Working memory performance predicts subjective cognitive complaints in HIV infection

The authors examined the contribution of working memory performance to subjective cognitive complaints in HIV infection beyond the influence of depressive symptoms. Thirty-six adults with HIV infection were administered neuropsychological (NP) tests of working memory, complex psychomotor efficiency, verbal learning, delayed recall, and questionnaires measuring depressive symptoms and cognitive complaints. Working memory performance, depression scores, and complex psychomotor efficiency were most strongly associated with self-reported cognitive complaints, whereas verbal learning scores and simple psychomotor efficiency showed more modest associations. Regression analyses revealed working memory performance to be the strongest NP predictor of self-reported cognitive complaints, comparable with depression scores in the amount of variance explained. These results suggest that working memory performance may be well suited to reflect how patients function in their everyday environment.     

Genuine memory deficits in dementia

Controlled learning with effective cued recall is needed to distinguish between genuine memory deficits due to impairment of specific memory processes and apparent memory deficits due to impairment of other cognitive processes, such as attention, that can limit memory. Effective cued recall is needed for accurate measurement of memory in the elderly because cued recall reveals learning not shown by free recall. When a search procedure was used to control processing for effective encoding and cued recall, nondemented elderly adults recalled all or nearly all 16 items on each trial. Decreased recall by demented patients even after they carried out the same effective processing showed genuine memory impairment that was not due to other cognitive deficits. Cued recall was better than either free recall or recognition in discriminating elderly persons with dementia from those without dementia and by itself accounted for 75 % of the variation in dementia status. Cued recall was especially useful for identifying patients with mild to moderate dementia who were not identified by free recall. It is proposed that elderly persons who have decreased cued recall of a 16‐item list after controlled learning have genuine memory impairment and therefore are likely to be demented because other causes of amnestic syndromes are relatively infrequent in the aged. Controlled learning with effective cued recall should be useful for screening of elderly persons for dementia.     

Recall and recognition memory deficits in depression.

The aim of the present study was to establish the nature of memory deficits of depressive subjects in word learning tests. A word learning test consisting of 1, 3 or 5 learning trials was used. We found that patients were characterized by inferior memory recall compared to controls when 5 learning trials were given. Patients performed significantly slower than controls on a recognition test but both patients and controls recognized the same number of words. This suggests that the memory deficits that are present in many depressive subjects may be restricted to impaired active retrieval from memory. A second experiment revealed that recognition memory and delayed recall as well as immediate recall were impaired in depressive patients after 1 learning trial. These short-comings vanished after 3 trials, except for immediate recall. These data suggest that not only retrieval but also encoding of information into memory may be impaired in depression, especially in the beginning of a task when demands on cognitive effort are high. The results are discussed in terms of resource allocation and demands on effort that may change in the course of a task.     

Verbal memory tests in the differential diagnosis of depression and dementia: discriminative power of seven test variations.

The many tasks for the assessment of verbal memory differ widely in features of presentation and retrieval. In this study, seven common memory tasks (immediate and delayed free recall, randomized presentation, selective reminding, serial recall, recognition after short and long delay) were compared for their discriminative power between depressed, demented, and healthy elderly subjects. Tasks that require little cognitive capacity were hypothesized to be particularly useful to differentiate the patient groups. Demented and depressed patients demonstrated deficits on all tests, the demented being more severe. Only recognition after long and short delay, and delayed recall distinguished demented from depressed patients. Delayed retrieval tasks were more useful to discriminate patient groups than tasks that require little cognitive capacity.     

