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[Memory disorders in the elderly: complementary examinations--for whom?].
Recognizing the existence of memory disorders in elderly subjects necessarily involves developing a diagnostic strategy to identify the causes. Three types of complementary investigation are available: neurophysiological and neurobiological tests, and anatomical and functional brain imaging studies. Major efforts have been made to identify diagnostic markers on the electroencephalogram. Quantified EEG may have a certain value. However, it provides a plethora of data and there is no consensus on which items are most relevant on the EEG, whether the patient is awake or asleep. Evoked 'cognitive' potentials may also provide useful data, particularly to distinguish between the different types of degenerative dementia. Exaggerated pupil dilation in response to a mydriatric drug has also been put forward as a diagnostic test. The results, however, are controversial. For the time being there is no diagnostic laboratory parameter that can be used routinely, even if studies of the proteins tau and P97 are promising. Molecular genetics-based studies have identified a number of chromosomal abnormalities in certain families. Apart from studies of chromosome 19 and apolipoprotein 3, these markers have no practical utility. Allele sigma 4 is associated with a higher risk of Alzheimer's disease. Apolipoprotein E phenotyping can of course be of diagnostic value, but no more so than neuropsychological or neuroimaging methods. On the other hand, it is difficult to derive a predictive test. It also seems difficult to develop a diagnostic strategy without including brain imaging studies. The value of morphological imaging (CT, MRI) in the diagnosis of dementias is clear. Volumetric measurements of certain brain structures might be a useful diagnostic approach for early detection. Functional brain imaging methods (PET and SPECT) appear particularly suited to the diagnosis of degenerative dementias. The presence of functional abnormalities at onset, and, even before the first clinical signs appear, is clearly valuable.
[Drug evaluation of huperzine A in the treatment of senile memory disorders].
Huperzine A is an alkaloid which was first isolated from Huperzia serrata (Thumb) Trev by Zhejiang Academy of Medical Sciences and Shanghai Institute of Materia Medica, Chinese Academy of Sciences. It exhibits a significant anticholinesterase activity and has been used on myasthenia gravis patients. The therapeutic effects were studied by random, match and double-blind method on 56 patients of multi-infarct dementia or senile dementia and 104 patients of senile and presenile simple memory disorders. The curative effects were evaluated by Wechsler memory scale. The im dose for multi-infarct dementia was 0.05 mg bid for 4 wk, whereas that for senile and presenile simple memory disorders was 0.03 mg bid for 2 wk. Saline was used on control group. The result showed that the curative effect of huperzine A was significant. Only a few patients felt slight dizziness and this did not affect the therapeutic effects.
Precision and accuracy of subjective time estimation in different memory disorders.
The aim of this study was to evaluate how different memory disorders affect subjective time durations. For this purpose we studied prospective time estimations in 4 amnesic (A) and in 15 Alzheimer's disease (AD) patients, and compared their performance with that of 5 matched young normal controls (YC) and 15 elderly subjects (EC). For the short-time durations we asked the subject to repeatedly reproduce a standard interval of 1 s. To test how subjects evaluated longer time durations, we choose a verbal estimation procedure. The subjects' task was to read either 5, 10, 20, or 40 digits appearing one at a time, while concurrently keeping the rhythm of 1 key press per second. At the end of each sequence, subjects had to judge the elapsed time from the beginning of the trial. Results showed that amnesics can correctly reproduce 1-s intervals. However, their accuracy of verbal estimates of longer durations was severely impaired. AD patients showed increased variability on repeated reproduction of 1-s intervals and were both inaccurate and imprecise in their verbal estimate of longer durations. Using the framework of the Scalar Timing Model, we conclude that amnesic patients exhibit a deficit in encoding and storing the current time for intervals that exceed their short-term memory range, while AD patients show a pattern of deficit that is explained by a more widespread involvement of both the clock, the memory, and the decisional mechanisms.
Long-term retention of computer learning by patients with memory disorders.
Previous research has demonstrated that patients with memory disorders resulting from closed-head injury can acquire the complex knowledge and skills necessary for the use of a microcomputer. The present paper extends the generality of those findings by showing that (1) amnesic patients with other etiologies could similarly learn how to operate a computer and (2) the knowledge and skills acquired were retained over intervals of up to 9 months.
