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Biomedical subjects

D Mungas

Publications and source records attributed to D Mungas.

At least 19 recordsLinked to original sources

Longitudinal volumetric MRI change and rate of cognitive decline.

OBJECTIVE: To examine how baseline and change of volumetric MRI relate to cognitive decline in older individuals. BACKGROUND: Memory is associated with hippocampal integrity, whereas executive function has been linked to impaired frontal lobe function. Previous studies have shown that hippocampal and cortical atrophy are more strongly related to cognition than are measures of subcortical cerebrovascular disease (CVD). The authors hypothesized that memory (MEM) decline would be related to change in hippocampal volume (HC), whereas decline in executive function (EXEC) would be related to change of cortical gray matter volume (CGM) and measures of subcortical CVD. METHODS: Subjects from a multicenter study (n = 103) included cognitively normal, mildly impaired, and demented cases with and without subcortical lacunes. All had longitudinal cognitive evaluation (mean = 4.8 years) and two or more MRI scans at least one year apart (mean = 3.4 years). MRI measures included HC, CGM, total lacune volume (LAC), and white matter hyperintensity volume (WMH). Random effects modeling of longitudinal data assessed effects of MRI baseline and MRI change on baseline and change of psychometrically matched measures of MEM and EXEC. RESULTS: Change in MEM was related to HC baseline and HC change. Change in EXEC was related to baseline CGM and to change in CGM, HC, and LAC. Results were unchanged when demented cases were excluded. WMH was not associated with change in MEM or EXEC independent of HC, CGM, and LAC. CONCLUSION: Hippocampal volume was the primary determinant of memory decline, whereas executive function (EXEC) decline was related to multiple brain components. Results support a hypothesis that MEM decline is strongly influenced by Alzheimer disease (AD), whereas EXEC decline may be complexly determined by cerebrovascular disease and AD.

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White matter lesions impair frontal lobe function regardless of their location.

OBJECTIVE: To analyze the effect of white matter lesions in different brain regions on regional cortical glucose metabolism, regional cortical atrophy, and cognitive function in a sample with a broad range of cerebrovascular disease and cognitive function. METHODS: Subjects (n = 78) were recruited for a study of subcortical ischemic vascular disease (SIVD) and Alzheimer disease (AD) contributions to dementia. A new method was developed to define volumes of interest from high-resolution three-dimensional T1-weighted MR images. Volumetric measures of MRI segmented white matter signal hyperintensities (WMH) in five different brain regions were related to regional PET glucose metabolism (rCMRglc) in cerebral cortex, MRI measures of regional cortical atrophy, and neuropsychological assessment of executive and memory function. RESULTS: WMH was significantly higher in the prefrontal region compared to the other brain regions. In all subjects, higher frontal and parietal WMH were associated with reduced frontal rCMRglc, whereas occipitotemporal WMH was only marginally associated with frontal rCMRglc. These associations were stronger and more widely distributed in nondemented subjects where reduced frontal rCMRglc was correlated with WMH for all regions measured. In contrast, there was no relationship between WMH in any brain region and rCMRglc in either parietal or occipitotemporal regions. WMHs in all brain regions were associated with low executive scores in nondemented subjects. CONCLUSIONS: The frontal lobes are most severely affected by SIVD. WMHs are more abundant in the frontal region. Regardless of where in the brain these WMHs are located, they are associated with frontal hypometabolism and executive dysfunction.

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Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia.

