but did not truly remember. His hippocampi and medial frontal cortex were significantly more active during retrieval of events for which he had clear and conscious recollection compared with those he knew as much about, including the context, but could not remember experiencing. Although Jon activates the same network of brain regions as the controls (albeit bilaterally), and with the same pattern of response in the hippocampus, the communication between regions differs from controls with regard to hippocampal-cortical connectivity. In controls there was increased effective connectivity between parahippocampal cortex and hippocampus, specifically during the retrieval of autobiographical events. In contrast, this increase was not apparent in Jon; rather, retrieval of autobiographical events elicited greater interaction between the hippocampus and retrosplenial cortex, and also increased interaction between retrosplenial and medial frontal cortex. This study underlines the value of scanning patients using fMRI while they undertake tasks they can perform, in this case allowing us to confirm the functionality of remaining tissue in the damaged hippocampi, and to appreciate the neural basis of a distinction (remember/know) that control subjects do not make. Besides refining our knowledge of the hippocampal role in autobiographical event memory, this study indicates that recruitment of bilateral regions during memory retrieval, and altered patterns of effective connectivity between brain regions may be important indicators of disordered memory.

Adult↗

Validity of informant reports about AD and MCI patients' memory.

Efficient, valid, and economical methods are needed to measure memory in elderly patients who are participants in clinical trials for the prevention or treatment of dementia. Data provided by knowledgeable informants are an ideal means of assessment, but factors that may limit the validity of informant-report data are not known. This study investigated the living status, relationship type, and educational history of informants and determined the impact of these factors on the validity of informant-report data about patients (N = 62) diagnosed with Alzheimer disease or mild cognitive impairment. Validity of informant-reported memory was indicated by the correlation between the reports and patients' performance on a neuropsychological memory test. Results indicated that informants who lived with patients provided more accurate reports of the patients' memory than informants who did not live with the patient. Spouses were more accurate than other relationship types, although relationship type was confounded with living status. Patient education and neuropsychiatric symptoms were not significantly associated with informant accuracy. Results of this study will aid in selecting informants who can provide the most accurate data about memory disorder patients and will aid in the development of protocols for clinical trials for dementia prevention and treatment.

Aged↗

Lateralization of deficit in self-awareness of memory in patients with intractable epilepsy.

PURPOSE: Memory disorders are prominent among patients with intractable epilepsy. It has, however, been frequently observed that subjective memory complaints of these patients did not match their performance on objective memory tests. This discrepancy may reflect emotional, cognitive, or self-awareness deficits among these individuals. The aim of the current study was to explore the interference of cerebral dysfunction on accuracy of self-appraisal for memory. METHODS: The degree of concordance between self-perception of memory function, as measured by a visual analogue scale, and actual performance on memory tests was computed in 35 patients who were candidates for epilepsy surgery and demographically matched normal control subjects. The difference between the self-estimated memory ability and performance on memory tests and its relation to the laterality of an epileptogenic lesion, cognitive factors, and affective status was then examined. RESULTS: The results show that the discrepancy between the self-estimated memory ability and performance on memory tests in patients with right hemisphere epileptogenic lesions was significantly larger in magnitude compared with that in patients with left hemisphere lesions and demographically matched control subjects (p = 0.001). Furthermore, whereas patients with left hemisphere lesions and normal controls had about an equal number of positive and negative discrepancy scores, all patients with right hemisphere lesions had positive discrepancy scores, suggesting a tendency for overestimation of memory abilities. CONCLUSIONS: These results suggest that right hemisphere lesions may introduce a systematic bias in self-awareness for memory. This bias may color patients' perceptions of self and others, affecting their perceptions of the quality of life, and necessitating an adjustment of the treatment goals and procedures.

Adolescent↗

Memory impairment in Korsakoff's psychosis: a correlation with brain noradrenergic activity.

The concentration of the primary brain metabolite of norepinephrine is diminished in the lumbar spinal fluid of patients with Korsakoff's syndrome. The extent of its reduction is significantly correlated with measures of memory impairment for individual patients. These data suggest that the memory disorder of Korsakoff's syndrome may result from damage to ascending noradrenergic pathways by the diencephalic and brainstem lesions associated with this disease.