Selective preservation of memory for people in the context of semantic memory disorder: patterns of association and dissociation.
A number of single cases in the literature demonstrate that person-specific semantic knowledge can be selectively impaired after acquired brain damage compared with that of object categories. However, there has been little unequivocal evidence for the reverse dissociation, selective preservation of person-specific semantic knowledge. Recently, three case studies have been published which provide support for the claim that such knowledge can be selectively preserved [Kay, J., & Hanley, J. R. (2002). Preservation of memory for people in semantic memory disorder: Further category-specific semantic dissociation. Cognitive Neuropsychology, 19, 113-134; Lyons, F., Hanley, J. R., & Kay, J. (2002). Anomia for common names and geographical names with preserved retrieval of names of people: A semantic memory disorder. Cortex, 38, 23-35; Thompson, S. A, Graham, K. S., Williams, G., Patterson, K., Kapur, N., & Hodges, J. R. (2004). Dissociating person-specific from general semantic knowledge: Roles of the left and right temporal lobes. Neuropsychologia, 42, 359-370]. In this paper, we supply further evidence from a series of 18 patients with acquired language disorder. Of this set, a number were observed to be impaired on tests of semantic association and word-picture matching using names of object categories (e.g. objects, animals and foods), but preserved on similar tests using names of famous people. Careful methodology was applied to match object and person-specific categories for item difficulty. The study also examined whether preservation of person-specific semantic knowledge was associated with preservation of knowledge of 'biological categories' such as fruit and vegetables and animals, or with preservation of 'token' knowledge of singular categories such as countries. The findings are discussed in the context of a variety of accounts that examine whether semantic memory has a categorical structure.
[Memory disorders in lesions of the thalamus in man].
Isolated memory disorders occur after bilateral involvement of thalamus. Anterograde amnesia is not complete; retrograde amnesia is always severe. Four groups of thalamic nuclei may be affected: anterior nuclei; midline nuclei, medialis dorsalis nuclei; intralaminar nuclei. A pathophysiologic interpretation is proposed. Three kinds of memory processes may be involved: consolidating process that leads to the formation of memory traces (anterior nuclei, midline nuclei); retrieving process that leads to the activation of memory traces (intralaminar nuclei); temporal organizing process that regards ancient et recent memory traces (medialis dorsalis nuclei).
The relationship between working memory and episodic memory disorders in transient global amnesia.
In a previous study, we investigated the relationship between the disorders of both episodic memory and working memory in the acute phase of transient global amnesia (TGA). Since executive functions were spared, another dysfunction may be responsible for the binding and maintenance of multimodal informations and contribute to the encoding disorders observed in some patients [Quinette, P., Guillery, B., Desgranges, B., de la Sayette, V., Viader, F., & Eustache, F. (2003). Working memory and executive functions in transient global amnesia. Brain, 126, 1917-1934.]. The aim of this present study was to assess the functions of binding and maintenance of multimodal information during TGA and explore their involvement in episodic memory disorders. We therefore conducted a more thorough investigation of working memory in 16 new patients during the acute phase of TGA using two tasks designed to assess the binding process and both dimensions of the maintenance, namely the active storage and the memory load ability. We also investigated the nature of the episodic memory impairment in distinguishing between the performance of patients with preferential encoding deficits and those of patients with preferential storage disorders on the episodic memory task. This distinction was closely related to the severity of amnesia, i.e. an encoding disorder was observed rather in the early phase of TGA. The results showed that while the functions of binding and maintenance of multimodal information were intact in patients with storage disorders, they were impaired in the case of encoding deficits. These results are interpreted in the recent framework of episodic buffer proposed by Baddeley [Baddeley, A. D. (2000). The episodic buffer: A new component of working memory? Trends in Cognitive Sciences, 4, 417-423] that represents an interface between working memory and episodic memory.
Relation between informant-rated personality and clinician-rated depression in patients with memory disorders.