BACKGROUND: Mild cognitive impairment (MCI) is widely viewed as the transition phase between normal aging and Alzheimer disease (AD). Given that MCI can also result from cerebrovascular disease (CVD), the authors used clinical, MRI, and cognitive measures of AD and CVD to test the hypothesis that CVD increases the likelihood of progression from MCI to dementia within 3 years. OBJECTIVE: To examine the impact of CVD on progression of MCI to dementia. METHODS: Fifty-two consecutive patients with MCI (71% men) including many with symptomatic CVD were longitudinally evaluated for 3.1 +/- 1.3 years. MCI was defined as a Clinical Dementia Rating Scale (CDR) score of 0.5. Dementia was defined as progression to a CDR score of > or =1.0. RESULTS: Forty-four percent of the MCI patients had MRI infarcts, 50% of which were symptomatic. Thirty-three percent of patients progressed to dementia, and 37.8% of these had MRI infarcts. Clinically probable or possible AD was diagnosed in approximately 82% of converters. Of the clinical and MRI measures, only hippocampal volume was associated with increased risk to progression (hazard ratio [HR] = 0.31 [95% CI 0.1 to 0.92], p = 0.03). When neuropsychological measures were included in the analysis, memory (HR = 0.90 [95% CI 0.84 to 0.96], p = 0.002) and executive function (HR = 0.96 [95% CI 0.92 to 1.0], p = 0.045) were associated with increased risk of dementia progression, whereas APOE genotype, cerebrovascular risk factors, clinical stroke, presence or absence of lacunes, and extent of white matter hyperintensities did not predict progression. CONCLUSION: Within a heterogenous group of MCI patients, including many with clinically significant CVD, baseline memory and executive performance significantly predicted likelihood to develop dementia.

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Higher atrophy rate of entorhinal cortex than hippocampus in AD.

OBJECTIVES: To determine if atrophy rates were higher for entorhinal cortex (ERC) than for hippocampus in Alzheimer disease (AD), to determine the relationship between hippocampal atrophy rate and memory impairment, and to compare atrophy rates of ERC and hippocampus in differentiating between patients with AD and cognitively normal (CN) controls. METHODS: Twenty patients with AD and 25 CN subjects had MRI scans and clinical evaluations twice approximately 1.9 years apart. ERC volumes were measured manually and hippocampal volumes were measured semiautomatically on volumetric T1-weighted MR images. RESULTS: In AD, the atrophy rate of ERC (7.1 +/- 3.2%/year) was higher (p < 0.02) than that of hippocampus (5.9 +/- 2.4%/year). Furthermore, memory deficit in mild AD, measured with the Delayed List Verbal Recall test, correlated significantly with atrophy rates of both ERC (r = -0.61) and hippocampus (r = -0.59). Atrophy rates of ERC and hippocampus were comparable in differentiating between AD and CN. Using atrophy rates of ERC or hippocampus to detect a 20% treatment effect with 90% power (p < 0.05) would require about 100 completed patients per arm in a 2-year study. CONCLUSION: The finding in AD that the atrophy rate in the entorhinal cortex is higher than in the hippocampus is consistent with the view that AD pathology begins in the entorhinal cortex.

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Atrophy rates of entorhinal cortex in AD and normal aging.

OBJECTIVES: To explore the atrophy rate of entorhinal cortex (ERC) in AD and normal aging and assess the value of rate measurement of ERC atrophy for classifying subjects with AD from cognitively normal (CN) control subjects. METHODS: Twenty-one AD patients and 23 CN subjects had MRI scans and clinical evaluations twice within 1.8 +/- 0.6 years. ERC volumes were manually measured on volumetric T1-weighted MR images. RESULTS: Patients with AD had a greater annual percentage volume change of ERC than CN subjects on both sides (left: 6.8 +/- 4.3%/year for AD vs 1.4 +/- 2.5%/year for CN [F(1,42) = 25.6, p < 0.001]; right: 6.3 +/- 3.3%/year for AD vs 1.4 +/- 2.3%/year for CN [F(1,42) = 25.6, p < 0.001]). Furthermore, increased ERC atrophy rate was correlated (r = -0.56, p = 0.01) with decreased memory performance in AD. CN subjects had on average annual ERC atrophy rates greater than zero (p < 0.01). Baseline volume of ERC predicted atrophy rate of ERC (left: r = -0.53, p < 0.01; right: r = -0.42, p < 0.05) in CN subjects but not in AD subjects. Using ERC baseline volumes alone resulted in 77% overall correct classification (p < 0.01) between AD and CN subjects, with 76% sensitivity and 78% specificity and an area under receiver operator characteristic (ROC) curve of 0.83. Adding annual atrophy rate of ERC to the model accounted for most of the variance (p < 0.01), diminishing contributions from baseline volume and yielding 82% overall classification, with 76% sensitivity and 86% specificity and an area under the ROC curve of 0.93. CONCLUSION: ERC volume loss over time may be a better indicator for AD than cross-sectional measurements.