Variability in memory performance in aged healthy individuals: an fMRI study

Episodic memory performance varies in older subjects but underlying biological correlates remain as yet ambiguous. We investigated episodic memory in healthy older individuals (n=24; mean age: 64.4+/-6.7 years) without subjective memory complaints or objective cognitive impairment. Episodic memory was assessed with repetitive learning and recall of abstract geometric patterns during fMRI. Group analysis of brain activity during initial learning and maximum recall revealed hippocampal activation. Correlation analysis of brain activation and task performance demonstrated significant hippocampal activity during initial learning and maximum recall in a success-dependent manner. Neither age nor gray matter densities correlated with hippocampal activation. Functional imaging of episodic memory thus permits to detect objectively variability in hippocampal recruitment in healthy aged individuals without subjective memory complaints. Correlation analysis of brain activation and performance during an episodic memory task may be used to determine and follow-up hippocampal malfunction in a very sensitive manner.     

Memory complaints; the association with psycho-affective and health problems and the role of personality characteristics. A 6-year follow-up study

BACKGROUND: The objective is to investigate whether memory complaints in older persons without manifest cognitive decline are associated with depressive symptoms, anxiety symptoms, physical health and personality characteristics. Furthermore, it is investigated whether personality characteristics have a modifying effect on the association of memory complaints with depressive and anxiety symptoms and physical health. METHODS: The study was carried out using the Longitudinal Aging Study Amsterdam (LASA). Participants were examined during three observation cycles covering a period of 6 years. They were asked about memory complaints, and were examined on cognitive functioning, physical health, depressive and anxiety symptoms, and the personality characteristics: mastery, perceived self-efficacy and neuroticism. The data were analysed by means of Generalised Estimating Equations (GEE). RESULTS: Memory complaints were associated with physical health problems, depressive and anxiety symptoms, low feelings of mastery, low perceived self-efficacy and high neuroticism. The associations between memory complaints and physical health problems, depressive and anxiety symptoms were significantly stronger in people with high mastery, high perceived self-efficacy and low neuroticism. LIMITATIONS: We used a conservative criterion for cognitive decline and therefore we might have included some people with cognitive decline during our follow-up. In order to minimise selection bias we included actual cognitive performance in our regression models. CONCLUSIONS: Our findings suggest that when older persons complain about their memory and do not show actual cognitive decline, one should be aware that these complaints might reflect psycho-affective or health problems.     

Neurological correlates of depressive symptoms in Alzheimer's disease and vascular dementia.

BACKGROUND: Organic brain disease such as dementia or stroke is associated with depression. In dementia, depressive symptoms are common where there is evidence of vascular disease and in Alzheimer's disease they often coexist with extrapyramidal signs. METHOD: In a study of 60 patients with Alzheimer's disease and 39 patients with vascular dementia, depressive symptoms were rated using the Cornell Scale for Depression in Dementia. Neurological signs were assessed and severity of cognitive impairment was measured with the Mini-Mental State Examination. RESULTS: Depressive symptoms were more severe in vascular dementia. Pyramidal tract signs had no relationship to depression in either type of dementia. In vascular dementia, extrapyramidal and grasp reflexes were strongly related to the severity of depression, and were associated with neurovegetative features. In Alzheimer's disease, extrapyramidal signs were the strongest independent predictor of the severity of depression. CONCLUSION: Depressive symptoms are more severe in vascular dementia compared to Alzheimer's disease and were related to neurological abnormalities.     

Impaired memory consolidation during sleep in patients with functional memory disorder

Functional memory disorder (FMD) is characterized by mnestic and attentional deficits without symptoms of mild cognitive impairment or dementia. FMD usually develops in subjects with high psychosocial stress level and is classified to the somatoform disorders. We assessed memory performance (procedural mirror tracing task, declarative visual and verbal memory task) and other cognitive functions before and after one night of sleep in 12 FMD patients (mean age: 51.7 yrs, 7 females) and 12 healthy subjects matched for age, gender and IQ. Memory performance and other neurocognitive tasks did not differ between the groups at baseline. After one night of sleep, FMD patients showed an impairment of declarative memory consolidation compared to healthy subjects (visual task: p = 0.004; verbal task: p = 0.039). Spectral analysis of sleep-EEG indicated an increased cortical excitation in FMD. We hypothesize that a hyperarousal state in FMD might contribute to sleep disturbance implicating negative effects on declarative memory consolidation.     

