Behavioural abnormalities contribute to functional decline in Huntington's disease

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington's disease are examined. Twenty two patients with Huntington's disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington's disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.     

Cognitive dysfunction in different stages in multiple sclerosis--presentation of 3 cases

Although multiple sclerosis (MS) is a physically disabling disease, many patients also suffer from cognitive dysfunction in all stages of the disease. Recent studies have demonstrated that 45 up to 65% of MS patients are cognitively impaired. The profile of MS-related cognitive dysfunction varies greatly. It includes memory and learning deficits, attention deficits, executive dysfunction and visuo-spatial deficits. Most studies of cognition in MS examined patients in later stages, often including MS patients with marked physical disabilities. Our own studies revealed cognitive dysfunction in MS patients within the early stage of disease as well. In this paper, three patients with MS in different stages and with different MRI-findings will be presented in consideration of cognitive dysfunction in particular.     

Cognition in the early stage of multiple sclerosis

Objective Cognitive dysfunctions may contribute to limitation of everyday activities of patients with multiple sclerosis (MS). Recent studies have demonstrated that 45 to 65% of MS-patients are cognitively impaired. The profile of MS-related cognitive dysfunctions varies greatly. It includes memory and learning deficits, attention deficits, executive dysfunctions and visuo-spatial deficits. Most studies of cognition in MS examined patients in later stages, often including MS-patients with marked physical disabilities. Studies of cognitive dysfunctions in the early stage of the disease are rare. This study specifically aimed at evaluating and characterizing cognitive impairments in the early stage of MS, and determining specific patterns of cognitive dysfunction. Methods 21 MS patients, experiencing their first neurological symptoms not more than two years previously, and 22 healthy controls were compared. A comprehensive neuropsychological test-battery was used to evaluate MS-related cognition. The battery consisted of memory and learning tests, executive functioning tests and a visuo spatial functioning test. A computerized attention test-battery was also included, which assess accuracy and speed of test responses. In addition depression and intellectual capabilities were assessed. Results Compared with healthy controls, MS-patients in the early stage of the disease performed significantly lower on each neuropsychological assessment, except for verbal short-term memory. In particular, MS-patients showed a lengthened reaction time for simple and focused attention (19–38%), impaired non-verbal memory function (RVDLT recognition: 33%) and a planning deficit (24%). Associations between information processing speed and disease course and the employment situation were additionally found. However, patients did not have clinically relevant depression rates on the ADS-L and visuo spatial abilities remain preserved. Conclusion Our findings revealed discrete cognitive dysfunction in MS-patients within the early stage of the disease. Received in revised form: 18 January 2006     

Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years

OBJECTIVE: To reassess, in a cohort of patients with early-onset multiple sclerosis, the long-term evolution of cognitive deficits, their relationship to the disease's clinical progression, and their effects on daily life. DESIGN: Ten years after our baseline assessment, we again compared the cognitive performance of patients and control subjects on a neuropsychological test battery. Clinical and demographic correlates of cognitive impairment and their effects on everyday functioning were determined by multiple linear regression analysis. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: Forty-five inpatients and outpatients with multiple sclerosis and 65 demographically matched healthy controls from the original sample. MAIN OUTCOME MEASURES: Mean scores of both groups on the neuropsychological test battery in initial and 2 follow-up evaluations (about 4 and 10 years, respectively); number of cognitively impaired subjects, defined by the number of subtests failed; regression coefficients measuring the relationship between clinical variables and cognitive outcome and between mental decline and everyday functioning assessed by the Environmental and the Incapacity Status Scales. RESULTS: Previously detected cognitive defects in verbal memory, abstract reasoning, and linguistic processes were confirmed on the third testing, at which time deficits in attention/short-term spatial memory also emerged. Only 20 of 37 patients who were cognitively unimpaired on initial testing remained so by the end of the follow-up, when the proportion of subjects who were cognitively impaired reached 56%. Degree of physical disability, progressive disease course, and increasing age predicted the extent of cognitive decline. Disability level and degree of cognitive impairment were independent predictors of a patient's handicap in the workplace and in social settings. CONCLUSIONS: In the course of a sufficiently long follow-up, cognitive dysfunction is likely to emerge and progress in a sizable proportion of patients. As multiple sclerosis advances, neurological and cognitive involvement tend to converge. Limitations in a patient's work and social activities are correlated with the extent of cognitive decline, independent of degree of physical disability.     