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Preliminary evidence that estrogen protects against age-related hippocampal atrophy.

Few studies have examined gender differences in hippocampal volumes, and the potential effect of estrogen on these measures has not been well studied. We used MRI to measure hippocampal volumes in elderly Mexican American men and women subjects in order to determine if there were gender differences and if estrogen replacement therapy (ERT) had an effect on hippocampal volume in postmenopausal women. MRI measures of hippocampal volumes (normalized to intracranial volume) were compared in 59 women and 38 men. Further comparisons were made between men subjects, women subjects taking ERT, and women subjects not taking ERT. There were no significant effects of gender on normalized hippocampal volumes. However, women subjects taking ERT had larger right hippocampal volumes than women subjects not taking ERT and larger anterior hippocampal volumes than men subjects and women subjects not taking ERT. These findings suggest a neuroprotective effect of estrogen.

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Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease.

OBJECTIVE: To examine volumetric MRI correlates of longitudinal cognitive decline in normal aging, AD, and subcortical cerebrovascular brain injury (SCVBI). BACKGROUND: Previous cross-sectional studies examining the relationship between cognitive impairment and dementia have shown that hippocampal and cortical gray matter atrophy are the most important predictors of cognitive impairment, even in cases with SCVBI. The authors hypothesized that hippocampal and cortical gray matter volume also would best predict rate of cognitive decline in cases with and without SCVBI. METHODS: Subjects were recruited for a multicenter study of contributions to dementia of AD and SCVBI. The sample (n = 120) included cognitively normal, cognitively impaired, and demented cases with and without lacunes identified by MRI. Cases with cortical strokes were excluded. Average length of follow-up was 3.0 years. Measures of hippocampal volume, volume of cortical gray matter, presence of subcortical lacunes, and volume of white matter hyperintensity were derived from MRI. Random effects modeling of longitudinal data was used to assess effects of baseline MRI variables on longitudinal change in a measure of global cognitive ability. RESULTS: Cortical gray matter atrophy predicted cognitive decline regardless of whether lacunes were present. Hippocampal atrophy predicted decline only in those without lacunes. Neither lacunes nor white matter hyperintensity independently predicted decline. CONCLUSIONS: Results suggest that cortical atrophy is an index of disease severity in both AD and subcortical cerebrovascular brain injury and consequently predicts faster progression. Hippocampal volume may index disease severity and predict progression in AD. The absence of this effect in cases with lacunes suggests that this group is etiologically heterogeneous and is not composed simply of cases of AD with incidental stroke.

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Brain function and cognition in a community sample of elderly Latinos.

BACKGROUND: Previous studies using PET to measure cerebral glucose metabolism in AD have found metabolic reductions in the temporoparietal and posterior cingulate cortices in individuals with dementia and those at risk of developing it. This study was designed to extend this finding to individuals selected from a population-based cohort of Mexican Americans with a wide spectrum of cognitive ability. METHODS: A group of 93 individuals was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired, cognitively impaired but not demented (CIND), and demented. PET was performed with the tracer [(18)F]-fluorodeoxyglucose, and data were analyzed with both statistical parametric mapping and an atrophy-corrected volume of interest approach. RESULTS: Individuals with dementia had metabolic reductions that were most robust in the posterior cingulate cortex, whereas CIND subjects had less statistically robust reductions in the posterior cingulate cortex. Cingulate hypometabolism increased the risk of dementia and was a significant risk factor for dementia in logistic regression models that also incorporated MR measures of hippocampal volume and white matter hyperintensities. CONCLUSION: Posterior cingulate cortical hypometabolism is clearly detected in individuals with dementia who are selected from a population with lower education and a high prevalence of cerebrovascular risk factors, supporting the generalizability of this finding. These metabolic reductions occur prior to the onset of dementia but only in those persons with relatively advanced symptoms.

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Brain structure and cognition in a community sample of elderly Latinos.

