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PubMed1994

Brain disease and molecular analysis in myotonic dystrophy.

Abnormal amplification of a CTG repeat on chromosome 19 is the molecular basis of myotonic dystrophy (DM). Expansion of the repeat has been correlated with severity of several clinical features of the disease. We performed extensive cognitive testing, cerebral magnetic resonance imaging (MRI) and a molecular analysis in 28 cases of DM to determine the relationship between the molecular defect and brain disease. Performance in two or more cognitive tests was pathological in 10 cases. Fourteen patients had subcortical white matter lesions on MRI, 14 had cerebral atrophy. Amplification of the CTG repeat showed a strong correlation with cognitive test deficits when exceeding a length of over 1000 trinucleotides. MRI lesions were associated with impaired psychometric performance, but MRI and molecular findings were only weakly related. Disease duration influenced the appearance and amount of white matter lesions on MRI. Quantification of CTG repeat size may allow an early estimate on the probability of brain involvement in DM; cognitive dysfunction is associated with white matter lesions and cerebral atrophy later on in the course.

Adult↗

PubMedDate not supplied

Selected cognitive losses after stroke. Frequency, recovery and prognostic importance.

Data collected in a population-based study on 976 patients suffering an acute stroke have been analysed to discover the frequency of disturbance of selected cognitive functions, particularly orientation, non-verbal reasoning, and copying. Further analysis investigated how these deficits related to other impairments, their prognostic importance, and their recovery. Considering patients assessed within the first week, only 45% were orientated, only 44% could be assessed for IQ and their average score was 94 (SD 16), and only 36% could copy a cross satisfactorily. Seventeen per cent of patients had a reduced level of consciousness preventing assessment, and the other unassessable patients had other impairments such as aphasia preventing assessment. In general failure to pass these tests was associated with evidence of a more severe stroke; the patients had other impairments such as a more severe paralysis. No independent effect of cognitive dysfunction upon recovery could be demonstrated. By 6 months most surviving patients passed all the tests used.

Activities of Daily Living↗

PubMed2006

[Cognitive function in patients with severe carotid stenosis--evaluation of RBANS, WAIS-R and NART before treatment of carotid revascularization--].

PURPOSE: To evaluate the cognitive function in preoperative patients with severe carotid stenosis. PATIENTS AND METHOD: Twenty-five patients with severe carotid stenosis were examined on their cognitive function by RBANS (Japanese version), WAIS-R (Japanese version), and NART (Japanese version) before treatment of carotid revascularization (endarterectomy or stenting). They had full activities of daily living without any hemiparesis, aphasia, agnosia, and apraxia at the time of the examinations. RESULTS: Mean intelligent quotient (IQ) measured by WAIS-R and NART was 104.0 +/- 10.7 and 101.3 +/- 13.4, (ns) respectively. Mean total scale of RBANS was 90.0 +/- 13.4, which was significantly lower than both the results of WAIS-R and NART. A mean value of each RBANS index was 91.3 +/- 11.7 in immediate memory, 102.0 +/- 18.2 in visuospatial/constructional, 93.2 +/- 8.7 in language, 84.6 +/- 14.7 in attention, and 92.1 +/- 14.4 in delayed memory. RBANS index significantly declined in immediate memory, language, attention and delayed memory than visuospatial/constructional. CONCLUSIONS: Qualitative evaluation was available in RBANS, WAIS-R, and NART, which enabled the investigators to make a precise comparison between these methods. WAIS-R and NART showed a comparatively preserved function and were presumed to be useful for the evaluation of the baseline of cognitive function in preoperative patients. RBANS demonstrated a slight decrease in memory and attention in those patients and was expected to be useful to detect the cognitive dysfunction when compared with WAIS-R and NART.

Activities of Daily Living↗

PubMed1989

High plasma levels of cortisol in patients with senile dementia of the Alzheimer's type.

