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PubMed1982

Disorders of attention: a frontier in neuropsychology.

There is an extensive behavioural neurological literature on so-called unilateral attentional disorders, but a striking paucity of papers on global disorders of attention, i.e. confusional states. However, confusional states are distinctive because: (1) they are the most common disturbance of the higher functions in clinical practice, by orders of magnitude; (2)they are the only disturbance of the higher functions from which all normal subjects have suffered; (3) they have characteristic clinical manifestations; (4) they are frequently misdiagnosed as progressive dementias, aphasia, memory disorders, and psychoses; (5) they are the only disturbance of the higher functions that commonly cause patients to produce statement that appear to be extremely witty; (6) they can be readily studied experimentally; (7) they are the most common cause of unconcern with or denial of illness. There are almost certainly several different forms of confusional state depending on the aetiology, the rate of development, the age, and the anatomical systems involved, but little classification has yet been carried on. Confusional states are most simply defined as disorders in which there is a loss of the normal coherence of thought or action. Among the striking clinical features are: (1) failure to pay attention, excessive distractibility, or failure to shift attention; (2) paramnesias, i.e. distortions of memory; (3) reduplicative phenomena, 'wild' paraphasias with 'propagation' of error, alterations of mood in many different directions; (4) isolated or predominant disturbance of writing (the most common cause of pur agraphia); (5) unconcern with or denial of illness; (6) apparently playful behaviour. While confusional states are usually attributed to 'global involvement of the brain' as a result of metabolic or toxic disorder, there are in fact many cases produced by focal infarctions inthe right hemisphere, which, in the experience of my department, is one of the commonest effects of cerebrovascular disease. Brief reference is made to the prognosis, and to the theoretical significance for cerebral dominance and the evolutionary development of cerebral dominance in non-human species.

Amnesia↗
PubMed1997

Forgetting from long-term memory in severe closed-head injury patients: effect of retrieval conditions and semantic organization.

This study was aimed at investigating long-term forgetting in chronic survivors of severe closed-head injury (CHI). For this purpose, performance decay passing from a 30-sec- to a 60-min-delay test in four memory procedures (Free Recall of unrelated stimuli, Free Recall of related stimuli. Cued Recall and y/n Recognition) of 20 CHI and 20 normal controls was analyzed. Comparable 30-sec-delay performance in CHI and control patients were obtained by manipulating exposure times to study material during the learning phase. Results demonstrated accelerated forgetting in CHI patients in the Free Recall of the related list only. This finding was particularly evident in CHI patients suffering from a focal temporal lobe lesion. These data are discussed in light of retrieval and encoding deficits characterizing memory disorders in CHI patients.

Adolescent↗
PubMed1998

Ecological validity of list-learning tests and self-reported memory in healthy individuals and those with temporal lobe epilepsy.

We evaluated in patients with temporal lobe epilepsy (TLE) and healthy volunteers whether list-learning tests of episodic verbal/figural memory and subjective self-reports reliably indicate "Memory in Reality" (MIR). MIR was assessed by the incidental memory of the neuropsychological test event one week after testing. Subjective Memory was assessed by a questionnaire (SMQ). Patients achieved poorer results than controls in all measures of memory. Correlation and multiple regression analysis indicates that list-learning is highly predictive regarding performance in MIR. MIR predominantly relied on verbal memory in patients and on visual/figural memory in controls. Subjective memory differentiated patients and controls but it correlated to MIR only in subjects with unimpaired memory. In conclusion, the data indicate a high ecological validity of list-learning paradigms and they seriously question the diagnostic value of self-reported memory. They also indicate that incidentally acquired knowledge might be differentially represented in patients with a memory disorder and healthy persons.

Adult↗
PubMed2003

Neurobehavioral assessment of mood and affect in patients with neurological disorders.

Patients with neurological disorders are particularly susceptible to a variety of affective and mood disorders. Unfortunately, several factors confound the analysis of the individual case. These factors include the fact that neurological deficits may limit the capacity of the individual to communicate mood and feelings. In some cases, the deficits might mimic affective disorders. In this article we will review the traditional presentation of affective disorders in the normal patient. We offer a discussion of specific aspects of the neurobehavioral assessment that might confound the analysis of the individual case. The confounding factors include frontal lobe deficits, aspects of impairments in language, and memory disorders. We also direct attention to motor system deficits and other problems such as sleep disorders that might contribute to a better diagnosis of affective and mood disorders. Finally, we summarize this information and present a general approach for the analysis of the individual.