A meta-analytic review of mood-congruent implicit memory in depressed mood

In studies of explicit memory, researchers have reliably demonstrated that mood-congruent, depressive information is especially likely to be recalled by individuals exhibiting depressed mood. Results from studies of implicit mood-congruent memory in depressed mood, however, have been largely discrepant. The current research reviews 20 studies of implicit mood-congruent memory for emotionally valenced words in the context of dysphoria and clinical depression. Meta-analytic techniques were used to summarize this research. Results indicated that depressive groups exhibited preferential implicit recall of negative information and nondepressed groups exhibited preferential implicit recall of positive information. Also, depressive implicit mood-congruent memory for negative information was associated with recall and encoding tasks that matched with regard to the perceptual versus conceptual processes required. Furthermore, self-relevance emerged as an important moderator for implicit recall in analyses that compared clinically depressed groups to nondepressed groups. These results provide partial support both for the transfer appropriate processing framework of memory and cognitive theories of depression that emphasize self-relevant information. Finally, certain participant characteristics, particularly age and severity of depressive symptoms, emerged as important moderators of the effect of group status on depressive implicit recall biases.     

Memory complaints as a precursor of memory impairment in older people: a longitudinal analysis over 7-8 years

BACKGROUND: There is considerable dispute about the validity of memory complaints. While some studies find that complaints are an early indicator of dementia or cognitive decline, there are also many studies showing that complaints are more closely associated with negative affect (depression, anxiety and neuroticism). The present paper used three-wave longitudinal data to test three hypotheses: (1) that memory complaints reflect an evaluation of present and past memory performance; (2) that memory complaints predict future memory performance; and (3) that memory complaints predict current and future negative affect. METHODS: A longitudinal study was carried out with a community sample of people aged 70 and over. Participants were assessed for memory complaints, memory performance and negative affect at three waves separated by 3.6 years and 4.0 years. There were 331 persons with data on all relevant variables. The data were analysed using structural equation modelling. RESULTS: Significant paths in the structural model were found from memory performance to future memory complaints, as well as from memory complaints to future memory performance, supporting hypotheses 1 and 2. Memory complaints were associated with current negative affect, but did not predict future negative affect. CONCLUSIONS: Memory complaints do reflect perceptions of past memory performance and are also an early manifestation of memory impairment. However, current negative affect (anxiety and depression symptoms) shows the greatest association with memory complaints.     

Effect of temporal lobe structure volume on memory in elderly depressed patients

Objective

To compare the volume of the hippocampus and parahippocampal gyrus in elderly individuals with and without depressive disorders, and to determine whether the volumes of these regions correlate with scores on memory tests.

Method

Clinical and demographic differences, as well as differences in regional gray matter volumes, were assessed in 48 elderly patients with depressive disorders and 31 control subjects. Brain (structural MRI) scans were processed using statistical parametric mapping and voxel-based morphometry. Cognitive tests were administered to subjects in both groups.

Results

There were no between-group gray matter volume differences in the hippocampus or parahippocampal gyrus. In the elderly depressed group only, the volume of the left parahippocampal gyrus correlated with scores on the delayed naming portion of the visual-verbal learning test. There were also significant direct correlations in depressed subjects between the volumes of the left hippocampus, right and left parahippocampal gyrus and immediate recall scores on verbal episodic memory tests and visual learning tests. In the control group, there were direct correlations only between overall cognitive performance (as assessed with the MMSE) and the volume of right hippocampus, and between the total score on the visual-verbal learning test and the volume of the right and left parahippocampal gyrus.

Conclusions

These findings highlight different patterns of relationship between cognitive performance and volumes of medial temporal structures in depressed individuals and healthy elderly subjects. The direct correlation between delayed visual-verbal memory recall scores with left parahippocampal volumes specifically in elderly depressed individuals provides support to the view that depression in elderly populations may be a risk factor for dementia.     

