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PubMed1997

Patterns of motor impairement in normal aging, mild cognitive decline, and early Alzheimer's disease.

In order to determine the relationship between cognitive dysfunction and motor behavior in older adults, 41 cognitively normal elderly (NL), 25 cases exhibiting mild cognitive impairment (MI), and 25 patients with mild Alzheimer's disease (AD) were examined using a broad array to motor/psychomotor and cognitive tests. Relative to the NL group, MI individuals (at risk for future decline to AD) performed worse on tasks involving fine and complex motor function (e.g., tracking and manual dexterity). AD patients also exhibited motor dysfunction on tasks assessing relatively more rudimentary motor control. Motor tasks were able to distinguish NL vs MI and NL vs mild AD individuals as effectively as cognitive tests of memory and language. These results indicate that motor impairment is an important aspect of cognitive decline in older adults. Motor/psychomotor assessments may be comparably sensitive to traditional tests of cognitive function in identifying persons affected by the earliest stages of AD pathology.

Age Factors↗

PubMed2006

Motor and cognitive improvement by deep brain stimulation in a transgenic rat model of Huntington's disease.

Altered activity of the globus pallidus externus (GPe) is responsible for at least part of the cognitive and motor symptoms of Huntington's disease (HD). In this study, we tested the hypothesis that bilateral globus pallidus (GP; equivalent of GPe in primates) deep brain stimulation (DBS) improves cognitive and motor symptoms in the first transgenic rat model of HD (tgHD rats). GP DBS with clinically relevant stimulation parameters resulted in a significant improvement of cognitive dysfunction and reduced the number of choreiform movements. This data indicate that GPe DBS can be used to treat cognitive and motor dysfunction in HD.

Animals↗

PubMed2003

Profiles of neuropsychologic function in schizophrenia.

In this article, the author reviews basic neuropsychologic issues in the study of schizophrenia. The first issue is whether cognitive dysfunction reflects a degenerative process or is a core feature of the disorder. Evidence demonstrating that cognitive difficulties are present at illness onset and are not caused by medication, illness progression, or other nonspecific factors is reviewed. The second question is less easily answered and deals with whether cognitive difficulties represent generalized dysfunction or differential deficits in specific neurocognitive domains. One difficulty in answering this question is the heterogeneous nature of the disorder. Clinical and cognitive subtyping approaches to reducing heterogeneity are discussed, with the conclusion that cognitive approaches hold the most promise for understanding subtype differences in neurobiologic substrates. Finally, the relation of cognitive ability to functional outcome is described, and it is explained why there is a resurgent interest in remediation efforts. The article closes with suggestions for future directions.

Cognition Disorders↗

PubMed2005

The executive interview as a screening test for executive dysfunction in patients with mild dementia.

OBJECTIVES: To validate the Executive Interview (EXIT25) as a screening instrument for executive cognitive dysfunction in patients with mild dementia. DESIGN: Validation using group comparison and correlation studies. SETTING: The Copenhagen University Hospital Memory Clinic, a multidisciplinary outpatient clinic based in a neurological setting. PARTICIPANTS: Thirty-three patients with mild dementia (MMSE score > or =20) and 30 healthy controls. MEASUREMENTS: The EXIT25, a 25-item screening instrument for executive dysfunction, was administered to all participants. Global cognitive function was measured using the MMSE. Patients were evaluated using traditional neuropsychological tests for executive dysfunction (Wisconsin Card Sorting Test, Trail Making Part B, Stroop Test, verbal fluency, design fluency, and verbal abstraction). Changes in behavior and functional impairment in activities of daily living were assessed using the Frontal Behavioral Inventory (FBI) and the Disability Assessment for Dementia Scale. RESULTS: EXIT25 scores were significantly higher in patients than in the healthy controls; MMSE scores could not account for the differences. Thirteen of the 25 items separated the two groups. EXIT25 was found to correlate significantly with the Stroop Test, the verbal fluency tests, and the FBI. CONCLUSION: The EXIT25 is able to capture executive cognitive deficits not primarily related to the general level of intellectual reduction in patients with mild dementia. In clinical practice, the EXIT25 might be a valuable supplement to the MMSE.

