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Disease progression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study.

BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and behavioural outcomes in patients with VCI to patients with no cognitive impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi-centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients, 938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at baseline. Compared to people with NCI, of whom 20-40% showed progression based on cognitive and functional measures, those with VCI were more likely to progress (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed progression of affective symptoms (30%) than those with NCI (12%) or AD (15% p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most people with VCI show readily detectable progression by 30 months. Depressive symptoms were more common and more progressive in VCI than in Alzheimer's disease, whereas clinical evidence of progressive executive dysfunction was common in both AD and VCI.

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Clinical trials in HIV-associated cognitive impairment: cognitive and functional outcomes.

Cognitive and functional outcomes are of primary interest in the design of efficacy trials in HIV-associated cognitive impairment. In a longitudinal cohort study, weak associations were found between measures of cognitive performance and commonly used measures of daily functioning (mostly self-report measures) in HIV-infected individuals. Modifications of current functional scales or new functional instruments are needed to assess the clinical relevance of cognitive changes in clinical trials of HIV-associated cognitive impairment.

AIDS Dementia Complex↗

Prevalence and outcomes of vascular cognitive impairment. Vascular Cognitive Impairment Investigators of the Canadian Study of Health and Aging.

OBJECTIVE: To assess the importance of vascular cognitive impairment and its three subgroups (cognitive impairment, no dementia; vascular dementia; and AD with a vascular component) to the prevalence and burden of cognitive impairment in elderly people. BACKGROUND: Vascular lesions may produce a spectrum of cognitive changes. Omitting elderly patients whose cognitive impairment falls short of dementia (vascular cognitive impairment, no dementia) may give a falsely low indication of the prevalence and burden of disease. To test this proposition, we compared the rates of adverse outcomes for patients with no cognitive impairment, vascular cognitive impairment (and its subgroups), and probable AD. METHODS: The Canadian Study of Health and Aging is a prospective cohort study of 10,253 randomly selected community-dwelling and institution-dwelling respondents aged 65 years or older. In the community, all participants (n = 9,008) were screened for cognitive impairment; those who screened positive and a sample of those who screened negative received a clinical assessment (n = 1,659). All patients living in institutions received a clinical assessment (n = 1,255). Participants were reassessed 5 years after the original survey. RESULTS: Vascular cognitive impairment without dementia was the most prevalent form of vascular cognitive impairment among those aged 65 to 84 years. Rates of institutionalization and mortality for those with vascular cognitive impairment were significantly higher than those of people who had no cognitive impairment, and the mortality rate for patients with vascular cognitive impairment was similar to that of patients with AD. CONCLUSIONS: Failure to consider vascular cognitive impairment without dementia underestimates the prevalence of impairment and the risk for adverse outcomes associated with vascular cognitive impairment.

Age Distribution↗

Changes over time in memory, processing speed and clock drawing tests help to discriminate between vascular cognitive impairment, mild cognitive impairment and Alzheimer's disease.

Measures of cognitive change over time may help to better discriminate between mild cognitive impairment, Alzheimer's disease and vascular cognitive impairment than single assessments. Our hypothesis was that performance in processing speed and executive function would decline with mild cognitive impairment and Alzheimer's disease. Subjects included 36 controls, 18 cases with mild cognitive impairment, eight with vascular cognitive impairment and 24 with Alzheimer's disease who were tested on a cognitive battery at two episodes with a 12-month interval. Changes in performance were determined for each group with paired means tests. Controls improved in pattern comparison speed and the CLOX, a clock-drawing task to detect dysexecutive function. Those with vascular cognitive impairment declined in letter comparison speed, but improved in paragraph recall. Alzheimer's disease patients declined in CLOX and the Hopkins Verbal Learning Test. The mild cognitive impairment group showed no significant changes. Alzheimer's disease patients on treatment declined in Hopkins Verbal Learning Test, while those without treatment declined in The Placing Test and CLOX. Processing speed decline may be a marker of cerebrovascular disease, while decline in memory and executive function was more evident with Alzheimer's disease.

