Development of neuropsychological deficits in Huntington's disease

Patients with more recently diagnosed Huntington's disease (RHD) were compared on a neuropsychological test battery with patients who had had the disease one to eight years (moderate HD) and with asymptomatic offspring. Though the patients with HD showed deficits in motor and motor-independent abilities, the patients with RHD were less impaired on factors assessing visuospatial ability, cognitive flexibility, and motor steadiness. Of particular interest was the finding that some asymptomatic offspring showed deficits in visuospatial ability and auditory memory that resembled the deficits of patients with RHD. The findings suggest that deficits in HD do not develop at a uniform rate; deficits in cognitive flexibility occur in later stages of the disease; and visuospatial and auditory memory deficits are very early signs and are present in some asymptomatic offspring.     

Regional cerebral blood flow and cognitive function in Huntington's disease and schizophrenia. A comparison of patients matched for performance on a prefrontal-type task

Matching patients with etiologically distinct but clinically overlapping cognitive disorders on performance of a regionally specific neuropsychological task is a novel and potentially powerful approach to highlighting differences in the pathophysiological mechanisms of impaired cognition. We used this strategy to compare patients with Huntington's disease (HD) and schizophrenia (SC), disorders that share similarities in cognitive impairment. Patients were matched on the basis of performance on the Wisconsin Card Sorting test of "prefrontal" function, after which neuropsychological test data and regional cerebral blood flow data were determined while patients who performed the Wisconsin Card Sorting test were examined. Patients with HD performed worse on visuospatial tasks and recall memory than did patients with SC, although Wechsler Adult Intelligence Scales-Revised IQ and Wechsler Memory Scale memory quotients were equivalent. These differences could not be attributed to differences on the index task, the Wisconsin Card Sorting Test. Patients with HD and SC exhibited a double dissociation in regional cerebral blood flow. The patients with SC had relatively low frontal and high parietal flows, while patients with HD exhibited the reverse of this pattern. Thus, the regional cerebral blood flow and neuropsychological findings in this study appeared to demonstrate that the single final common cognitive impairment of executive function in HD and SC is associated with two markedly dissimilar pathophysiological states.     

Memory functioning in familial bipolar I disorder patients and their relatives

Objective: The aim of this study was to compare the memory function of patients with familial bipolar I disorder (BD I) who had shown psychotic features, their non‐psychotic, non‐bipolar first‐degree relatives, and normal controls. Method: We assessed 38 patients with a lifetime diagnosis of BD I who had experienced psychotic symptoms, 49 of their non‐psychotic, non‐bipolar first‐degree relatives, and 44 controls. Patients and relatives were from families multiply affected with functional psychotic illness. A five‐subtest short form of the Wechsler Adult Intelligence Scale–Revised and three Wechsler Memory Scale subtests were administered to all participants. Results: BD I patients showed deficits in verbal memory and verbal learning but not in visual memory. Compared to controls, relatives showed worse verbal learning at a statistically significant or suggestive level and performed significantly worse in both immediate and delayed verbal memory. Similar to patients, there were no differences between the relatives and control group for visual memory. Conclusion: Impaired verbal memory and learning were found in patients and their relatives. These deficits may represent candidate endophenotypic markers for bipolar disorder.     

Do memory complaints represent impaired memory performance in patients with major depressive disorder?

Memory complaints are found to be associated with depression. However, the question is, “How much these subjective complaints indicate objective memory impairments?” The aim of this study is to determine whether subjective memory complaints represent objective memory impairments and to establish the demographic and clinical characteristics of patients with major depressive disorder (MDD) and subjective memory complaints. Sixty‐four patients with MDD were assessed for objective memory performance through subtests of the Wechsler Memory Scale‐III. Memory complaints also were assessed in these patients with a structured interview. Thirty healthy controls were also included in the study to compare memory performance among groups. The Hamilton Rating Scale for Depression was used to measure the severity and characteristics of depression. Patients with MDD who had longer duration and earlier onset of depression reported more memory complaints. MDD patients with memory complaints had more hypochondriac concerns but not more depression severity compared with those without memory complaints. There was no relationship between subjective memory complaints and objective memory performance in MDD patients. Patients with MDD with and without memory complaints had lower scores on the Wechsler Memory Scale‐III than the control group. Subjective memory complaints are not a valid indictor of objective memory impairments, and the diagnostic value of self‐reported memory is being questioned in patients with MDD. The cognitive status of MDD patients should be assessed routinely, regardless of the patient awareness of his or her cognitive deficits. Depression and Anxiety, 2008. © 2007 Wiley‐Liss, Inc.     