BACKGROUND: Previous studies have found that hippocampal atrophy and white matter hyperintensities (WMH) on MRI are linked to cognitive impairment and dementia. The authors measured these variables in a population-based cohort of older Mexican Americans with a wide spectrum of cognitive ability, ranging from normal cognition to dementia. OBJECTIVE: To investigate whether these structural brain changes were seen in individuals prior to the development of dementia and how these changes were related to the presence of dementia. METHODS: A sample of 122 subjects was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired (MI), cognitively impaired but not demented (CIND), and demented. Hippocampal volume was quantified using a region of interest approach. WMH was rated on a semiquantitative scale as the percent of total volume of white matter. RESULTS: Hippocampal volume was significantly reduced in CIND and demented individuals, and WMH were significantly increased in demented subjects. MI subjects did not have any significant changes in hippocampal volume or WMH. The risk for developing dementia was significantly and comparably increased in subjects with either hippocampal atrophy or high WMH. However, the risk for dementia increased dramatically in subjects with both hippocampal atrophy and a high degree of WMH. CONCLUSION: Reductions in hippocampal volume may be present before dementia but not until cognitive impairment is relatively severe. Because there is a synergistic effect between high WMH and hippocampal atrophy, interactions between vascular and degenerative processes may be important determinants of dementia.

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Executive dysfunction in subcortical ischaemic vascular disease.

BACKGROUND: Executive dysfunction has been reported in patients with subcortical-frontal pathology, even in the absence of dementia. OBJECTIVE: This study was undertaken to determine if impairments in executive functioning could be found in non-demented patients with subcortical lacunes. METHODS: Cross sectional comparison between older control subjects (n=27) and non-demented patients with one or more subcortical lacunes (n=12). All participants were administered a neuropsychological test battery incorporating three measures of executive functioning, the Stroop interference test, California card sorting test, and the initiation-perseveration subtest of the Mattis dementia rating scale. RESULTS: No group differences were found on measures of recent verbal memory, language, or spatial ability. Normal controls performed better than patients with lacunes in visual memory. On the Stroop interference test, patients with lacunes performed as well as controls on the colour naming condition but slower on the interference condition. Patients with lacunes also generated fewer correct sorts on the California card sort test and achieved lower scores on the initiation-perseveration subtest. Executive measures were correlated with extent of white matter signal hyperintensity but not number of lacunes. CONCLUSION: Subcortical ischaemic vascular disease is associated with subtle declines in executive functioning and visual memory, even in non-demented patients. The pattern of cognitive impairment after subcortical lacunes is consistent with models of subcortical-frontal circuits.

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MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease.

BACKGROUND: Causes of cognitive impairment in subcortical ischemic vascular disease (SIVD) are less well understood than in AD, but have been thought to result from direct effects of subcortical lacunes and white matter lesions, perhaps related to disruption of important cortical-subcortical pathways. OBJECTIVE: To examine the relation between cognitive abilities and quantitative MRI measures of subcortical cerebrovascular disease and cortical and hippocampal atrophy. METHODS: Subjects were 157 participants in a multicenter study of SIVD and AD who included cognitively normal, cognitively impaired, and demented individuals with and without subcortical lacunar infarcts. Dependent variables were neuropsychological tests of global cognitive function, memory, language, and executive function. Independent variables were quantitative MRI measures of volume of lacunar infarcts in specific subcortical structures, volume of white matter lesion (WML), volume of cortical gray matter (cGM), and total hippocampal volume (HV). Multiple regression analyses were used to identify MRI predictors of cognition. RESULTS: Subcortical lacunes were not related to cognitive measures independent of effects of other MRI variables. WML was independently related to selected, timed measures. HV and cGM were strong and independent predictors of cognitive variables, with effects that did not differ in subjects with and without subcortical lacunes. CONCLUSIONS: Results suggest that cognitive impairment associated with subcortical ischemic vascular disease is primarily a result of associated hippocampal and cortical changes.

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Frontal lobe hypometabolism predicts cognitive decline in patients with lacunar infarcts.