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Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: Early diagnosis of dementia is important for those who might benefit from treatment. We designed a brief comprehensive neuropsychological test battery to help differentiate control subjects from patients with mild cognitive impairment (MCI) and dementia. METHOD: The battery included tests of memory, attention, executive function, speed, perception and visuospatial skills. It was administered to subjects from the OPTIMA cohort: 51 controls, 29 with MCI, 60 with 'possible' or 'probable' Alzheimer's disease (AD) (NINCDS/ADRDA) and 12 with cerebrovascular disease (CVD). Mann-Whitney U tests were used to compare performance of controls with other diagnostic groups. The sensitivity and specificity of the tests were determined using Receiver Operating Characteristic curve analyses. The effects of age, gender and years of education on test performance were determined with Spearman's rank correlations. RESULTS: The AD group performed worse than controls on all tests except an attention task. The Hopkins Verbal Learning Test and The Placing Test for episodic memory showed significant discriminative capacity between controls and other groups. Attention and processing speed tests discriminated CVD from controls. Category fluency, episodic memory tests and the CLOX test for executive function distinguished MCI from AD. Spearman's correlations showed negative associations between age and processing speed. Years of education affected performance on all tests, except The Placing Test. CONCLUSIONS: Certain neuropsychological tests have been shown to be sensitive and specific in the differential diagnosis of various types of dementia and may prove to be useful for detection of MCI.

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[Risk factors for cognitive impairment].

Cognitive impairment is an invalidating condition and its prevalence increases significantly with age. It is very important to identify the risk factors for cognitive impairment. Aside from age, sex, familiary history and educational level, the other major risk factors (hypertension, hypercolesterolemia, diabetes mellitus and tobacco), known to be associated frequently with different cerebrovascular diseases, might also contribute to degenerative forms of cognitive impairment because they might favour cerebral microvascular alterations with hypoperfusion, demyelinization and ischemic lesions of subcortical white matter. Longitudinal epidemiological studies detected that arterial hypertension, hypercolesterolemia and tobacco are frequently associated with degenerative forms of cognitive impairment. Some studies show there is no relationship between cognitive impairment and diabetes mellitus, while other underline its role; light alcohol drinking might protect against cognitive impairment. Other recently identified risk factors might be hyperhomocysteinemia and high C-reactive protein blood levels because they seem to be associated with cognitive impairment.

Age Factors↗

Vascular cognitive impairment.

Cognitive impairment commonly accompanies clinical syndromes associated with vascular disease of the brain. Because of evolving definitional criteria, however, the frequency of cognitive impairment attributable to cerebrovascular disease is difficult to determine. Dementia occurs in up to one-third of elderly patients with stroke, a subset of whom have Alzheimer's disease (AD) rather than a pure vascular dementia syndrome. In fact, pure vascular dementia has been shown to be uncommon in most large autopsy series. A mixed etiology of AD and cerebrovascular disease is thought to become more common with increasing age, although no clinical criteria for the diagnosis of AD with cerebrovascular disease are currently available. Epidemiological studies have implicated subcortical small-vessel disease as a risk factor for cognitive impairment and dementia, but the cognitive expression and clinical significance of MRI white matter changes in individual patients is difficult to establish. The frequency of specific neuropathologic features of vascular cognitive impairment depends largely on study inclusion criteria. Cerebral meningocortical microangiopathies with distinctive clinicopathological profiles are associated with dementia in both sporadic cases and familial syndromes. In patients with AD, the contribution of amyloid-beta protein to the degree of cognitive impairment has not been clearly defined.

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Which mini-mental state exam items can be used to screen for delirium and cognitive impairment?

Cognitive impairment is common in palliative care patients, but it is frequently undetected. The clinical consequence is that psychiatric states such as delirium, which often present with cognitive impairment, are inadequately treated. A short and simple questionnaire for screening of cognitive impairment is required for these patients, in order to proceed with more advanced testing if necessary. In this study, we explored the results from two samples of patients (n=290 and n=217) who had completed the Mini-Mental State Examination (MMSE). Cases of cognitive impairment are considered indicated by an MMSE score of less than 24 of the total 30. We found that caseness could be fairly accurately screened by using four of the original 20 MMSE items, and that a six-item questionnaire further greatly improved the discrimination.

Adult↗

The use of laboratory tests in patients with mild cognitive impairment.