Plasma cortisol levels and other factors including thyroid hormone in patients with Alzheimer's type (n = 10), vascular type (n = 10) or mixed type (n = 10) senile dementia were compared with those in non-demented senile controls (n = 10). Plasma cortisol levels at 8:00 a.m. in Alzheimer's type dementia and mixed type dementia were 17.3 +/- 4.3 micrograms/dl (mean +/- SD) and 15.6 +/- 2.3 micrograms/dl, respectively. These values were significantly higher (p less than 0.005 and p less than 0.01) than those found in the control subjects (12.0 +/- 3.1 micrograms/dl). Plasma cortisol levels in vascular-type dementia (14.4 +/- 6.3 micrograms/dl) did not differ significantly from those in the controls. Plasma ACTH in senile dementia of the Alzheimer's type was lower, but not significant as compared with that in normal controls. In three subgroups of senile dementia and normal controls, plasma cortisol levels inversely correlated significantly with the degree of cognitive function. Plasma levels in TSH-thyroid system and blood pressure did not show any significant change in three types of senile dementia. These data suggest that senile dementia of the Alzheimer's type accompanies relatively and primarily high plasma cortisol levels and this may associate with cognitive dysfunction in Alzheimer's type senile dementia.

Adrenocorticotropic Hormone↗

PubMed2005

Protective effects of FBD--an experimental Chinese traditional medicinal formula on memory dysfunction in mice induced by cerebral ischemia-reperfusion.

With regards to the applications of three Chinese herbs poria, rhizoma atractylodis macrocephalae, and radix angelicae sinensis to vascular dementia (VD), the work was performed to assess the nootropic action and explore neuroprotective mechanisms of three herbs combinations (FBD) on mice injured by cerebral repetitive ischemia-reperfusion (IR). Aqueous extracts from FBD (115-460 mg/kg) administered p.o. significantly improved cognitive function through elongating latency and reducing number of errors in step-through test. Aqueous extracts from FBD inhibited lipid peroxidation (LPO), elevated activity in (Na+)-(K+)-ATPase and (Ca2+)-ATPase, reduced the production of nitric oxide (NO) in cortical tissue after IR, and artificial cerebrospinal fluid (ACSF) containing aqueous extracts from FBD (ACSF-FBD) (0.01-10 mg/L) protected also primary cortical cortex neurons (PCCN) from hypoxic and excitotoxic insult induced by sodium dithionite (1 mM) and monosodium glutamate (MSG) (0.5 mM) in vitro. Multiple anti-IR properties contributed probably FBD to ameliorate cognitive dysfunction shown in this murine model for VD.

Animals↗

PubMed2004

Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk?

BACKGROUND: Apathy has been shown to be an important feature of degenerative, vascular or traumatic brain disorder. Its presence is associated with high depression scores, higher age, low performance on frontal tasks, and more severe deep white matter hyperintensities. In late-life depression, lack of interest or motivation are often more prominent than depressed mood, especially in the late-onset type. It was hypothesized that in a heterogeneous sample of elderly depressed patients, apathy is associated with late-onset type of depression, cognitive dysfunction or vascular risk factors. METHOD: The Apathy Evaluation Scale (AES) was administered to twenty-nine elderly (> or = 60 years) inpatients with a DSM-IV major depression or dysthymic disorder. The severity of the depression was measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The presence of vascular risk factors was traced in the patient's medical records. RESULTS: Apathy was found in 86% of the patients. The AES-score was correlated with the negative symptom score, but not with total MADRS or MMSE-score. No difference in AES-score between early-onset depressed (n = 16) and late-onset depressed (n = 13) patients was found, and between patients with or without vascular risk. CONCLUSION: Apathy is a main feature of moderate to severe depressive illness in elderly patients and related to the negative symptoms of the disorder. Further studies should include less severely depressed patients and investigate the relation between depression severity and apathy.

Age of Onset↗

PubMedDate not supplied

[Neuropsychological evaluation in a case of multiple sclerosis].