OBJECTIVE: The goal of this study was to examine the convergent validity of informant-rated changes in depressive and related personality traits with clinician-assessed depression in memory-disordered patients. BACKGROUND: Depressive symptoms are frequent complications in persons with dementias such as Alzheimer disease, and caregiver informants consistently report changes in depression and related neurotic traits on the NEO Personality Inventory (NEO-PI) in dementia patients. METHODS: In 78 patients undergoing evaluation of memory complaints at an Alzheimer disease clinic, depression was characterized by clinical diagnosis, a clinician-rated scale, and informant ratings of premorbid versus current depression, anxiety, vulnerability, and neuroticism on the NEO-PI. RESULTS: The diagnostic groups differed in meaningful patterns on the NEO-PI measures. Those with a diagnosis of major depression differed from never-depressed patients in all personality areas, although those with depressed mood differed only on NEO-PI depression. The clinician-rated depression scale correlated modestly with current personality and change from baseline personality. CONCLUSIONS: The NEO-PI provides a useful measure of informants' perspectives on depressive personality changes in patients with memory disorders but does not correspond fully with a clinical syndrome of depression.
[Rehabilitation of memory disorders: objectives, strategies and evaluation].
Memory rehabilitation can be proposed to amnesic patients with mild or moderate isolated memory deficit and with some preserved memory components. It is necessary to study memory with global psychometric tests, specific memory examination and pragmatic study, and to have definite memory aims. The facilitating effects of mental imagery and mnemonic strategies, preserved learning and compensatory aids were analysed.
Age-dependent alterations in hippocampal synaptic plasticity: relation to memory disorders.
In this paper, we review the evidence indicating that the common disturbance in recent memory associated with aging is a consequence of functional and structural impairment in the hippocampal formation. In the Fischer 344 rat, an experimental model of the human age-related memory disorder was developed. The majority of aged rats of this strain show impaired performance in the 8-arm radial maze in a manner typical of young rats with bilateral hippocampal lesions. Aged animals also exhibit rapid decay of LTP and slower kindling of the perforant path-dentate synapse. Furthermore, quantitative morphometric analysis of the hippocampal synaptic architecture revealed that aged, memory-impaired rats had a specific loss of perforated axospinous synapses in the middle third of the dentate gyrus molecular layer; the extent of loss was directly related to the degree of memory dysfunction. Most important was the fact that the electrophysiological and morphological abnormalities did not appear in equally old animals with good memory.
Evidence that mnesic states govern normal and disordered memory.
Although it is recognized that retrieval may be state-dependent, only recently has a paradigm been identified that allows state-dependence in rats to be demonstrated reliably and at relevant doses of CNS agents. In humans, the effects of scopolamine constitute a valuable model of disordered memory. We used this paradigm to analyze the effects of scopolamine on different memory processes. Rats treated with either saline or 0.01-10 mg/kg doses of scopolamine learned to lever press for milk reward, and were then tested for retrieval while given the same or a different treatment. Saline-to-scopolamine as well as scopolamine-to-saline state changes produced robust failures to retrieve the response. Remarkably, the state produced by 2.5 mg/kg scopolamine, like that produced by saline, produced little intrinsic effect on learning or any other memory process (i.e. when the prevailing state was left unchanged). However, changing the implemented state from one to the other between two different processes, disrupted not only retrieval, but also learning, encoding and retention. We also determined whether the graded state changes produced by 0.01-10 mg/kg doses of scopolamine could mimic the peculiar and poorly understood temporally graded retrograde amnesia that occurs in Alzheimer's disease. In rats that had acquired a complex drug-discrimination task over a 6-month period, scopolamine-induced state changes seemed to produce dose-dependent deficits in the retrieval of recent information while preserving those abilities that had been acquired in the increasingly remote past. Beyond its role in retrieval, the findings implicate state dependence in learning, encoding and retention, and suggest that physiologically defined mnesic states govern each of these. The changes of mnesic state that are likely associated with excessively labile cholinergic neurotransmission may conceivably cause the complex disabilities of Alzheimer's disease.
An outline for the analysis of dementia. The memory disorder of Huntingtons disease.