Medications and verbal memory impairment in schizophrenia: the role of anticholinergic drugs

BACKGROUND: We wished to assess the effect of three types of medication on verbal memory impairments in schizophrenia. METHOD: Forty-eight patients with schizophrenia and 40 healthy control subjects underwent a battery of verbal memory tasks, including free recall, recognition and short-term memory span. All the patients were on antipsychotic medication. In addition, 24 were taking anticholinergic drugs (benztropine) and 30 were taking benzodiazepines. A subsample of 39 had clinical ratings for depressive symptoms. Regression analyses were conducted on the memory measures in this subsample, with negative symptoms, depression, type of antipsychotic medication (conventional v. atypical), benzodiazepines and anticholinergic drugs as predictors. RESULTS: Type of antipsychotic medication made no significant contribution to memory deficits and benzodiazepine use made very little contribution. However, anticholinergic medication was a predictor of memory impairment, especially with regard to semantic organization. Complementary analyses revealed that patients taking any type of drug with anticholinergic activity (benztropine and/or antipsychotic agents) were significantly impaired relative to the other patients on measures reflecting free recall efficiency and semantic organization. CONCLUSIONS: Drugs with anticholinergic activity are the major pharmacological agents that contribute to the verbal memory deficit observed in patients with schizophrenia. These drugs appear to act by impeding semantic organization at encoding.     

Depression, APOE genotype and subjective memory impairment: a cross-sectional study in an African-Caribbean population

BACKGROUND: Subjective memory impairment (SMI) is common in older populations but its aetiology and clinical significance is uncertain. Depression has been reported to be strongly associated with SMI. Associations with objective cognitive impairment are less clear cut. Other factors suggested to be associated with SMI include poor physical health and the apolipoprotein E (APOE) epsilon4 allele. Studies of SMI have been predominantly confined to white Caucasian populations. METHOD: A community study was carried out in a UK African-Caribbean population aged 55-75, sampled from primary care lists. Twenty-three per cent were classified with SMI. Depression was defined using the 10-item Geriatric Depression Scale. Other aetiological factors investigated were education, objective cognitive function, APOE genotype, disablement and vascular disease/risk. The principal analysis was restricted to 243 participants scoring > 20 on the Mini-Mental State Examination (85%). A second analysis included all 290 participants. RESULTS: Depression, self-reported physical impairment and APOE epsilon4 were associated with SMI. The association between SMI and physical impairment was not explained by depression, vascular disease/risk, or disability/handicap. The association between epsilon4 and SMI increased as MMSE scores decreased and was particularly strong in those with depression. The epsilon4 allele was present in 69% (95% CI 41-89%) of those with depression and SMI compared with 28% (20-36%) of those with neither. CONCLUSIONS: Depression may not be a sufficient explanation for subjective memory complaints. Memory complaints in the presence of depression are associated with high prevalence of epsilon4 and therefore, presumably, a raised risk of subsequent dementia.     

Effects of aging and dementia upon recent visuospatial memory

In two experiments, a total of 20 young normals, 29 elderly normals, and 76 elderly demented subjects were administered a computerized delayed visuospatial recall task. Subjects were instructed to remember which room of a 25-room house had a light on in the window. A choice reaction time task was interposed during the delay interval (0–120 seconds) between stimulus presentation and recall. The test was designed to be (1) face valid-relevant to the subjects' everyday lives, (2) sensitive and specific to the cognitive decline associated with senile dementia of the Alzheimer's type (SDAT), and (3) comparable to animal memory tests. Immediate recall of the spatial location of a single stimulus was found to be deficient in severely demented subjects only, and all groups exhibited a decline in recall accuracy with increasing delay intervals. This decline in recall accuracy was greatest in severely demented subjects, smaller in less demented subjects, still smaller in aged normals, and smallest in young normals. No significant forgetting of spatial location occurred between 30 and 120 seconds after stimulus presentation. Increasing stimulus number decreased recall accuracy in all groups and the elderly and elderly demented subjects were more sensitive to the increase in stimulus load than the young normals. Choice reaction time also proved sensitive to age and severity of dementia. Correlation analyses demonstrated that delayed spatial recall (as well as choice reaction time) is highly correltated with clinically evaluated global cognitive status, as well as with tests of verbal recall. These results confirm previous reports that spatial recall is impaired by both age and SDAT. It is concluded that this test procedure and others applying similar approaches should be useful in the assessment of age-related cognitive dysfunction and in the evaluation of potential pharmacological treatments for these disorders.     