Anxiety Disorders↗
PubMed1991

L-deprenyl therapy improves verbal memory in amnesic Alzheimer patients.

Altered monoaminergic neurotransmission could play an important role in the cognitive dysfunctions typical of dementia of the Alzheimer type (DAT). DAT is not, however, a homogenous phenomenon inasmuch as two forms are distinguishable: early onset (EO) and late onset (LO). Moreover, focal patterns of neuropsychological deterioration fall into various subgroups. According to our hypothesis, DAT patients, who at the onset of the disease mainly manifest memory disorders, also represent a specific subgroup characterized by impaired cortically projecting catecholaminergic pathways. In a 6-month randomized, double-blind, cross-over study versus placebo we analysed the influence of L-deprenyl on the verbal memory of 19 amnesic EO-DAT patients. Verbal memory was assessed by means of the Rey Auditory Verbal Learning Test. The results obtained show significantly better performances for L-deprenyl treated patients in learning and long-term memory skills. We suggest that L-deprenyl, through selective inhibition of MAO-B and by increasing the activity of the catecholaminergic systems, positively influences cognitive functions and behaviour founded on memory efficiency.

Aged↗
PubMed2005

Spatial working memory and planning ability: contrasts between schizophrenia and bipolar I disorder.

Working memory may be conceptualized as a multi-component system involving the active maintenance and manipulation of stored information in the service of planning/guiding behaviour. Impaired spatial working memory is a robust finding in schizophrenia patients which has been related to an impairment in frontostriatal connectivity. The purpose of this study was to examine the specificity of this impairment by comparing the mnemonic and executive aspects of working memory performance in schizophrenia and bipolar disorder with psychotic features, focusing particularly on the functional dynamics between task components. Twenty-four patients with schizophrenia, 14 patients with bipolar I disorder (manic phase) and 33 healthy control subjects were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB): including the spatial working memory (between search errors and strategy scores) spatial span (storage capacity) and spatial planning (Stockings of Cambridge: accuracy and latency) tasks. Both patient groups were impaired on the spatial span task, which requires the maintenance and retrieval of stored information. In contrast, only schizophrenia patients showed a significant deficit in between search errors, which requires both maintenance and manipulation of information in working memory. That is, they exhibited both a mnemonic and an executive dysfunction. Spatial span was particularly important to accurate planning ability in bipolar patients. In contrast, in patients with schizophrenia poor spatial working memory was a significant predictor of planning impairments, consistent with failures in goal selection, evaluation and/or execution. Furthermore, initial planning time was positively correlated with the latency to complete a planning sequence. This pattern of slow cognitive processing in schizophrenia patients only, resembled that reported previously in patients with basal ganglia disorders. These findings are discussed in terms of a possible common disturbance in fronto-parietal circuitry in the two disorders together with a specific disturbance of fronto-striatal circuitry in schizophrenia, that is not present in bipolar disorder.

Adult↗
PubMed2003

Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790.

RATIONALE: Accumulating evidence suggests a potential role for the 5-HT(6 )receptor in cognitive function and the potential use of 5-HT(6) receptor antagonists in the treatment of learning and memory disorders. OBJECTIVES: The aim of the current study was to investigate the effect of the selective 5-HT(6) receptor antagonist, Ro 04-6790, on both the performance of normal adult rats and restoration of a pharmacological disruption of memory function produced by the non-selective muscarinic receptor antagonist, scopolamine, or the dopamine D(2) receptor antagonist, raclopride, in a rodent model of recognition memory. METHODS: Passive, perceptually based, recognition memory was assessed using a novel object discrimination task. Following habituation to an arena, rats were presented with two identical objects during trial 1 (T(1)) and a novel and familiar object during trial 2 (T(2)). The time spent exploring the two objects in each trial was measured and novel object discrimination assessed in T(2). RESULTS: In the absence of drug all rats spent an equal time exploring the two identical objects in T(1) but more time exploring the novel object in T(2). Scopolamine (but not N-methylscopolamine) and raclopride both produced a dose-dependent reduction in novel object discrimination whilst the 5-HT(6) receptor antagonist, Ro 04-6790, had no effect on discrimination when given alone but completely reversed the scopolamine- but not the raclopride-induced deficit. CONCLUSION: This study demonstrates that acute administration of Ro 04-6790 reverses a cholinergic but not a dopaminergic deficit in a rodent model of recognition memory and provides further support for a role of the 5-HT(6) receptor in the regulation of cognitive function.

Animals↗
PubMed1983

Primary memory and secondary memory in dementia of the Alzheimer type.