BACKGROUND: A proportion of patients with subcortical lacunes will suffer progressive cognitive dysfunction, but the basis for this decline is controversial and little is known about predicting cognitive decline in these patients. Studies of Alzheimer disease have shown that imaging measures of temporal and parietal metabolism and blood flow predict disease course. OBJECTIVE: To determine whether regional cerebral glucose metabolism predicts cognitive decline by testing 2 opposing hypotheses: (1) temporoparietal activity predicts decline (based on the idea that concomitant Alzheimer disease causes decline) vs (2) frontal hypometabolism predicts decline (based on evidence that subcortical frontal circuits are especially vulnerable to small vessel ischemia). DESIGN: Prospective cohort study. SETTING: University outpatient dementia center. PATIENTS: A convenience sample of 26 patients with radiologically defined lacunes and baseline cognitive function ranging from normal to moderately demented. MAIN OUTCOME MEASURES: Regional cerebral metabolism was quantitated in the form of atrophy-corrected positron emission tomographic activity ratios in cortical regions that were defined a priori. Patients were followed up at a mean of 1.8 years, and the dependent variable was rate of change in the Mini-Mental State Examination score. RESULTS: Bilateral and right hemisphere dorsolateral frontal metabolism significantly predicted cognitive decline, with right dorsolateral frontal metabolism explaining 19% of the variance. No other positron emission tomographic region was a significant predictor, nor were demographic variables or baseline Mini-Mental State Examination scores significant predictors. CONCLUSION: Cognitive decline in patients with lacunes may result in part from progressive vascular compromise in subcortical frontal circuits.

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The effects of age on rate of progression of Alzheimer disease and dementia with associated cerebrovascular disease.

BACKGROUND: Relatively little is known about how cerebrovascular disease affects progression of dementia. Previous studies have found no differences in progression of Alzheimer disease and vascular dementia, but these studies have not specifically examined age effects. OBJECTIVE: To test whether the rate of cognitive decline is different in Alzheimer disease compared with dementia with associated cerebrovascular disease in clinical and autopsy patient series. PATIENTS AND METHODS: We studied the longitudinal course of cognitive function as measured by the Mini-Mental State Examination (MMSE) in patients with clinically and neuropathologically diagnosed conditions evaluated through a university Alzheimer disease center. Clinical patients were grouped according to possible Alzheimer disease without stroke (n = 37), probable Alzheimer disease without stroke (n = 181), and dementia with stroke (n = 50). Autopsy cases were categorized into Alzheimer disease (n = 78) and dementia with vascular disease (n = 13). Data were analyzed using random-effects modeling of longitudinal change. RESULTS: There was a significant interaction between age and diagnosis in determining rate of change on the MMSE scores for both the clinical and autopsy samples. Rate of change decreased slightly with advancing age for Alzheimer disease groups, but increased with age for dementia with cerebrovascular disease groups. CONCLUSIONS: Dementia with cerebrovascular disease declined faster in patients 80 years and older compared with Alzheimer disease without associated cerebrovascular pathological conditions, but showed slower decline in patients younger than 80 years. This effect most likely reflects combined Alzheimer and vascular pathological conditions in older patients with cerebrovascular disease.

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A new verbal learning and memory test for English- and Spanish-speaking older people.

Word-list verbal learning and memory tests with appropriate normative data can be highly sensitive to cognitive decline, but there are significant limitations of such tests available for use with older Hispanic and non-Hispanic people living in the US. The purpose of this study was to (1) create a new word-list learning and memory test in both English and Spanish and, (2) validate it with respect to sensitivity to cognitive impairment, and (3) develop statistical corrections for the effects of significant demographic variables, including ethnicity, language of administration, age, education, and gender. A community dwelling sample of 801 English- and Spanish-speaking older people was employed. Recall on learning trials and the delayed recall trial of the word-list learning test were strongly related to the Mini-Mental State Examination (MMSE). moderately related to age, and weakly related to gender and education. The relationship of word-list variables and the MMSE did not significantly differ across ethnicity/language groups. Regression coefficients for demographic variables were used in a statistical correction formula to adjust raw word-list scores, and then to develop specific percentile cut-off values.

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Clinical criteria for the diagnosis of vascular dementia: a multicenter study of comparability and interrater reliability.