INTRODUCTION: The neuropsychological assessment of patients with multiple sclerosis (MS) may be diagnostically useful to provide a patient's cognitive profile, to observe the spread of the deficit and to identify the peculiar areas that are more or less affected, in order to plan a long-term management and treatment. CLINICAL CASE: In this article, we present a case of cognitive dysfunction associated with a progressive MS in a 54 years woman, which was diagnosed six years ago. The magnetic resonance imaging showed demyelinating lesions at the periventricular region, with left predominance, and in the protuberance with signs of cortico-subcortical atrophy. We performed neuropsychological assessment of the main cognitive areas: orientation, attention, information processing, memory, general intelligence functioning, language, arithmetic, visual-spatial functioning, motor, executive functioning and personality. CONCLUSIONS: The results obtained point out serious alterations in the information speed processing, long term memory, motor, executive functioning and personality. This results go in a concordant way with the results reported in the consulted bibliography. Likewise, it is commented the resemblance of the cognitive deficit related to a pattern of subcortical dementia.

Affect↗

PubMed1989

Lateralized cerebral dysfunction in schizophrenia and depression: gender and medication effects.

The neuropsychological functioning of 52 schizophrenic and 39 major depressive patients was examined using the four Luria-Nebraska Neuropsychological Battery lateralization scales, with the effects of gender and medication status examined alone and in interaction with diagnosis and laterality variables. Comparisons between the diagnostic groups revealed that gender influences some aspects of neuropsychological performance, particularly those involving bilateral complex cognitive-perceptual rather than sensorimotor skills. This effect was more distinct for depressives than schizophrenics when cerebral lateralization differences were present. There was no significant left hemisphere disadvantage for schizophrenics which was gender-related. Medication status revealed no appreciable effects for depressives, although both male and female schizophrenics receiving neuroleptics showed a greater degree of complex perceptual-cognitive dysfunction compared to unmedicated schizophrenics. Level of cerebral impairment was equivalent for the right and left hemispheres for both groups. Consequently, these data are not consistent with other findings demonstrating differential hemispheric disadvantages between schizophrenia and depression.

Journal Article↗

PubMed1996

Repeat neurobehavioral study of borderline personality disorder.

Previous research has tentatively identified a large subgroup of patients with borderline personality disorder (BPD) with histories of developmental or acquired brain insults. Similarly, these studies have demonstrated a possible biological correlation between the severity of BPD and the number of previous brain insults. The possibility of frontal system cognitive dysfunction in BPD has been raised. This single-blind, case-control study of BPD showed that 13 of 24 subjects with BPD had suffered a brain insult. Correlations between neurodevelopmental/acquired brain injury score and the diagnostic interview for borderline (DIB) score (r = 0.47), and between frontal system cognitive functioning and DIB score (r = -0.37) were seen. Neurocognitive testing and comparison with a cohort of subjects with traumatic brain injury (TBI) showed a pattern of similar cognitive functioning between the 2 groups, with the only differences on individual tests being in the direction of worse functioning in the group with BPD on 2 tasks. These results support the hypotheses described above. The main limitation reflects the low numbers of subjects.

Adult↗

PubMed1998

Reversible combined cognitive impairment and severe polyneuropathy resulting from primary hyperparathyroidism.

Central and peripheral nervous systems may be involved in primary hyperparathyroidism (PHP). The efficacy of parathyroidectomy in reversing neurological symptoms is still a matter of controversy. We describe the case of a 71-year-old white male with a 10-year history of PHP who developed progressive cognitive dysfunction and severe sensorimotor axonal polyneuropathy. Successful parathyroidectomy reversed with a different temporal course both the central and peripheral nervous system involvements.

Aged↗

PubMed2005

Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex.

BACKGROUND: Amphetamine (AMPH) sensitization in monkeys produces long-lasting behavioral changes that model positive (hallucinatory-like behaviors) and negative (psychomotor depression) symptoms of schizophrenia. The extent to which this model produces the core deficit in schizophrenia--working memory impairment--is unknown. METHODS: Two groups of rhesus monkeys were sensitized to AMPH over 6 weeks. In one group, acquisition of cognitive tasks (delayed response, visual discrimination, delayed nonmatch-to-sample) was examined beginning 6+ months postsensitization. The second group was pretrained to stability on delayed response before sensitization. Regional postmortem concentrations of dopamine and its metabolites were examined in tissue from age-matched AMPH-naive and AMPH-sensitized monkeys using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). RESULTS: The AMPH-sensitized monkeys were profoundly impaired in their ability to acquire cognitive tasks compared with AMPH-naïve monkeys. Pretrained monkeys showed impaired delayed response performance for several months following sensitization. Analysis by HPLC revealed that AMPH sensitization significantly reduced dopamine turnover in prefrontal cortex and striatum. CONCLUSIONS: Impairments in the acquisition and performance of spatial delayed response in association with reduced dopamine turnover in prefrontal cortex following AMPH sensitization provide further support for the relevance of this model to both the etiology and the treatment of cognitive dysfunction in schizophrenia.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2026