Free recall of word lists was investigated in a sample of 47 patients with dementia of the Alzheimer type (DAT) and 31 normal controls of equivalent age and education. Recall was divided into primary memory (PM) and secondary memory (SM) components based on the number of items intervening between presentation and recall. The findings were as follows: (1) the patients showed a greater deficit on the SM than on the PM measure; (2) there was little evidence of proactive interference in the patient group; (3) the PM and SM measures were independent in the controls but not in the patient group; and, (4) the size of patients' PM deficit increased linearly with increasing items between presentation and attempted recall. These results suggest that the memory disorder of DAT is partially the result of defective PM.

Aged↗
PubMed1993

Autopsy in dementing illness: who participates?

The frequency of occurrence of various types of dementing disorders has been ascertained primarily from autopsied series. Since autopsy is voluntary, it is unknown if these series are representative of the entire demented population. To assess this issue, all deaths occurring over a 5-year period in our Memory Disorders Clinic were reviewed, and clinical variables and diagnoses were compared between patients who were autopsied and those who were not. Sixty-nine patients died; 43% (n = 30) underwent autopsy, and 57% (n = 39) did not. Race (no black patients were autopsied), age of disease onset, age of presentation to the clinic, age of death, and interval between last clinic contact and death (significantly less for nonautopsied patients) were found to differ between the two groups. However, clinical diagnosis of dementia was similar in the two groups. The clinical diagnosis was confirmed in 84% of autopsied patients. These results suggest that there are no major differences between clinical diagnoses for autopsied and non-autopsied patients and that the frequency of occurrence of various dementias obtained through autopsied series are representative of the demented population.

Black or African American↗
PubMed1984

Auditory evoked potentials in senescent forgetfulness.

Two evoked potential (EP) techniques and the selective reminding test were employed to investigate an apparently benign forgetfulness in seven elderly subjects and seven age-matched elderly subjects with normal memory. EPs were also recorded in a group of seven young adults. Latency of the P3 component, which has been demonstrated to increase in primary degenerative dementia, displayed the normal age-related variation in both elderly groups, but did not differ between the forgetful subjects and the elderly controls. Further, no difference in the recovery cycle of the EP, as measured in a two tone stimulation paradigm, was present between forgetful and elderly control groups. Reexamination of memory after nearly a year disclosed no evidence of deterioration in either elderly group. These findings suggest that senescent forgetfulness, as defined herein, may be a nonprogressive memory disorder.

Aged↗
PubMed1976

[Participation of the genetic apparatus in memory and learning phenomena].

The first series of experiments showed that inhibition of the proteins synthesis followed by memory disorders, was reflected in decrease of the synaptosomal proteins fraction which was identified as the cholinoreceptor protein. Another series of experiments: training of rats to use unpreferred paw, showed the system acetylcholine-acetylcholinesterase to be directly connected with memory phenomena, and the synthesis of this enzyme to be induced by genetic apparatus. The third series of experiments showed that feeding of rats with small doses of aminoacids for a long time leads to regular shifts in distribution of both the aminoacids and the monoamines. The aminoacids increasing the brain activity were found to activate the production of cycle-adenyl acid. Those aminoacids which inhibit the brain activity, decrease the production of cyclic-AMP. Tranquilizers which decrease the level of monoamines and inhibit the brain activity, also decrease the production of cyclic-AMP. Antidepressants inhibiting MAO and increasing the level of monoamines in the brain, activate the production of cyclic-AMP. As the monoamines act via cyclic-AMP and the latter participates in suppression of DNA, the mechanism of involvement of the genetic apparatus in regulation of memory phenomena and learning, becomes more apparent.

Acetylcholine↗
PubMed1994

Caregiver ratings of personality change in Alzheimer's disease patients: a replication.

Caregivers of 26 patients with Alzheimer's disease (AD) rated current and premorbid personality patterns with the NEO Personality Inventory. Results replicated previous findings on the degree of change reported in a previous group of patients with mixed memory disorder diagnoses. After a diagnosis of AD, the patients were rated as significantly more neurotic, less extraverted, less open, and less conscientious. There were no rated differences of changes in the personality domain of Agreeableness. These results strengthen the usefulness of caregiver ratings of personality change of patients with memory problems who cannot be useful informants on their own behalf.

Aged↗
PubMed2000

Donepezil therapy in clinical practice: a randomized crossover study.