Effects of aging and dementia upon recent visuospatial memory

In two experiments, a total of 20 young normals, 29 elderly normals, and 76 elderly demented subjects were administered a computerized delayed visuospatial recall task. Subjects were instructed to remember which room of a 25-room house had a light on in the window. A choice reaction time task was interposed during the delay interval (0–120 seconds) between stimulus presentation and recall. The test was designed to be (1) face valid-relevant to the subjects' everyday lives, (2) sensitive and specific to the cognitive decline associated with senile dementia of the Alzheimer's type (SDAT), and (3) comparable to animal memory tests. Immediate recall of the spatial location of a single stimulus was found to be deficient in severely demented subjects only, and all groups exhibited a decline in recall accuracy with increasing delay intervals. This decline in recall accuracy was greatest in severely demented subjects, smaller in less demented subjects, still smaller in aged normals, and smallest in young normals. No significant forgetting of spatial location occurred between 30 and 120 seconds after stimulus presentation. Increasing stimulus number decreased recall accuracy in all groups and the elderly and elderly demented subjects were more sensitive to the increase in stimulus load than the young normals. Choice reaction time also proved sensitive to age and severity of dementia. Correlation analyses demonstrated that delayed spatial recall (as well as choice reaction time) is highly correltated with clinically evaluated global cognitive status, as well as with tests of verbal recall. These results confirm previous reports that spatial recall is impaired by both age and SDAT. It is concluded that this test procedure and others applying similar approaches should be useful in the assessment of age-related cognitive dysfunction and in the evaluation of potential pharmacological treatments for these disorders.     

A model of verbal memory impairments in schizophrenia: two systems and their associations with underlying cognitive processes and clinical symptoms

BACKGROUND: In a broad cognitive study of schizophrenia we investigated the relationships of verbal memory impairments with cognitive underpinnings on the one hand, and clinical symptomatology on the other. The results have been reported in previous papers. In this paper we show how all these data could be integrated into a consistent pattern of associations. METHOD: Fifty schizophrenic patients underwent a cognitive battery including a verbal memory task with free recall and recognition, a source memory task, and tests of processing speed and selective attention. Ratings for positive, negative and depressive symptoms were available for 40 of the patients. RESULTS: A factorial analysis revealed a distinction between measures of memory efficiency and measures of memory errors. The system of memory efficiency was associated with processing speed and selective attention at the cognitive level, and with depression at the symptom level. The system of memory errors was assumed to be underlain by source-monitoring deficits. These memory errors were increased by positive symptoms and decreased by certain negative symptoms. CONCLUSIONS: All the measures drawn from various memory tasks could be integrated into a model describing their associations with cognitive underpinnings and clinical symptomatology. This model provides a heuristic for the cognitive and pharmacological treatments of verbal memory impairments in schizophrenia, as well as for the understanding of positive symptoms.     

Verbal and nonverbal memory processing in patients with obsessive-compulsive disorder: its relationship to clinical variables

Memory deficits have been reported in several neuropsychological studies of obsessive-compulsive disorder (OCD). Dysfunction in nonverbal memory has been consistently reported, whereas findings on verbal memory are more heterogeneous. The authors studied 50 patients with OCD who were matched for sex, age, educational level, and hand dominance with 50 healthy controls (HC). Cognitive performance in both groups was assessed on verbal and nonverbal memory tasks, and several clinical variables were also assessed in the patient group. Patients with OCD showed a pattern of cognitive dysfunction with alterations in areas of nonverbal memory (recall and recognition), and verbal memory (learning and recall). Older age at onset of OCD was associated with poorer performance on verbal memory tasks. Low scores on some verbal memory tasks were associated with severity of OCD, and nonverbal memory was influenced by depressive symptoms. The study suggests the existence of dysfunction in the execution of verbal and nonverbal memory tasks in OCD; the influence of clinical variables depends on the specific neuropsychological function.     