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20 mg/day over 6 weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n = 31; placebo, n = 32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P < 0.001), but improvement was greater with memantine for global cognition at week 6 (MD = 9.32; 95% CI, 4.84-13.81; P < 0.001) and week 18 (MD = 12.69; 95% CI, 8.67-16.71; P < 0.001). FAB total scores favored memantine at week 18 (MD = 2.68; 95% CI, 1.76-3.61; P < 0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans↗

PubMed1997

Event-related potentials (P300) and EEG activity in childhood partial epilepsy.

To clarify the relationship between the cognitive function and EEG activity, auditory event-related potentials (P300) were examined in 72 patients with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). For this study, patients undergoing carbamazepine monotherapy with a dose of less than 16 mg/kg/day were selected to rule out the effects of anti-epileptic drugs. The results were as follows: (1) The P300 latency tended to be prolonged in association with the EEG slowing in both epileptic groups. (2) There was no clear relationship between the frequency of paroxysmal discharges and the P300 latency. (3) The P300 latency was slightly prolonged in the patients with temporal foci compared with that in ones with extra-temporal foci. (4) There was no significant relationship between the generalization of focal paroxysmal discharges and the P300 latency. These results suggested that the influence of EEG abnormalities (particularly paroxysmal discharges) on the P300 latency is relatively little, and the cognitive dysfunction in partial epilepsies mainly originates from other factors such as the epileptogenic lesion itself.

Adolescent↗

PubMed1989

Cognitive therapy of panic disorder. A nonpharmacological alternative.

A naturalistic study with no predetermined duration of treatment was undertaken in order to examine the effectiveness of cognitive therapy in the treatment of panic disorder. Seventeen patients diagnosed as having panic disorder according to the Structured Clinical Interview for DSM-III Personality Disorders received a mean of 18 individual cognitive therapy sessions. Patients with personality disorder or depression required a longer duration of treatment to become symptom-free. As measured by a self-report weekly panic log, the mean number of panic attacks was reduced significantly to zero at the end of treatment. There was a concomitant reduction in self-report measures of depression and anxiety. Further, there was a significant reduction on a measure of cognitive dysfunction during panic attacks. Treatment results were maintained at 12-month follow-up.

Adolescent↗

PubMed2005

Apathy correlates with cognitive function but not CD4 status in patients with human immunodeficiency virus.

Apathy is a prominent neuropsychiatric symptom associated with human immunodeficiency virus (HIV). The increased frequency of apathy in this population may reflect the direct involvement of the virus on the central nervous system (CNS), but the severity of apathy has not been shown to consistently relate to markers of disease activity or other neuropsychiatric complications of the virus. We examined the relationship between ratings of apathy and performance on measures of cognitive function and immune system status in a sample of HIV-infected patients. Apathy was significantly elevated among HIV-infected individuals compared to healthy comparison subjects. Apathy was significantly related to performance on measures of learning efficiency and a measure of cognitive flexibility. Ratings of apathy did not relate to CD4 cell count, but they were associated with disease duration. In addition, ratings of depression were independent of ratings of apathy. These findings suggest that apathy does not co-vary with a proxy measure of active disease status, but apathy does relate to several measures of cognitive dysfunction in patients with HIV. As such, the increased prevalence of apathy among HIV-infected adults may reflect HIV-associated neurologic dysfunction.

Adult↗

PubMedDate not supplied

[Clinical and neuropsychological correlates of proton magnetic resonance spectroscopy detected metabolites in brains of first-episode and schizophrenic patients].