Cognitive decline in elderly people can be caused by a specific and treatable metabolic disorder, and the use of laboratory tests is recommended as part of the diagnostic workup of patients with dementia. Patients with mild cognitive impairment (MCI) are commonly investigated by a similar laboratory diagnostic workup, however it is not known whether this clinical practice is justified. In the present study, we compared the frequencies of laboratory abnormalities, and laboratory abnormalities relevant for cognitive impairment, in consecutive patients with MCI or dementia (all types) observed in a memory clinic setting. As much as 55.1% of patients with MCI and 60.0% of patients with dementia had at least one abnormal laboratory value (a non-significant difference). The most frequent abnormal analysis was the serum cholesterol, that was high in 28.8% of patients with MCI and in 20.4% of patients with dementia. It was possible to detect, both in patients with MCI (1.5% and in patients with dementia (3.5%, a non-significant difference), abnormal metabolic values, indicating poorly controlled diabetes, renal failure, hyponatremia, folate or vitamin B12 deficiency and hyperthyroidism, which correction led to clinical improvement. The majority (62.5% of these alterations were previously unknown. These findings give support to the use of the laboratory diagnostic workup of dementia in patients with mild cognitive impairment.

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Medication use patterns among demented, cognitively impaired and cognitively intact community-dwelling elderly people.

OBJECTIVE: To determine whether medication use patterns in community-dwelling elderly people vary with level of cognitive function-dementia, cognitive impairment (but not dementia) and intact cognition. DESIGN: Cross-sectional survey. SETTING: A five-county area of central North Carolina, USA. PARTICIPANTS: 520 members of the Duke Established Populations for Epidemiologic Studies of the Elderly. MEASUREMENTS: Medication use in the previous 2 weeks was ascertained during a interview in the patient's home and was coded as to prescription and therapeutic class status. Cognitive status, the primary independent variable, was divided into: (i) dementia (n=100); (ii) cognitive impairment but not dementia (n=117); and (iii) cognitively intact (n=303). The dependent variables were any prescription or over-the-counter (OTC) medication use (vs non-use); number of prescription or OTC medications used; and prescription and OTC use combined within major therapeutic classes. Multivariate analyses controlled for socio-demographic characteristics, health status, functional status and access to health care. RESULTS: The use of any prescription medication was similar in the three groups. The demented were significantly less likely than cognitively impaired people to use any OTC medications (OR=0.65, 95% CI=0.45, 0.93), cardiovascular medications (OR=0.70, 95% CI=0.49, 0.99) and analgesics (OR=0.54, 95% CI=0.39, 0.75). As a combined group, those who were demented and cognitively impaired were less likely than the cognitively intact group to use any OTC medications (OR=0.78, 95% CI 0.65, 0.92). Compared with the cognitively impaired subjects, the demented group took fewer prescription medications (beta coefficient=-0.31, 95% CI=-0.59, -0.03) and similar numbers of OTC medications. Compared with those who were cognitively intact, the combined group of demented and cognitively impaired subjects took fewer OTC medications (beta coefficient=-0.14, 95% CI=-0.23, -0.05) and similar numbers of prescription medications. CONCLUSION: Increasing level of cognitive dysfunction is associated with decreased use of OTC, cardiovascular and analgesic medications and the use of fewer prescription medications. These results suggest important differences in medication use patterns among community-dwelling elderly people who vary in cognitive status.

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Associations between dementia/mild cognitive impairment and cognitive performance and activity levels in youth.

OBJECTIVES: To study the associations between dementia/mild cognitive impairment (MCI) and cognitive performance and activity levels in youth. DESIGN: Retrospective cohort study. SETTING: Research volunteers living throughout the United States. PARTICIPANTS: A total of 396 persons (mean age 75) who were graduates of the same high school in the mid-1940s. MEASUREMENTS: Adolescent intelligence quotient (IQ) scores were gathered from archived student records, and activity levels were determined from yearbooks. A two-stage telephone screening procedure (Modified Telephone Interview for Cognitive Status or Informant Questionnaire on Cognitive Decline in the Elderly followed by Dementia Questionnaire) was used to determine adult cognitive status. Data were analyzed using logistic regression to model the risk of cognitive impairment (dementia/MCI) versus no cognitive impairment as a function of IQ and activity level, adjusting for sex and education. RESULTS: High adolescent IQ and greater activity level were each independently associated with a lower risk for dementia/MCI (odds ratio (OR) for a 1-standard deviation increase in IQ=0.51, 95% confidence interval (CI)=0.32-0.79; OR for a unit increase in activity=0.32, 95% CI=0.12-0.84). No association was found between sex or education and adult cognitive status in this model. CONCLUSION: High IQ and greater activity levels in youth reduce the risk for cognitive impairments in aging. The mechanism(s) underlying these associations are unknown, but intelligence may be a marker for cognitive/neurological "reserve," and involvement in activities may contribute to "reserve." Early neuropathology and ascertainment bias are also possible explanations for the observed associations.