Capacity for financial decision making in multiple sclerosis

Introduction: Cognitive impairment often occurs in people with multiple sclerosis (MS), and dysfunction involving executive function, new learning, and working memory is especially common. Compromised activities of daily living are linked to this cognitive impairment, and people with MS are apt to be unemployed and struggle to manage domestic responsibilities. Financial decision making is an important activity of daily living, and no study has examined whether it is compromised by neuropsychological dysfunction in people with MS. Method: A battery of neuropsychological tests and a measure of financial decision making (Financial Capacity Instrument, FCI: Marson, D. C. 2001. Loss of financial capacity in dementia: Conceptual and empirical approaches. Aging, Neuropsychology, and Cognition, 8, 164–181) were administered to 50 participants (34 patients with MS and 16 cognitively healthy adults). Based on the neuropsychological test results, 14 patients were classified as having cognitive impairment, and 20 had no significant impairment. Results: The impaired MS patients performed significantly worse than unimpaired patients and the healthy comparison group on most financial tasks. The impaired group retained abilities to count money and display adequate financial judgment. Regression analyses showed that measures of mental flexibility and working memory correlated most strongly with performance on the FCI domains across groups. Conclusions: Cognitively impaired patients with MS have degraded financial skills, which are linked to executive function and working memory deficits.     

Cognitive impairment in multiple sclerosis

PURPOSE OF REVIEW: For a long time, cognitive impairment in multiple sclerosis patients has been considered less important than, for instance, physical disability. This is no longer true because of the crucial role that cognitive deficits play in the good day-to-day adjustment of patients. This review highlights recent progress made in this area. A special focus lies on studies investigating the neural correlates of cognitive impairment in multiple sclerosis patients as detectable by conventional, quantitative and functional magnetic resonance imaging. RECENT FINDINGS: Measures of information-processing speed appear to be the most robust and sensitive markers of cognitive impairment in multiple sclerosis patients. Recent studies demonstrate that single, predominantly speed-related cognitive tests may be superior to extensive and time-consuming test batteries in screening overall cognitive decline. Quantitative magnetic-resonance-imaging findings suggest the extent of subtle tissue damage in normal-appearing white and grey matter to correlate best with the severity of cognitive impairment in multiple sclerosis patients. SUMMARY: From neuropsychological test data, and findings from magnetic resonance imaging and functional magnetic resonance imaging it is evident that cognitive impairment in multiple sclerosis is not just the result of tissue destruction, but rather a balance between tissue destruction, tissue repair, and adaptive functional reorganization.     

Treatment of vascular dementia--evidence from clinical trials with cholinesterase inhibitors

Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. In addition, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment (VCI) and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitor agents used in AD. Controlled clinical trials with donepezil, galantamine and rivastigmine in VaD, as well as in patients with AD plus CVD, have demonstrated improvements in cognition, behavior and activities of daily living.     

Treatment of vascular dementia-evidence from clinical trials with cholinesterase inhibitors

Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. Also, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitors used in AD. Controlled clinical trials with donepezil, galantamine, and rivastigmine in VaD, as well as in patients with AD plus CVD, have demonstrated improvement in cognition, behavior and activities of daily living.     

An evaluation of the NINCDS-ADRDA neuropsychological criteria for the assessment of Alzheimer's disease: a confirmatory factor analysis of single versus multi-factor models

Neuropsychological test batteries are frequently used to assess the nature and severity of cognitive deficits among patients with early Alzheimer's Disease (AD) and related disorders. The NINCDS-ADRDA criteria are among the most widely used guidelines to diagnose dementia (McKhann et al.,1984). These criteria specify eight distinct areas of neuropsychological function that should be evaluated in patients with suspected cognitive impairment. Recent studies have suggested that neuropsychological deficits observed in AD may be explained by a single general factor related to memory deficits or to executive dysfunction. In contrast, the results of other investigations have indicated that multiple qualitatively different factors underlie cognitive abilities in AD. In the present study, we used confirmatory factor analysis to examine the structure of cognitive abilities in AD and to assess the extent to which single and multiple ability factors accurately represent neuropsychological test data obtained from patients with AD. Results indicated that the NINCDS-ADRDA model fit the data better than a single factor model. However, a more parsimonious model specifying memory, verbal abilities, visuospatial skills, executive function, and higher as well as lower functional activities of daily living fit the data better than the NINCDS-ADRDA model. These results have important theoretical and practical implications for diagnostic evaluation.     