Aged↗

PubMed1995

General cognitive ability following unilateral and bilateral fetal ventral mesencephalic tissue transplantation for treatment of Parkinson's disease.

OBJECTIVE: To contrast the neuropsychological profiles of Parkinsonian patients, before and after fetal ventral mesencephalic tissue transplantation. DESIGN: Case series of personally examined patients. SETTING: Patients were evaluated by neurologists, neurosurgeons, and neuropsychologists as outpatients at a university hospital. PATIENTS: Fetal mesencephalic tissue was implanted in the right caudate nucleus of three patients and both nuclei of one patient. These patients were evaluated prior to surgery and at 12, 24, and 26 months postoperatively. RESULTS: Factor analysis of the test battery identified four statistically orthogonal test clusters. No statistically significant changes were identified postoperatively for clusters assessing verbal cognitive ability, nonverbal cognitive ability, and information-processing speed. An improvement of verbal memory cluster index was observed 12 months after surgery, and the improvement reached the level of statistical significance at 24 months after surgery. However, the verbal memory of all patients declined between 24 and 36 months after surgery. CONCLUSIONS: Fetal tissue transplantation to one or both caudate nuclei did not permanently arrest cognitive dysfunction. Although there is some evidence of improved cognitive ability after transplantation, it is improbable that normal cognitive function can be restored by this procedure because the impairments of cognitive ability associated with Parkinson's disease do not appear to originate solely from dopamine deficiency.

Adult↗

PubMedDate not supplied

Methylphenidate treatment of patients with head and neck cancer.

Five organically impaired and depressed head and neck cancer patients had a marked therapeutic response to methylphenidate (MPD). There was a rapid remission of depressive and cognitive dysfunctions without adverse side effects. The relationship of cognitive, behavioral, and affective symptoms to brain function is discussed. To rule out treatable cognitive and affective disorders, neurobehavioral assessment of the depressed head and neck cancer patient is stressed, and diagnostic and treatment guidelines are given. The results suggest that further evaluation is warranted of the use of MPD in treating seriously ill cancer patients who have either compromised brain function or depression.

Aged↗

PubMed2006

The impact of diabetes mellitus on cognitive decline in the oldest of the old: a prospective population-based study.

AIMS/HYPOTHESIS: Diabetes mellitus is a risk factor for the development of cognitive impairment and dementia in the general population up to 75 years of age. As part of the Leiden 85-plus Study we studied the effects of diabetes on cognition in the oldest old. SUBJECTS AND METHODS: The Leiden 85-plus Study is a prospective population-based study of 599 persons from age 85 onward. Cognitive function was assessed each year from ages 85 to 90 by means of four neuropsychological tests. The presence of diabetes and vascular disease was recorded at baseline, HbA(1c) was assessed by means of a blood sample at ages 85 and 90. The cross-sectional and prospective associations between diabetes and cognitive function were analysed with linear mixed models, adjusted for sex and level of education. RESULTS: At age 85, diabetes was associated with a lower level of cognitive functioning on the Letter Digit Coding test and the Stroop Test. Diabetes was not associated with accelerated cognitive decline during follow-up. Within the group of diabetic patients, macrovascular disease was the most important determinant of cognitive dysfunction. CONCLUSIONS/INTERPRETATION: The association between diabetes and accelerated cognitive decline, which has been documented previously in patients up to 75 years of age, may be less evident after age 85. This suggests that the damage occurs in previous years and that therapies aimed at preventing cognitive decline and dementia should focus on the younger old.

Aged, 80 and over↗

PubMed1999

Dopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys.