Alcohol Amnestic Disorder↗

The etiology and neuropathology of alcoholic Korsakoff's syndrome. Some evidence for the role of the basal forebrain.

Recent neuropsychological and neuropathological investigations with long-term alcoholics suggest that the etiology and neuropathology of the Wernicke-Korsakoff syndrome are more complex than previously believed. Although problem-solving and visuoperceptual deficits seem to develop slowly during decades of alcoholism, the amnesic symptoms associated with Korsakoff's syndrome may appear acutely when severe malnutrition and alcoholism are combined. Furthermore, the report that alcoholic Korsakoff patients, like patients with Alzheimer's disease, have endured a substantial neuronal loss in structures comprising the basal forebrain suggests a role for this brain region in the alcoholic patients' amnesic syndrome. Some initial demonstrations of similarities in the memory disorders of alcoholic Korsakoff and Alzheimer patients indicate that Korsakoff's syndrome may be accurately characterized as a "basal forebrain" as well as a "diencephalic" amnesia.

Alcohol Amnestic Disorder↗

Do patients with panic disorder show a memory bias?

BACKGROUND: Cognitive models of panic disorder are becoming more and more influential. Therefore, research specifying cognitive processes related to panic disorder is needed. The present study investigated memory bias for panic-related material in patients with panic disorder. METHODS: Memory bias for panic-related material was investigated experimentally by a memory task requiring classification of panic-related and non-panic-related words. Sixty patients with panic disorder and 60 controls with no diagnosis of a mental disorder participated in the study. RESULTS: As expected, panic patients showed smaller differences in the time needed for classification of panic-related versus non-panic-related material than controls. CONCLUSIONS: Patients with panic disorder show a memory bias for panic-related material when conceptual implicit recall is required. In order to clarify whether this bias is involved in the maintenance of the disorder, it seems important to investigate whether the bias is still present after successful therapy.

Adolescent↗

Pharmacology of the memory process.

Rather than reviewing once again the published literature on drugs which are capable of modifying the memory process, the authors stress the methodological difficulties which impede the development of such products. At the moment, substances which act on neurotransmission systems, and in particular cholinergic and gabaergic agents, seem to be good candidates. The choice of the molecule to be studied in man depends on the neurochemical physiopathology of the memory disorder which one seeks to correct. For this reason, one tries to select an animal model of memory which is closest to the clinical situation pertaining to man on which the tested molecule might act favorably.

Animals↗

[Learning disorders after ruptured aneurysms of the anterior communicating artery].

The aim of this study was to reevaluate short term and long term memory disorders after anterior communicating artery rupture, then to more specifically assess the importance and the role of forgetting, proactive and retroactive interferences, impaired memory for temporal order, attention disorders and dysexecutive syndrome, and finally MRI-defined brain lesions. Twenty one patients presenting with selective anterior brain injury, were assessed at the secondary and late post stroke phases. The short term memory analysis showed the digit span was reduced at the secondary stage, but that mean performances were preserved in the Peterson and Sternberg paradigms. Verbal and visuospatial learning in long term memory showed a severe deficit in free recall, chiefly serial, and associative recall. Recognition was mildly impaired at the secondary phase, and later normalized. A definite and lasting increase of proactive and retroactive interferences and an impairment in discriminating the temporal order of word presentations were observed. Amnesic impairment was relatively well correlated with forgetting, severity of interferences and temporal order amnesia, so as with disorders of attention and executive functions (Wisconsin Card Sorting Test). However, intrusions in free recall and false recognitions were not clearly related with the dysexecutive syndrome. The severity of amnesia was associated with lesions of the left anterior cingulate cortex, and of the corpus callosum. These results suggest that these patients mainly had a deficit in information retrieval, mostly compromising long term memory, but also to a lesser degree short term memory. Forgetting, interferences and the dysexecutive syndrome probably play an important role in the decline of mnemonic performance, but do not clearly explain intrusions in recall and errors in recognition.

Aged↗