Cognitive impairments in cerebellar degeneration: a comparison with Huntington's disease

To determine the specificity of cognitive impairments in patients with cerebellar degeneration (CD), the neuropsychological test performance of 31 CD patients was compared to that of 21 patients with Huntington's disease (HD) and 29 normal adults. The CD and HD groups did not differ in age, education, or duration of illness, and their overall severity on a quantified neurological examination was similar. Fifteen neuropsychological test variables were reduced to five underlying domains: motor, verbal, spatial, memory, and executive functioning. The CD patients had their greatest impairment in the executive domain and their least in the memory domain. In contrast, the HD patients had very substantial spatial deficits and significant memory impairment, in addition to executive dysfunction. The findings indicate that 1) the cognitive impairment in CD is not as severe as in HD, and 2) the pattern of deficits in CD, while consistent with a subcortical dementia, differs in important ways from that in HD. These differences may reflect the involvement of the cerebellar dentate nucleus and the striatal nuclei in separate "loops" or closed circuits, linking them with specific areas of cerebral neocortex.     

An assessment of verbal recall, recognition and fluency abilities in patients with Huntington's disease

Two investigations concerned with the memory deficits of patients with Huntington's Disease (HD) were performed. In the first experiment, early and advanced HD patients showed superior recognition memory than did alcoholic Korsakoff patients on modified recall and recognition forms of the Rey Auditory Verbal Learning Test. In contrast, on a letter fluency test (FAS) requiring the patients to search their semantic memories, both HD groups produced fewer correct words and perseveration errors than did the alcoholic Korsakoff group. In the second experiment, HD patients and Korsakoff patients were compared in their and recognition of short passages. While the HD and Korsakoff patients were equally impaired on recall tests, the HD patients evidenced significantly better recognition memory than did the amnesic group. As on the fluency test, the prose of the Korsakoff patients was characterized by intrusion (i.e., perseverative) errors. The results of the two experiments indicate that HD and Korsakoff patients' memory deficits are related to deficiencies in retrieval and an increased sensitivity to proactive interference, respectively.     

Cognitive functioning in depersonalization disorder

Depersonalization disorder (DPD) is a dissociative disorder characterized by a subjective sense of unreality and detachment, and has been associated with deficits in perception and short-term memory. In this study, 21 DPD and 17 healthy comparison participants free of psychiatric disorders were administered a comprehensive neuropsychologic battery. The groups did not differ in full-scale, verbal, and performance IQ (Wechsler Adult Intelligence Scale), in working memory (Paced Auditory Serial Addition Test), or in selective attention (Digit Span with Distracters). The DPD group performed significantly worse on immediate visual and verbal recall (Wechsler Memory Scale, Revised), but not on delayed recall. Dissociation severity was significantly correlated with processing slowness and distractibility. We conclude that DPD is associated with cognitive disruptions in early perceptual and attentional processes.     

Discrepancies between IQ and memory scores in alcoholism and aging

Standardized IQ and memory tests were administered to 30 alcoholic men (7 with Korsakoff's syndrome) and 29 nonalcoholic controls between 24 and 74 years of age, in order to evaluate alcohol-related discrepancies between IQ and memory scores (including those attributable to possible premature aging). Severity of amnesia often has been defined operationally as a large discrepancy between IQ scores on the Wechsler Adult Intelligence Scale (WAIS), and scores on memory tests such as the Wechsler Memory Scale (WMS). In the context of a normal WAIS Full Scale IQ or Verbal IQ, a low WMS memory quotient (MQ) signals the possibility of anterograde memory disorder. Revised and nonrevised versions of the WAIS and WMS were given to all of the subjects. As expected, the revised versions yielded lower scores than the non-revised versions; these differences were especially prominent in the older subjects (whether or not they had a history of alcoholism) and the Korsakoff patients. Korsakoff patients demonstrated the largest discrepancies between IQ and memory scores, regardless of the tests being used. Results indicated that measures used clinically to reveal amnesia, that is, large differences between IQ scores and memory scores, were effective in any combination (the WAIS or the WAIS-R with the WMS or the WMS-R).     

Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD

BACKGROUND: Frontotemporal dementia (FTD) is currently distinguished from AD primarily on the basis of behavioral features because studies of cognition have shown negligible or inconsistent differences. However, the poor discriminability of cognitive measures may relate to reliance on imprecise clinically diagnosed groups. Therefore, a retrospective examination of neuropsychological test performance in autopsy-confirmed patients is warranted. OBJECTIVE: To compare the pattern of cognitive deficits exhibited by patients with autopsy-confirmed FTD and AD. METHODS: The profiles of cognitive deficits exhibited by patients with neuropathologic diagnosis of FTD (n = 14) or AD (n = 28) were compared. The Mattis Dementia Rating Scale (MDRS), letter and category fluency tests, Wechsler Intelligence Scale for Children-Revised block design test, Boston naming test, and clock drawing test were administered. RESULTS: Multivariate analysis of covariance controlling for age, education, and level of dementia revealed that patients with FTD performed significantly worse than patients with AD on letter and category fluency tests but significantly better on the MDRS memory subscale, block design test, and clock drawing test. A logistic regression model, validated in an independent clinical sample, used letter fluency, MDRS memory, and block design scores to correctly classify 91% of AD patients and 77% of FTD patients. CONCLUSIONS: A double dissociation in the pattern of cognitive deficits exhibited by FTD and AD patients was demonstrated. The FTD patients were more impaired than AD patients on word generation tasks (i.e., verbal fluency) that are sensitive to frontal lobe dysfunction but less impaired on tests of memory and visuospatial abilities sensitive to dysfunction of medial temporal and parietal association cortices.     

Usefulness of verbal selective reminding in distinguishing frontal lobe memory disorders in epilepsy

Frontal lobe memory disorders are distinguished from hippocampal memory disorders by poor organization of encoding and retrieval, among other things. Because the verbal Selective Reminding Test (SRT) has a metamemory ("remembering-to-remember") component, it may be useful in distinguishing frontal from temporal lobe memory disorders in patients with intractable epilepsy. Thirty-four patients with frontal lobe epilepsy (FLE) and 34 with temporal lobe epilepsy (TLE) underwent a comprehensive neuropsychological evaluation that included multiple memory and executive function tests. Patients with FLE performed significantly worse than those with TLE on SRT measures and Wechsler Memory Scale, Third Edition, Logical Memory (LM II), but not on other verbal and nonverbal memory tests. Furthermore, SRT and LM-II were significantly correlated with executive function measures. These findings have both theoretical and practical implications: (1) the memory impairment observed in frontal lobe disorders may be due, in part, to deficits in organizational strategy, monitoring, and remembering-to-remember, and (2) SRT and LM-II may be useful tests to differentiate frontal from temporal lobe memory disorders.     

Intact verbal and nonverbal short-term memory following damage to the human hippocampus.

Short-term memory was assessed in two groups of amnesic patients. Six patients had confirmed or suspected damage to the hippocampal formation, and six patients had diencephalic damage as a result of alcoholic Korsakoff's syndrome. Verbal short-term memory was evaluated with seven separate administrations of the standard digit span test in order to obtain a precise measure of short-term memory. Nonverbal short-term memory was evaluated with four tests that assessed apprehension, retention, and the ability to manipulate nonverbal material--all within the span of immediate memory. One of these four tests assessed short-term memory for spatial location. Patients with damage to the hippocampal formation had a digit span equivalent to that of control subjects and also performed normally on the four tests of nonverbal short-term memory. The patients with Korsakoff's syndrome had a marginally low digit span and performed poorly on three of the four nonverbal tasks, a finding consistent with the deficits in attention and visuospatial processing previously described for this patient group. These deficits are likely due to the frontal lobe atrophy typically associated with Korsakoff's syndrome, rather than to diencephalic damage. The results support the view that short-term (immediate) memory, including short-term spatial memory, is independent of the hippocampus.     