D4 dopamine receptors (DRs) are enriched in the primate prefrontal cortex, a brain region implicated in cognitive processes, and mesoprefrontal dopaminergic systems appear to be involved in modulating some cognitive functions of the prefrontal cortex. Despite anatomical localization of D4 DRs within the frontal cortex, the role of these receptors, specifically, in the regulation of cognition or behavior in primates is unknown. In these studies, we sought to learn whether specific antagonism of D4 DRs would affect performance of a task dependent on the frontostriatal system. The effects of NGD94-1 (2-phenyl-4(5)-[4-(2-pyrimidinyl)-piperazin-1-yl)-methyl]-imidazol e dimaleate), a potent and selective D4 DR antagonist and haloperidol, a non-specific D2-like DR antagonist, on the performance of an object retrieval/detour task by monkeys were examined. The effects of these antagonists on the object retrieval task were evaluated in normal control monkeys and in subjects repeatedly exposed to phencyclidine (PCP), to induce frontal cortical dopaminergic and cognitive dysfunction. NGD94-1 (1-5 mg/kg) reversed the cognitive deficits of PCP pre-treated monkeys, whereas haloperidol (25 microg/kg) exacerbated PCP-induced performance impairments. A low dose of NGD94-1 failed to affect performance of control subjects, while both haloperidol and a high dose of NGD94-1 impaired control performance. These data show, for the first time, that D4 DRs modulate the cognitive functions of the frontostriatal system.

Animals↗

PubMed2003

Anterior cingulotomy for refractory obsessive-compulsive disorder.

OBJECTIVE: This study was designed to prospectively investigate the efficacy and cognitive adverse effects of stereotactic bilateral anterior cingulotomy as a treatment for refractory obsessive-compulsive (OCD) patients for 12 months. METHOD: Patients were eligible if they had severe OCD and rigorous treatments had been unsuccessful. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Clinical Global Impression (CGI) and neuropsychological tests were used to assess the efficacy and cognitive changes of cingulotomy before and 12 months after operation. RESULTS: The mean improvement rate of the Y-BOCS scores achieved from baseline was 36.0%. Out of 14 patients six met responder criteria; 35% or higher improvement rate on Y-BOCS and CGI improvement of very much or much better at 12-month follow-up. There was no significant cognitive dysfunction after cingulotomy. CONCLUSION: Anterior cingulotomy shows few cognitive adverse effects, with about half of the OCD patients demonstrating significant symptomatic improvement.

Adult↗

PubMed1990

Negative and positive cognition in depressed and nondepressed chronic-pain patients.

Several studies have suggested that depressed pain patients evidence more cognitive distortion than nondepressed pain patients and healthy controls. Although these studies have generally supported notions relating cognitive distortion to depressive functioning, other aspects of dysfunctional cognition have not been assessed in the chronic-pain population. The present study examined negative and positive automatic thoughts and attributional style in depressed pain patients, nondepressed pain patients, and healthy controls. Depressed chronic-pain patients were found to exhibit significantly more negative automatic thoughts than nondepressed pain patients and healthy controls. Conversely, nondepressed chronic-pain patients reported significantly more positive automatic thoughts than did depressed patients and healthy controls. No significant differences were found for attributional style. These results suggest that different cognitive-behavioral interventions might be considered for depressed compared to nondepressed chronic-pain patients.

Back Pain↗

PubMedDate not supplied

The Short Portable Mental Status Questionnaire: assessing cognitive ability in nursing home residents.