Methods have been developed for assessing the cognitive parameters contributing to a memory disorder. Our findings suggest that individuals with Huntington disease have impairments in the encoding of new information and the consistent retrieval from storage of learned material. Their difficulties lie particularly in the realm of episodic memory.
Treatment of memory disorders in epilepsy.
Impaired memory is a common and often debilitating complaint in patients with epilepsy. Overlapping variables such as seizure control, attentional dysfunction, and mood disorders further complicate diagnosis and management. Direct therapy for memory deficits associated with epilepsy is rarely attempted. The varied pharmacological (AED selection, cholinesterase inhibitors, stimulants, antidepressants, and herbal supplements) and nonpharmacological approaches to cognitive remediation in epilepsy patients are reviewed.
Development of the St. George Hospital Memory Disorders Clinic Occupational Therapy Assessment Scale.
The St. George Hospital Memory Disorders Clinic Occupational Therapy Assessment Scale (OTAS) is a performance-based assessment of activities of daily living (ADL) administered in the home environment to monitor function among patients with early cognitive decline. Of the 30 items investigated, 19 items that measured "higher" functional domains were found to be useful in discriminating between subjects. Psychometrically, these 19 items had high internal consistency (coefficient alpha = .89) and high interrater reliability (kappa coefficient range: .71-1.0), and correlated well with other measures of higher function (Lawton's instrumental activities of daily living scale: r = .75; Nottingham extended ADL scale: r = .67). However, unlike these latter measures, the OTAS also correlated well with the Mini-Mental State Examination (r = .73), indicating that OTAS is a valid instrument that should be sensitive to functional problems among patients in the early stages of cognitive impairment.
Protein kinase A as a therapeutic target for memory disorders: rationale and challenges.
cAMP-dependent protein kinase A (PKA) signaling has a key role in memory processes and has been identified as a potential therapeutic target for memory disorders. The activation of PKA signaling is crucial for the consolidation of long-term memories dependent on the hippocampus and/or the amygdala, By contrast, initial studies indicate that cAMP-PKA activation might impair the working memory and executive functions of the prefrontal cortex. Furthermore, PKA activation in the nucleus accumbens might increase sensitivity to addiction. These complexities must be heeded when designing medications aimed at altering PKA activity. PKA might be most practical as a therapeutic target in disorders with global alterations in cAMP-PKA activity due to genetic or environmental factors.
The detection of exaggerated or simulated memory disorder by neuropsychological methods.
Some neuropsychological tests devised to detect exaggeration and simulation of memory disorder are reviewed with reference to models of memory and our current knowledge of the behaviour of amnesic patients. These tests are based on the assumption that naive simulators or exaggerators do not know either that amnesic patients can perform them normally, or near normally, or that subjects can only fail them by deliberate suppression of the correct response. It is concluded that several such tests show promise and are worthy of further development.
Hearing loss in a memory disorders clinic. A specially vulnerable population.
OBJECTIVES: To determine the prevalence and characteristics of hearing loss in patients undergoing examination because of a memory disorder, to determine whether currently used screening tools were adequate for use in this specific population, and to determine if patients with Alzheimer disease reliably report hearing problems. DESIGN: Case-control study. PATIENTS: A consecutive sample of 52 patients: 30 patients who met the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease (group 1) and 22 patients with other forms of cognitive impairment (group 2). METHODS: Patients underwent a hearing screening that included a case history, a visual inspection of the external ear canal and tympanic membrane, and pure tone audiometry. Patients and their caregivers completed a questionnaire intended to assess hearing impairment and perceived disability. OUTCOME MEASURES: Pass or fail on pure tone audiometry and pass or fail on a hearing impairment questionnaire. RESULTS: Of the 52 patients, 49 had significant hearing loss. No difference was found in the failure rate between patients in groups 1 and 2. In group 1, a significant discrepancy was found between the patient's self-report and that of their caregivers, whereas in group 2, the self-report was reliable. The prevalence of hearing loss in this population greatly exceeds the prevalence in healthy aged controls. CONCLUSION: The extraordinarily high prevalence of hearing loss in this selected population suggests that a hearing evaluation should be part of any assessment of cognitive function.