Amnestic mild cognitive impairment: difference of memory profile in subjects who converted or did not convert to Alzheimer's disease

Episodic long-term, short-term, and implicit memory were investigated in 79 elderly subjects who fulfilled criteria for the amnestic form of mild cognitive impairment (a-MCI; i.e., by having an idiopathic amnestic disorder with absence of impairment in cognitive areas other than memory and without confounding medical or psychiatric conditions) and who developed Alzheimer's disease (AD) after 2 years as well as in 111 subjects affected by a-MCI who did not develop dementia. Results document a memory profile in a-MCI subjects characterized by preserved short-term and implicit memory and extensive impairment of episodic long-term memory. In virtually all episodic memory indexes examined (learning, forgetting, recognition abilities), a-MCI subjects who converted to AD were more severely impaired than were subjects who did not become demented. This memory profile, which closely resembles that exhibited by amnestic patients with bilateral mesial-temporal lobe lesions, confirms a precocious phase in preclinical AD characterized by selective involvement of mesial-temporal areas and worsening of the memory impairment as atrophic changes progress in hippocampal structures. In this context of pervasive episodic memory impairment, tests assessing the free recall of verbal material following a delay interval demonstrated the greater sensitivity to memory deficits of a-MCI subjects who developed AD.     

Memory complaints in a community sample aged 60-64 years: associations with cognitive functioning, psychiatric symptoms, medical conditions, APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities

BACKGROUND: Previous research has found that depression is a major cause of memory complaints. However, there is evidence that memory complaints also weakly predict cognitive decline and dementia. The present study examined a range of possible determinants of memory complaints, covering psychiatric and personality factors, medical history, cognitive test performance, and biological risk factors for dementia (APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities). METHOD: A community survey was carried out with 2546 persons aged 60-64 years living in Canberra and Queanbeyan, Australia. Participants were asked about memory problems which interfered with daily life and whether medical help had been sought. A randomly selected subsample of 476 persons was given a brain MRI scan. RESULTS: Participants with memory complaints were found to have poorer memory test performance, more depression and anxiety symptoms, have higher scores on personality traits involving negative affect, and to have worse physical health. Multivariate analyses showed that measures of cognitive performance did not make a unique contribution to the prediction of memory complaints above that of the other categories of predictors. Those with memory complaints did not differ on any of the biological risk factors for dementia. CONCLUSION: In a community sample aged 60-64 years, memory complaints were most closely related to psychiatric symptoms, personality characteristics and poor physical health. There was no evidence of brain changes indicating early dementia.     

Volume reduction of the entorhinal cortex in subjective memory impairment

To examine the biological basis of subjective memory impairment (SMI), defined as the feeling of memory worsening with normal memory performance, we measured the volume of the entorhinal cortex (EC) and the hippocampus in SMI subjects, patients with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) and healthy controls (CO). Compared with controls, the EC was smaller in the SMI group (left: p = 0.060; right: p = 0.045) and in the other two groups in the following order: CO > SMI > MCI > AD. The same sequence was observed with regard to hippocampal volumes, but the volume reduction of the left hippocampus in the SMI group only reached a trend towards significance (p = 0.072) and the right was not significantly smaller compared with controls (p = 0.37). Compared with controls the average (left/right) volume reduction of the EC was 18% (SMI), 26% (MCI) and 44% (AD). The mean volume reduction of the hippocampus was 6% (SMI), 16% (MCI) and 19% (AD). Our results mirror the temporal sequence of neurodegeneration in AD and support the concept of SMI as the first clinical manifestation of dementia.