An Evaluation of the NINCDS-ADRDA Neuropsychological Criteria for the Assessment of Alzheimers Disease: A Confirmatory Factor Analysis of Single Versus Multi-Factor Models

Neuropsychological test batteries are frequently used to assess the nature and severity of cognitive deficits among patients with early Alzheimers Disease (AD) and related disorders. The NINCDS-ADRDA criteria are among the most widely used guidelines to diagnose dementia (McKhann et al.,1984). These criteria specify eight distinct areas of neuropsychological function that should be evaluated in patients with suspected cognitive impairment. Recent studies have suggested that neuropsychological deficits observed in AD may be explained by a single general factor related to memory deficits or to executive dysfunction. In contrast, the results of other investigations have indicated that multiple qualitatively different factors underlie cognitive abilities in AD. In the present study, we used confirmatory factor analysis to examine the structure of cognitive abilities in AD and to assess the extent to which single and multiple ability factors accurately represent neuropsychological test data obtained from patients with AD. Results indicated that the NINCDS-ADRDA model fit the data better than a single factor model. However, a more parsimonious model specifying memory, verbal abilities, visuospatial skills, executive function, and higher as well as lower functional activities of daily living fit the data better than the NINCDS-ADRDA model. These results have important theoretical and practical implications for diagnostic evaluation.     

Acetylcholinesterase inhibitors in cognitive impairment in Huntington’s disease: A brief review

Huntington’s disease (HD) is a neurodegenerative disease associated with cognitive deficits. Cognitive dysfunction may be present in the early stages of the disease, even before the onset of motor symptoms. The cognitive dysfunction includes executive dysfunction, psychomotor symptoms, visuospatial deficits, perceptual deficits, memory loss and difficulty learning new skills. Acetylcholinesterase inhibitors have shown good effect in the treatment of other types of dementia and it is postulated that it might delay cognitive decline in HD. We reviewed the evidence for Acetylcholinesterase inhibitors in the treatment of cognitive decline and dementia associated with Huntington’s disease. We identified 6 articles that investigated the role of Acetylcholinesterase inhibitors for treatment of cognitive deficits in Huntington’s disease. Following the review, the authors concluded that there is limited evidence for the use of Acetylcholinesterase inhibitors for cognitive impairment in HD.     

Anosognosia: patients' distress and self-awareness of deficits in Alzheimer's disease

We aimed to study how patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) suffer from awareness of their deficits. Self-awareness was assessed using the Anosognosia Questionnaire for Dementia in 12 pairs of MCI outpatients and caregivers, 23 with mild AD, and 18 with moderate AD. The discrepancy between patient's and caregiver's evaluation (anosognosia) became greater as AD progressed. The predictors of patients' distress, shown by multiple linear regression analyses, were awareness of decline in intellectual or social functioning; self-awareness of deficits in remembering appointments in MCI; in remembering appointments, writing, mental calculation, and understanding the newspaper in mild AD; and in mental calculation and doing clerical work in moderate AD. Caregivers assumed the predictors of patients' distress differently: awareness of deterioration of memory in MCI and mild AD, and basic activities of daily living in moderate AD. Understanding patients' disability from patients' perspective is required for successful care.     

A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson''s disease.

A consecutive series of 105 patients with Parkinson's disease were examined for the presence of affective disorders, cognitive deficits, and impairments in activities of daily living (ADLs); 92 received the same evaluation 12 months after the initial examination. On the basis of the initial psychiatric findings, patients were divided into major, minor, and non-depressed groups. Patients with major depression showed a significantly greater cognitive decline, deterioration in ADLs, and further advance through the Hoehn and Yahr stages than patients with either minor depression or no depression.     

Neuroimaging studies of different cognitive profiles in Parkinson's disease

It is now clear that cognitive deficits exist even early in Parkinson's disease, having a significant impact on daily activities. However, the nature and the neural origins of cognitive dysfunction in PD are still under debate. Furthermore, a great heterogeneity seems to exist with respect to the cognitive profiles found in patients at the early stages of the disease, and these initial differences are likely predictive of distinct outcomes regarding the later occurrence of dementia. These include the early presence of Mild Cognitive Impairments, the nature and number of domains affected, as well as the occurrence of depression or apathy. Here, we will review studies involving anatomical and functional neuroimaging, and neuropsychological evaluation that have attempted to address these issues. Recommendations for future work will also be discussed.     

Long-term neurological complications after hypoxic-ischemic encephalopathy

Hypoxic-ischemic encephalopathy accompanying cardiac arrest is a common cause of long-term neurological dysfunction. With the improvement in prehospital emergency systems, larger numbers of people are resuscitated from cardiac arrests, although with the increased prospect of neurological sequelae. Neurological impairment after cardiac arrest is dependent on the degree of brain damage suffered during the arrest. Although the duration and severity of brain ischemia is often difficult to determine, clinicians are often faced with difficult issues related to predicting outcome related to awakening and long-term neurological deficits after the arrest. Neurological impairments range from mild cognitive deficits to severe motor and cognitive deficits that preclude independence in many activities of daily living. Several neurological syndromes have been described in patients who awaken from hypoxic-ischemic coma with lasting motor and cognitive deficits. This review will address many of the common syndromes after hypoxic-ischemic encephalopathy, including persistent vegetative states, seizures, myoclonus, movement disorders, cognitive dysfunction, and other neurological abnormalities.     