BACKGROUND: The Short Portable Mental Status Questionnaire (SPMSQ) and other brief tests of cognitive functioning have been widely used to screen for cognitive dysfunction; however, they are rarely used to assess cognitive ability. OBJECTIVES: To discern whether the SPMSO might adequately substitute for longer assessments in the prediction of memory performance in older adults. METHOD: The SPMSQ and grocery list and prose recall tests were administered to 67 cognitively intact nursing home residents (mean age = 75 years). Demographic characteristics and self-rated health were recorded. RESULTS: The number of items missed on the SPMSQ predicted up to 32% of the variance in more extensive list and prose recall measures, even with demented patients excluded. The SPMSQ retained a strong predictive relationship to memory after age variance was removed, accounting for 11-16% of the variance. CONCLUSIONS: The SPMSQ may be useful as a general measure of cognitive abilities in nursing home residents.

Aged↗

PubMed2006

Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging With HIV cohort.

OBJECTIVE: To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk. DESIGN: Cross-sectional analysis within the Hawaii Aging With HIV Cohort. METHODS: We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses. RESULTS: Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores. CONCLUSIONS: IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.

AIDS Dementia Complex↗

PubMedDate not supplied

The effect of galantamine added to clozapine on cognition of five patients with schizophrenia.

Although clozapine may be beneficial for the treatment of cognitive dysfunction in schizophrenia, it may also impair some cognitive skills as a result of its anticholinergic activity. In this case series, the impact of galantamine administration on 5 patients with schizophrenia who had been treated with clozapine are reported. Neuropsychological assessment was administered before and after 8 weeks of 16 mg/d galantamine treatment. In this case series, galantamine was well tolerated by all of the patients. Three of the patients were much improved in sustained attention tasks. Most of the patients were also improved in psychomotor speed and selective attention tasks. Two patients with low pretreatment memory scores seemed to also be improved. Our results suggest that the possible role of galantamine as a cognitive enhancer in schizophrenia should be investigated in controlled trials.

Adult↗

PubMed2006

Type 2 diabetes, cognitive function and dementia: vascular and metabolic determinants.

Type 2 diabetes is a common metabolic disease with a rising global prevalence. It is associated with slowly progressive end-organ damage in the eyes and kidneys, but also in the brain. The latter complication is often referred to as "diabetic encephalopathy" and is characterized by mild to moderate impairments in cognitive functioning. It is also associated with an increased risk of dementia. To date, its pathogenetic mechanisms are largely unclear. Cognitive impairments in patients with type 2 diabetes have been associated both with vascular risk factors, such as hypertension and dyslipidemia, and with diabetes-related factors, such as glycemic control, duration of the disease and treatment modality. Studies that address these associations generally focus on statistical (in)dependence of certain risk factors in the association between type 2 diabetes and cognitive decline rather than the causality of the association, which, from a mechanistic point of view, is more relevant. In this review we describe the association between type 2 diabetes and cognitive dysfunction and dementia. Furthermore, potential determinants of impaired cognition in type 2 diabetes are addressed both from the perspective of statistical associations and from a mechanistic point of view.

Brain↗

PubMed1987

Comparison of two cognitive rating scales in medically ill patients.

Patients with acute, complex behavioral syndromes combined with impaired comprehension and communication are difficult diagnostic challenges. Using a structured mental status interview can significantly reduce the chance of overlooking the presence of cognitive dysfunction. The authors tested the applicability of the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-COG) as a screening instrument on a psychiatric consultation service. The ADAS-COG compared favorably with the Mini-Mental State Exam (MMSE), but appeared to be less influenced by educational level. The advantages and disadvantages of using each of these tests on a psychiatric consultation service are discussed.

Adult↗

PubMed1992

Progressive multifocal leukoencephalopathy in patients with HIV infection: lack of impact of early diagnosis by stereotactic brain biopsy.