Dementia and cognitive impairment three months after stroke

To investigate the cognitive capacities of a cohort of ischaemic or haemorrhagic stroke survivors and to identify the clinical determinants of post-stroke cognitive impairment, we evaluated 237 patients admitted to a Stroke Unit (mean age 59; SD=12.7). Three months after stroke, patients were submitted to a neuropsychological evaluation that included the Mini-Mental State Examination (MMSE), a complementary battery to assess specific cognitive domains, the Hamilton Depression Rating Scale (HDRS) and the Blessed Dementia Scale (BDS). Disturbed performance on at least one domain was detected on 131 (55%) patients: 27% had cognitive deficits other than memory, 7% had focal memory deficit, 9% had memory and other cognitive deficits and 6% had dementia. Dementia was associated with female gender (P=0.01), older age (P=0.01) and lower education level (P=0.04). Patients with memory deficits were older (P=0.01) with lower educational level (P=0.08) and more left sided lesions (P=0.02) than patients without memory deficits. In this middle aged stroke survivors cognitive impairment was common 3 months after stroke, while dementia was infrequent.     

A comparison of the information processing deficits of patients with Huntington's chorea and Korsakoff's syndrome.

Patients with Huntington's Chorea and alcholic Korsakoff's disease were compared on six tests of short-term memory (STM) and of encoding capacity. While the alcoholic Korsakoff patients demonstrated STM disorders related to an increase sensitivity to proactive interference (PI) and to failures in semantic encoding, the Chorea patients had a different pattern of deficits. The Chorea patients, like the Korsakoffs, had STM deficits, but their memory performance did not improve with reductions in PI, and they had different types of encoding deficits than did the Korsakoff patients. These results demonstrate that information processing tasks can be used to empirically differentiate amnesic patients with normal I.Q.'s from patients with dementia-related memory impairments.     

The neuropsychological features of mitochondrial myopathies and encephalomyopathies.

Detailed testing of higher cerebral function was performed in 36 patients with mitochondrial myopathies and encephalomyopathies. Fourteen of these patients were thought to be cognitively impaired on clinical grounds. The assessments included tests of general intellectual ability and focal tests of memory, language, and perception. Twenty-one (58%) of the 36 patients who were tested had evidence of general intellectual deterioration, with focal cognitive deficits of variable degree. Of the remaining 15 patients in whom there was no evidence of general intellectual decline, five displayed focal cognitive deficits. In only 10 patients was there evidence of cerebral dysfunction. The range and extent of cognitive deficits in mitochondrial myopathies are greater than predicted by their clinical presentations.     

Neuropsychological findings in toxicometabolic confusional states

Patients with acute confusional states display impaired attention and memory with difficulty following complex verbal commands. In addition to these deficits, we have observed a selective impairment in spatial thinking similar to that present following right-hemisphere lesions. Consequently, we compared patients with acute confusional states (CS) to patients with focal right-hemisphere disease (RHD) and controls on a standard neuropsychological battery. Although impaired relative to controls, both CS and RHD groups did not differ from each other on those tests typically associated with right-hemisphere lesions. These included performance IQ, constructional praxis, spatial judgment, and cancellation tasks. In light of these findings, the neurological correlates of selective deficits in spatial processes include not only unilateral right-hemisphere lesions, but also diffuse disorders such as CS. Thus, there is the potential to misinterpret the neuropsychological test results of patients with diffuse cerebral disorders as indicating focal abnormalities when none exist.     

Neuropsychological impairment in Wilson's disease

To examine the neuropsychological deficits of patients with Wilson's disease (WD), 19 neurologically impaired patients with WD were administered the Wechsler Adult Intelligence Scale (revised), Wechsler Memory Scale, Dementia Rating Scale, Wisconsin Card Sorting Test, Boston Naming Test, Trail Making Test, and Animal Naming Test. Their test scores were compared with those of 12 neurologically asymptomatic patients with WD and 15 normal controls. The neurologically impaired patients scored lower than did the control group on the Performance IQ, Full-Scale IQ, Dementia Rating Scale, and Trail Making Test, and they scored lower on the Wechsler Memory Scale than did both the asymptomatic and control groups. The major areas of deficit for the neurologically impaired WD group were in motor and memory functioning. Computed tomographic and neurologic examinations of the neurologically impaired patients with WD generally reflected abnormalities of the basal ganglia.     