Anticholinesterasics in the treatment of cognitive impairment in multiple sclerosis

Neuropsychological impairment is a common manifestation in multiple sclerosis (MS) and is found in 40-60% of patients. The pattern of cognitive impairment in MS is characterized by difficulties in recent memory, sustained attention, executive functions and information processing speed. These cognitive deficits have a significant impact on the patients' daily activities. However, there is no specific treatment available at present for cognitive disorders in MS patients. Treatment with acetylcholinesterase inhibitors (AChEI) has shown a positive effect on cognitive functions of patients with Alzheimer's disease and other conditions such as Lewy Body dementia, subcortical vascular dementia and Parkinson's disease. In this paper we review the results from studies and clinical trials aiming to demonstrate that AChEI could be a potential treatment for cognitive disorders in MS patients. Finally, we discuss future issues to take into consideration for AChEI treatments in the context of MS.     

Risk factors for and management of cognitive dysfunction in multiple sclerosis

Cognitive impairment is common in multiple sclerosis (MS), especially when assessed by neuropsychological tests that emphasize mental processing speed, episodic memory, and some aspects of executive function. In this Review, we question why some MS patients develop severe impairment in cognitive abilities, while cognitive ability remains intact in others. We find that the heterogeneity in neuropsychological presentation among patients with MS reflects the influence of many factors, including genetics, sex, intelligence, disease course, comorbid neuropsychiatric illness, and health behaviors. Neuropsychological deficits are also robustly correlated with brain MRI metrics. Male patients with early evidence of cerebral gray matter atrophy are most prone to impairment, whereas high premorbid intelligence improves the neuropsychological prognosis. Routine evaluation of cognition is useful for helping patients to navigate problems related to activities of daily living and work disability and, if reliable methods are employed, cognitive decline can be detected and included among the many clinical signs of disease progression or treatment failure. Pharmacological treatments for neuropsychological impairment are on the horizon, although presently no firm medical indications exist for the condition.     

Self-reported executive dysfunction, neuropsychological impairment, and functional outcomes in multiple sclerosis

Although cognitive deficits are common in persons with multiple sclerosis (MS), the relationship between subjective complaints and objective impairment is sometimes obscured. To elaborate this issue, the present study examined the relationship between subjective complaints of dysexecutive syndrome, neuropsychological performance, and self-reported activities of daily living in 42 people with MS and 13 control participants. Regression analyses revealed that subjective complaints of impairment, measured by the Frontal Systems Behavior Scale (FrSBe), emerged as a significant predictor of neuropsychological deficit and poor adaptive function. Accordingly, subjective complaints of dysexecutive function in MS may serve as a potent indicator of cognitive and functional impairment. Implications for research and clinical practice are discussed.     

Neuropsychological aspects of childhood multiple sclerosis: an overview

While cognitive impairment, major depression, and fatigue have been well documented in adult patients with multiple sclerosis (MS), there is still little information regarding MS-associated cognitive disabilities in infants and adolescents who represent 3 to 5% of all MS cases. Recent studies show that cognitive decline related to MS profoundly interferes with academic success and psychosocial adjustment. Neuropsychological dysfunction affects quality of life more significantly than mere Expanded Disability Status Scale is able to reflect. We herein give an overview of the knowledge available to date. Affective and emotional disturbances together with other comorbidities interfering with cognition are also reviewed. Finally, possible suggestions and future directions for the assessment of cognitive capabilities in children with MS are envisioned.     

Demenz als Erstsymptom bei spät beginnender Multipler Sklerose

Cognitive impairment is meanwhile accepted as a well-known symptomatology affecting up to 60% of the patients even in the early disease course of multiple sclerosis (MS). After a longer duration the development of dementia is not unusual. However, cognitive dysfunction as the primary or only manifestation of MS is thought to be rare. We report on four elderly patients referred to the memory clinic of our psychiatric university hospital because of beginning dementia. All of them were found to have evidence of a chronic inflammatory CNS process compatible with the diagnosis of MS. At the beginning of their symptomatology all patients were older than 60 years . Just in one case, progressive gait disturbances beginning after cognitive decline contributed to restriction in the activities of daily living. Data of 239 cases of the literature were reviewed and revealed motor disturbances as the main initial symptom and often a primary progressive course with unfavourable prognosis in late onset MS. Until now dementia as the primary symptomatology has not been described in patients older than 60 years. Possibly MS as a differential diagnosis in dementia as well as cognitive impairment as an initial symptom of MS is under-recognized.