OBJECTIVE: This study examined 1H MRS detected metabolite levels (in left frontal, temporal lobes and thalamus) and clinical and cognitive features of patients with first-episode and chronic schizophrenia. METHOD: We studied 31 first-episode patients (group 1) and 17 chronic patients (group 2) with ICD-10 diagnosis of schizophrenia (and 13 healthy subjects). Patients were also assessed by the means of PANSS, CGI, Calgary scales and WCST, TMT, Stroop tests. RESULTS: We did not observe statistically significant differences in metabolite levels between group 1 and 2. We observed only a trend toward higher Cho level in temporal lobe in group 2 and lower NAA level in group 1. When comparing with the control group we observed a significantly higher Cho level in the frontal lobe (group 1,2) (p < 0.05). We observed a trend toward lower NAA levels in the frontal lobe (group 1,2), and lower NAA level in the temporal lobe (group 1). Patients with chronic schizophrenia performed significantly worse in WCST, TMT and Stroop tests (p < 0.05). CONCLUSION: These results suggest, that abnormalities in metabolite levels in frontal and temporal lobes are present at the onset of disease and don't progress over time. The cognitive dysfunction is more prominent in chronic patients.

Acute Disease↗

PubMed2006

Metabolic brain networks associated with cognitive function in Parkinson's disease.

The motor manifestations of Parkinson's disease (PD) have been linked to an abnormal spatial covariance pattern involving basal ganglia thalamocortical pathways. By contrast, little is known about the functional networks that underlie cognitive dysfunction in this disorder. To identify such patterns, we studied 15 non-demented PD patients using FDG PET and a voxel-based network modeling approach. We detected a significant covariance pattern that correlated (p<0.01) with performance on tests of memory and executive functioning. This PD-related cognitive pattern (PDCP) was characterized by metabolic reductions in frontal and parietal association areas and relative increases in the cerebellar vermis and dentate nuclei. To validate this pattern, we analyzed data from 32 subsequent PD patients of similar age, disease duration and severity. Prospective measurements of PDCP activity predicted memory performance (p<0.005), visuospatial function (p<0.01), and perceptual motor speed (p<0.005) in this validation sample. PDCP scores additionally exhibited an excellent degree of test-retest reliability (intraclass correlation coefficient, ICC=0.89) in patients undergoing repeat FDG PET at an 8-week interval. Unlike the PD-related motor pattern, PDCP expression was not significantly altered by antiparkinsonian treatment with either intravenous levodopa or deep brain stimulation (DBS). These findings substantiate the PDCP as a reproducible imaging marker of cognitive function in PD. Because PDCP expression is not altered by routine antiparkinsonian treatment, this measure of network activity may prove useful in clinical trials targeting the progression of non-motor manifestations of this disorder.

Brain↗

PubMed2003

The effects of cognitive impairment on mortality among hospitalized patients with heart failure.

PURPOSE: Cognitive impairment is a common, potentially reversible condition among older patients with heart failure. Because cerebral metabolic abnormalities have been associated with reduced survival in younger patients with advanced heart failure, we assessed the effect of cognitive impairment on the survival of older patients with heart failure. METHODS: The association between cognitive dysfunction and in-hospital mortality was assessed in 1113 patients (mean [+/- SD] age, 78 +/- 9 years) who had been admitted for heart failure to 81 hospitals throughout Italy. One-year mortality was assessed in 968 patients with heart failure (age, 76 +/- 10 years) participating in the same study. Cognitive impairment was defined as a Hodkinson Abbreviated Mental Test score <7. RESULTS: In-hospital death occurred in 65 (18%) of the 357 participants with cognitive impairment and in 26 (3%) of the 756 patients with normal cognition (P <0.0001). Out-of-hospital mortality was 27% (51/191) among patients with cognitive impairment and 15% (115/777) among other participants (P <0.0001). In multivariate Cox regression models, decreasing levels of cognitive functioning were associated with increasing in-hospital mortality; cognitive impairment was associated with an almost fivefold increase in mortality (relative risk = 4.9; 95% confidence interval: 2.9 to 8.3) after adjusting for several potential confounders. CONCLUSION: Cognitive impairment is an independent prognostic marker in older patients with heart failure. Assessment of cognitive functioning, even by simple screening tests, should be part of the routine assessment of elderly patients with heart failure.

Age Distribution↗