Thirteen patients with HIV-related progressive multifocal leukoencephalopathy (PML), representing an institutional incidence of 4.2%, are reported. All cases were diagnosed by image guided stereotactic brain biopsy shortly after their presentation for neurologic complaints. All patients were males; risk factors included homosexual or bisexual activity or intravenous drug use. At the time of presentation with PML, the mean T4 count was 85 (range 9-240 cells/mm3). The most common neurologic symptoms were cognitive dysfunction and aphasia, whereas gait abnormalities and disordered cognition were the most common neurologic signs. Cerebrospinal fluid analysis was helpful only to rule out other causes of CNS disease. Magnetic resonance imaging, more sensitive than computed tomography (CT) scanning, typically revealed multiple areas of increased intensity on T2 weighted images although unifocal disease was seen in 23% of patients. Despite early stereotactic biopsy and aggressive symptomatic therapy, survival of these patients was poor with a mean of 2.6 months after the onset of neurological symptoms and 2.0 months after biopsy.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Early-stage visual processing deficits in schizophrenia.

PURPOSE OF REVIEW: While cognitive dysfunction including memory and attentional deficits are well known in schizophrenia, recent work has also shown basic sensory processing deficits. Deficits are particularly prominent in the visual system and may be related to cognitive deficits and outcome. This article reviews studies of early-stage visual processing in schizophrenia published during the past year. These studies reflect the growing interest and importance of sensory processing deficits in schizophrenia. RECENT FINDINGS: The visual system is divided into magnocellular and parvocellular pathways which project to dorsal and ventral visual areas. Recent electrophysiological and behavioral investigations have found preferential magnocellular/dorsal stream dysfunction, with some deficits in parvocellular function as well. These early-stage deficits appear to be related to higher level cognitive, social, and community function. Structural studies of occipital cortex and particularly optic radiations provide anatomical support for early visual processing dysfunction. SUMMARY: These findings highlight the importance of sensory processing deficits, in addition to higher cognitive dysfunction, for understanding the pathophysiology of schizophrenia. Understanding the nature of sensory processing deficits may provide insight into mechanisms of pathology in schizophrenia, such as N-methyl-D-aspartate dysfunction or impaired signal amplification, and could lead to treatment strategies including sensory processing rehabilitation that may improve outcome.

Journal Article↗

PubMed1999

Prefrontal dysfunction following unilateral posteroventral pallidotomy in Parkinson's disease.

OBJECT: Pre- and postoperative cognitive function was evaluated in 25 patients with Parkinson's disease (PD) who underwent unilateral posteroventral pallidotomy (PVP) to clarify the effects of this operation on cognitive function. METHODS: Cognitive function was assessed before surgery and 1 month and 3 months afterward by using a battery of neuropsychological tests consisting of orientation, digit span (forward and backward), digit learning, 5-minute memory of five words, similarities, serial sevens, animal name listing, and the kana pick-out test, as well as the Japanese version of the Mini-Mental State. Preoperative evaluation revealed that patients experienced difficulties in performing the neuropsychological tasks of reasoning and abstraction, working memory of numerals, word fluency, and concept formation compared with 36 healthy volunteers (p < 0.05). A simple regression analysis showed strong relationships in a negative fashion between preoperative (r = 0.81, p = 0.002) and 1-month (r = 0.79, p = 0.0059) and 3-month (r = 0.85, p = 0.0016) postoperative gross-total scores and Hoehn and Yahr staging. Preoperative and postoperative scores at 1 month and 3 months were analyzed by analysis of variance, but only the Fisher's post hoc test revealed the source of difference. All tasks except orientation (p = 0.0292) were unchanged in the 10 patients who underwent surgery on the right side. The scores for this task at 1 month postsurgery were significantly lower (p = 0.0203) but improved to preoperative values by 3 months. In the 15 patients who underwent surgery on the left side significant differences among tasks were revealed for serial sevens (p = 0.0471) and animal naming (p = 0.0425). The scores for these tasks were significantly lower at 1 month postoperatively (p = 0.0431 for serial sevens and p = 0.0408 for animal naming), but improved by 3 months after the operation. CONCLUSIONS: The present data revealed that cognitive dysfunction in patients with PD relates to advancement of Hoehn and Yahr stage, but PVP is not associated with significant long-lasting cognitive deficits.

Aged↗