Mnestic performance profile of a bilateral diencephalic infarct patient with preserved intelligence and severe amnesic disturbances

Abstract

The case of a patient with above-average intelligence and educational background, high motivation, and an approximate IQ-MQ difference of 40 points is documented. The patient has been examined repeatedly for nearly a decade. Extensive neuroradiological material of his focal bilateral brain damage in the dorsal diencephalon is available. A widespread range of cognitive tests was used to investigate his actual performance on all relevant aspects of intelligence, attention, subjective memory, immediate retention, learning, skill and problem solving abilities, concept formation, cognitive flexibility, priming, constructional ability, retrograde memory, and long-term retention. The total of more than 50 tests included German-language forms of the revised Wechsler Memory Scale and of the Rivermead Behavioural Memory Test. The patient's short-term memory and attention were, in spite of his advanced years, average or well above average. He gave a number of examples of still intact skills and implicit memory abilities, though there was no uniformity in his performance on implicit memory tests (e.g., with respect to stored vs. new implicit information). He had no awareness of his severe anterograde and retrograde amnesia, documented over a large range of verbal and figural tests. Taken together, the results from our patient confirm the principal dichotomy between declarative and nondeclarative mnestic functions, but give evidence for some restrictions as well. They furthermore demonstrate that focal diencephalic damage may result in profound anterograde and selective retrograde amnesia, especially with respect to data-based material, and that disconnecting portions of the medial and basolateral limbic circuits has devastating consequences on memory.     

Comparative Analysis of Cognitive Function in Schizophrenia with and without Obsessive Compulsive Disorder

Objective

We investigated the neurocognitive deficits in schizophrenic patients with and without obsessive-compulsive disorder (OCD).

Methods

We grouped 27 patients as either obsessive-compulsive or non-obsessive-compulsive based on the presence of OCD. The two groups completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Positive and Negative Symptom Scale (PANSS), and Hamilton Depression Scale. The intelligence quotient (IQ) was tested using the Korean Wechsler Adult Intelligence Scale. The memory quotient (MQ) was tested using the Korean-Auditory Verbal Learning and Korean-Complex Figure Test. The executive intelligence quotient (EIQ) was determined using the Kims executive intelligence test (EXIT).

Results

Ten of the 27 patients had OCD. The compulsion score of Y-BOCS was positively correlated with positive symptoms, negative symptoms, and the total scores of PANSS. The OCD-schizophrenia patients had higher IQs. No difference was found in MQ. Although the EIQ did not differ between the two groups, the OCD-schizophrenia patients performed better at the Stroop-interference and verbal fluency tests, which was highly dependent on executive function.

Conclusion

Our findings suggest that OCD may have a protective effect on some cognitive function, at least in relatively early stage of illness. Moreover, based on clinical, neurocognitive features, schizophrenia with OCD could be considered as a distinct subtype of schizophrenia.     

Memory tests in first-degree adult relatives of schizophrenic patients: a meta-analysis

BACKGROUND: Memory deficits have been clearly demonstrated in schizophrenic patients. However, studies of memory performances in their relatives compared to normal controls provide conflicting results. A meta-analysis was carried out to synthesize all the published data. Unlike previous meta-analyses, which were based on composite scores, we analyzed each memory test separately. This prevents theoretically questionable choices in grouping variables, leads to results with clearer implications for applied research (e.g. the best choice of a test according to its sensitivity) and is more productive in suggesting explanatory hypotheses. METHOD: We initially selected 77 potentially relevant articles, but only 19 met our inclusion criteria. These articles provided data on eight different tasks, from five different memory tests: four tests from the Wechsler Memory Scale (WMS) and the California Verbal Learning Test (CVLT). For each task, we assessed data homogeneity, identified the outliers if any and then estimated effect sizes and tested publication bias using funnel plots. RESULTS: Adult relatives of schizophrenic patients were significantly impaired on most, but not all, tasks. The largest deficits were observed for the verbal paired associates test, the logical stories the digit span forward test and the digit span backward test. We found no significant differences in tasks of delayed recall, when deficits in immediate conditions (reflecting encoding) were taken into account. CONCLUSIONS: Adult relatives of schizophrenic patients have wide but not severe memory impairments. The size of estimated effects suggests that encoding processes are impaired, whereas storage and retrieval processes are relatively unaffected.