BACKGROUND: Several clinical criteria have been developed to standardize the diagnosis of vascular dementia (VaD). Significant differences in patient classification have been reported, depending on the criteria used. Few studies have examined interrater reliability. OBJECTIVE: To assess the concordance in classification and interrater reliability for the following 4 clinical definitions of VaD: the Hachinski Ischemic Score (HIS), the Alzheimer Disease Diagnostic and Treatment Centers (ADDTC), National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). METHODS: Structured diagnostic checklists were developed for 4 criteria for VaD, 2 criteria for Alzheimer disease (AD), and 4 criteria for dementia. Twenty-five case vignettes, representing a spectrum of cognitive impairment and subtypes of dementia, were prepared in a standardized clinical format. Concordance in case classification using different criteria and interrater reliability among 7 ADDTCs given a specific set of criteria was assessed using the kappa statistic. RESULTS: The frequency of a diagnosis of VaD was highest using the modified HIS or DSM-IV criteria, intermediate using the original HIS and ADDTC criteria, and lowest using the NINDS-AIREN criteria. Scores for interrater reliability ranged from kappa = 0.30 (ADDTC) to kappa = 0.61 (original HIS). CONCLUSIONS: Clinical criteria for VaD are not interchangeable. Depending on the criteria selected, the reported prevalence of VaD will vary significantly. The traditional HIS has higher interrater reliability than the newer criteria for VaD. Prospective longitudinal studies with clinical-pathological correlation are needed to compare validity.

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Development of psychometrically matched English and Spanish language neuropsychological tests for older persons.

Item response theory (IRT) methods were used to develop a neuropsychological test battery with matched English and Spanish language forms. Candidate items for 12 scales measuring core neuropsychological abilities were generated and administered to 200 community-dwelling elderly participants tested in Spanish and 208 tested in English. IRT methods were used to eliminate linguistically biased items and refine scales to assess broad ability ranges. Reasonably good psychometric matching of scales was achieved within and across English and Spanish language forms. All scales were sensitive to cognitive impairment as measured by the Mini-Mental State Examination (MMSE), with highly similar relationships between scale scores and MMSE across English and Spanish groups. The outcome supports the use of IRT methods in cross-cultural and multilingual test development and indicates that this strategy has potential for future neuropsychological test development.

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Affective behavioural disturbances in Alzheimer's disease and ischaemic vascular disease.

OBJECTIVES: To investigate affective change in Alzheimer's disease and ischaemic vascular disease and examine the contribution of white matter disease to psychopathology in these dementias. Based on earlier studies, it was predicted that: (1) depression would be more prevalent and severe in ischaemic vascular disease; (2) psychomotor slowing would be more prevalent in ischaemic vascular disease; (3) apathy would be more prevalent in ischaemic vascular disease; and (4) The degree of white matter disease would be positively correlated with the severity of psychomotor slowing. METHODS: Ratings of affective/behavioural states and white matter disease were compared in 256 patients with Alzheimer's disease and 36 patients with ischaemic vascular disease or mixed dementia with an ischaemic vascular component using analysis of variance (ANOVA) and linear regression models. RESULTS: The findings were: (1) decreased affect/withdrawal was more prevalent and severe in patients with ischaemic vascular disease and patients with white matter disease; (2) psychomotor slowing was more severe in patients with ischaemic vascular disease and patients with white matter disease; and (3) differences between Alzheimer's disease and ischaemic vascular dementia groups in the degree of psychomotor slowing were independent of the severity of white matter disease. CONCLUSIONS: Future studies using structural and functional neuroimaging techniques would be helpful for examining the relation between neurobiological factors and affective/behavioural disturbances in dementia.

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Depressive syndromes and functional disability in dementia.

The goals of this study were to assess (1) the prevalence of major and minor depression in Alzheimer's disease (AD), ischemic vascular dementia (IVD), and mixed dementia (AD/IVD); (2) demographic and clinical variables that may be associated with depression; and (3) the relationship between depression severity and the level of functional impairment and cognitive decline. Demographic variables, depression diagnoses, Mini-Mental State Examination scores, and Blessed Roth Dementia Rating Scale scores were compared in patients with AD (N = 582), IVD (N = 48), and mixed dementia (N = 61) using analysis of variance and linear regression models. Data were collected using standardized rating instruments at the time of the patients' initial evaluations at the University dementia clinics. The results were that (1) depression was related to lower education, (2) major depression was more prevalent in IVD compared to probable AD, and (3) functional impairment was greater in patients with minor or major depression compared to patients without depression. Our data suggest that the level of functional disability in dementia may be related to severity of depression. Additional studies are needed to validate our results and examine the contribution of additional neurobiologic factors to the pathophysiology of depression in dementia.

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