Adolescent↗

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

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A 12-week, open trial of donepezil hydrochloride in patients with multiple sclerosis and associated cognitive impairments.

Cognitive dysfunction occurs in up to 65% of patients with multiple sclerosis (MS), but there is no effective treatment for the symptoms. The authors conducted a 12-week, open-pilot study to assess the efficacy and tolerability of donepezil HCl administered in patients with MS and cognitive impairment. Seventeen patients at a long-term care facility with Mini-Mental State Examination scores of < or = 25 received 5 mg of donepezil HCl for a 4-week period, followed by 8 weeks of 10 mg of donepezil HCl. Cognitive, neurologic, functional, and behavioral assessments were conducted at baseline and at 4 and 12 weeks. Statistically significant improvement was observed in several cognitive domains including attention, memory, and executive functioning, as well as different aspects of behavior. These data suggest that donepezil HCl merits further study as a potentially viable treatment option for patients with cognitive impairment associated with MS.

Adult↗

Psychometric evaluation of selected pain intensity scales for use with cognitively impaired and cognitively intact older adults.

The purpose of this study was to determine the reliability and validity of selected pain intensity scales such as the Faces Pain Scale (FPS), the Verbal Descriptor Scale (VDS), the Numeric Rating Scale (NRS), and the Iowa Pain Thermometer (IPT) to assess pain in cognitively impaired older adults. A descriptive correlational design was used, and a convenience sample of 66 volunteers age 60 and older residing in assisted living facilities in the South was recruited for this study. The sample included 22 (33%) men and 44 (67%) women, with a mean age of 76. Ninety-eight percent (65) of the sample comprised Caucasian participants, with the exception of 1 African-American man. Seventy percent (47) completed high school and/or college. The mean Mini Mental State Exam (MMSE) score was 16, with a range of 1 to 29. Eighty-five percent scored 24 or lower, indicating some degree of cognitive impairment. The remaining 15% were cognitively intact. All but one participant could use each scale to rate their pain. Concurrent validity of the VDS, NRS, and IPT was supported with Spearman rank correlation coefficients ranging from .78 to .86 in the cognitively impaired group. The FPS, however, demonstrated weak correlations with other scales when used with the impaired group, ranging from .48 to .53. In the cognitively intact group, strong correlations ranging from .96 to .97 were found among all of the scales. Test-retest reliability at a 2-week interval was acceptable in the cognitively intact group (Spearman rank correlations ranged from .67 to .85) and unacceptable for most scales in the cognitively impaired group (correlations ranged from .26 to .67). When asked about scale preference, both the cognitively impaired and the intact groups preferred the IPT and the VDS. This study revealed that cognitive impairment did not inhibit participants' ability to use a variety of pain intensity scales, but the stability issue must be considered.

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Leg length, cognitive impairment and cognitive decline in an African-Caribbean population.

BACKGROUND: Shorter leg length is associated with an adverse environment in early childhood and has been found to be associated with a variety of disorders occurring in mid- to late-life, including dementia in a Korean population. In a community population of African-Caribbean elders, in whom leg length had been measured, we sought to compare associations with cognitive impairment at baseline and cognitive decline over a three-year follow-up period. METHODS: Of 290 African-Caribbean residents in south London recruited at baseline, 216 (74%) were re-interviewed after a three-year period and 203 had sufficient data for this analysis. Cognitive impairment was derived as a binary category from a battery of cognitive tests administered at baseline and cognitive decline was derived from change in performance on a subset of these tests. Leg length (iliac crest to lateral malleolus) was also measured. RESULTS: Shorter leg length was associated with female sex, lower occupational social class and reported hypertension and diabetes. Shorter leg length (lowest quartile) was significantly associated with cognitive impairment but there were no apparent associations with cognitive decline. The association with cognitive impairment was independent of age, sex and education. Social class appeared to be an important mediating factor. CONCLUSIONS: Shorter leg length may be a marker of early life stressors which result in reduced cognitive reserve. Interestingly this association was mediated more strongly by social class (previous occupational status) than by education in this population.

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