OBJECTIVE: To determine the efficacy of donepezil hydrochloride for the treatment of Alzheimer disease in patients drawn from clinical practice. DESIGN: Two-center, randomized, placebo-controlled, double-masked crossover study. SETTING: Memory disorders units at Massachusetts General and Brigham and Women's hospitals, Boston. PATIENTS: Sixty individuals (30 men and 30 women; mean +/- SD age, 75.0+/-9.5 years) with probable Alzheimer disease and scores of 20 or less on the information-memory-concentration subscale of the Blessed Dementia Scale. INTERVENTIONS: Placebo wash-in, followed in randomized sequence by (1) donepezil hydrochloride therapy, 5 mg/d, for 6 weeks, followed by placebo washout for 6 weeks and (2) placebo treatment for 6 weeks. PRIMARY OUTCOME MEASURE: Change in Alzheimer's Disease Assessment Scale cognitive subscale scores from the beginning to the end of the two 6-week treatment periods. RESULTS: Among patients completing treatment and testing for both periods (n = 48), subscale scores improved (mean +/- SEM) 2.17+/-0.98 points (95% confidence interval, 0.20-4.10 points) during donepezil therapy relative to placebo therapy (P = .04). Scores returned toward baseline within 3 weeks of drug washout. There was no associated change in caregiver-rated global impression (donepezil vs placebo: proportion improved, 0.24 vs 0.22; proportion worsened, 0.27 vs 0.35; P = .34) or on specific tests of explicit memory or verbal fluency. Contrary to studies with tacrine, the presence of the apolipoprotein E epsilon4 allele did not predict donepezil treatment failure. Most common adverse events related to donepezil therapy were nausea (5 patients), diarrhea (3 patients), and agitation (3 patients). Serious events possibly related to drug use were seizure, pancreatitis, and syncope (1 patient each). CONCLUSION: This independent confirmation of data from phase 3 trials suggests that donepezil therapy modestly improves cognition in patients with Alzheimer disease who are encountered in clinical practice.

Aged↗
PubMed1986

Learning and memory disabilities in young adult rats from mildly zinc deficient dams.

Three experiments were conducted to test the behavior of the offspring of rat dams (ZD) fed a mildly zinc deficient diet (10.0 micrograms Zn/g) during pregnancy and lactation. Since zinc deficiency causes anorexia, a second group of rat dams (PF) was fed the same quantity of the diet during gestation and lactation as was consumed by their ZD mates. A third group of rats (AL) was fed the diet ad lib during gestation and lactation. The PF and AL dams were given zinc supplemented (25.0 micrograms Zn/ml) drinking water whereas the ZD dams were given double distilled, deionized drinking water. After weaning, the offspring of all dams were fed Purina Laboratory Chow ad lib until they were 100 days old. The offspring were then reduced to 85% of their ad lib weight and tested on a 17-arm radial maze for memory and learning. In Experiments 1 and 2, the ZD males suffered a significant learning deficit when compared to the AL males. Whereas the PF males suffered a significant learning impairment in Experiment 1, the learning deficit of the PF group was not as severe as the deficit of the ZD group. There was no impairment in reference (long-term) memory for any of the groups. In Experiment 3, significant differences in working (short-term) memory were found among the three groups of females. The ZD group was significantly inferior in working memory when compared to the PF and AL groups. No significant differences in working memory were found between the PF and AL groups.

Animals↗
PubMed2006

[Medication and memory: interactions among the elderly].

Several different systems govern human memory, and different drugs may act specifically on one or more of them. The central nervous system in the elderly is particularly sensitive to drugs, and an iatrogenic cause must be sought for all recent and/or sudden alterations in memory functions. In the case of recent alterations in memory, all nonessential drugs, especially psychotropic agents; should be withdrawn or reduced. Elderly persons, especially those with dementia, are at risk because of the frequent and substantial effects of drugs on their memory: the benefit-risk ratio must be evaluated regularly and essential treatments maintained.

Adrenal Cortex Hormones↗
PubMedDate not supplied

A positive approach to viewing processing deficit theories of amnesia.

This reply is admittedly a defence of the encoding-deficits theory of amnesia. However, it attempts to go further by proposing that this deficit, which was originally designed just to explain amnesics' explicit episodic memory disorder, might be viewed as being but one instance of a more general disorder characteristic of all aspects of amnesic patients' information processing. It is proposed that amnesic patients' inability to perform more consciously controlled conceptual analyses results not only in explicit recall deficits, but sometimes also in instances of below normal implicit memory and recognition ability. Their ability to perform automatic, perceptual-level processing produces normal performance on some implicit and some recognition tasks, but it is not sufficient for all tasks.

Amnesia↗