Biomedical subjects

Dan Mungas

Publications and source records attributed to Dan Mungas.

At least 19 recordsLinked to original sources

PubMed2006

Brain imaging evidence of preclinical Alzheimer's disease in normal aging.

OBJECTIVE: This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people. METHODS: We performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community-dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini-Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores. RESULTS: Six subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid-temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini-Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini-Mental State Examination decline. INTERPRETATION: These results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology.

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PubMed2006

Cognitive impact of subcortical vascular and Alzheimer's disease pathology.

OBJECTIVE: To assess the interactions among three types of pathology (ie, cerebrovascular disease, hippocampal sclerosis [HS], and Alzheimer's disease [AD]), cognitive status, and apolipoprotein E genotype. METHODS: We report clinicopathological correlations from 79 autopsy cases derived from a prospective longitudinal study of subcortical ischemic vascular disease and AD. RESULTS: Thirty percent of the cases had significant cerebrovascular parenchymal pathology scores (CVDPS), 54% had significant AD pathology, and 18% had HS. In an ordinal logistic regression analysis that included interaction terms to assess the effects of each pathological variable when the other variables are interpolated to zero, each of the three pathology variables contributed independently to cognitive status: Braak and Braak stage odds ratio (OR) = 2.84 (95% confidence interval, 1.81-4.45), HS score OR = 2.43 (95% confidence interval, 1.01-5.85), and CVDPS OR = 1.02 (95% confidence interval, 1.00-1.04). Only Braak and Braak stage contributed to a global neuropsychological measure of cognitive impairment. Apolipoprotein E4 genotype was associated with Braak and Braak stage (OR, 1.31 [95% confidence interval, 1.03-1.68]), but not CVDPS or HS scores. INTERPRETATION: In this convenience sample enriched for subcortical ischemic vascular disease, HS was a common unsuspected neuropathological finding. Apolipoprotein E4 genotype was associated with cerebral amyloid angiopathy, but not HS or arteriosclerosis. When Braak and Braak stage was interpolated to zero, both CVDPS and HS contributed to cognitive impairment. However, advancing stages of AD pathology overwhelmed the effects of CVDPS and HS, to become the major determinant of dementia.

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PubMed2005

Central obesity and the aging brain.

BACKGROUND: Central adiposity as an indicator of visceral fat is linked to vascular and metabolic factors that in turn are related to cognitive decline and dementia. OBJECTIVE: To determine whether larger waist-hip ratio (WHR) is associated with structural brain changes that underlie cognitive decline and dementia. DESIGN: Cross-sectional analysis of an epidemiologic cohort study of cognitive and functional decline (Sacramento Area Latino Study on Aging). SETTING: California Central Valley. PARTICIPANTS: A total of 112 individuals selected from an ongoing cohort study of 1789 older Latino individuals. Baseline anthropomorphic measures (WHR) and measurements of fasting blood glucose, cholesterol, and insulin levels and blood pressure were obtained. MAIN OUTCOME MEASURES: Baseline magnetic resonance images were analyzed quantitatively to determine the hippocampal volumes in the right and left hemispheres and rated for the percentage of white matter hyperintensities. RESULTS: Greater WHR (P = .02) and older age (P<.001) were negatively related to hippocampal volumes. The WHR and age were positively related to white matter hyperintensities (P = .02 and P = .001, respectively). A 1-SD increase in WHR was associated with a 0.2-SD decrease in hippocampal volume and a 27% increase in white matter hyperintensities. These relationships were not affected by adjustment for body mass index, total cholesterol, fasting blood glucose, and insulin levels or systolic blood pressure in the models. CONCLUSION: A larger WHR may be related to neurodegenerative, vascular, or metabolic processes that affect brain structures underlying cognitive decline and dementia.

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PubMed2005

Earlier onset of Alzheimer disease symptoms in latino individuals compared with anglo individuals.

BACKGROUND: Latino individuals are the largest minority group and the fastest growing population group in the United States, yet there are few studies comparing the clinical features of Alzheimer disease (AD) in this population with those found in Anglo (white non-Latino) patients. OBJECTIVE: To compare the age at AD symptom onset in Latino and Anglo individuals. DESIGN: Cross-sectional assessment using standardized methods to collect and compare age at AD symptom onset, demographic variables, and medical variables. SETTING: Five National Institute on Aging-sponsored Alzheimer's Disease Centers with experience evaluating Spanish-speaking individuals. PATIENTS: We evaluated 119 Latino and 55 Anglo patients who had a diagnosis of AD. MAIN OUTCOME MEASURE: Age at symptom onset. RESULTS: After adjusting for center, sex, and years of education, Latino patients had a mean age at symptom onset 6.8 years earlier (95% confidence interval, 3.5-10.3 years earlier) than Anglo patients. CONCLUSIONS: An earlier age at symptom onset suggests that US mainland Latino individuals may experience an increased burden of AD compared with Anglo individuals. The basis for the younger age at symptom onset remains obscure.

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PubMed2005

Correlates of hippocampal neuron number in Alzheimer's disease and ischemic vascular dementia.

The cornu ammonis 1 region of the hippocampus (CA1) sector of hippocampus is vulnerable to both Alzheimer's disease (AD)-type neurofibrillary degeneration and anoxia-ischemia. The objective of this article is to compare number and size of neurons in CA1 in AD versus ischemic vascular dementia. Unbiased stereological methods were used to estimate the number and volume of neurons in 28 autopsy-derived brain samples. For each case, the entire hippocampus from one cerebral hemisphere was sliced into 5mm slabs (5-7 slabs/case), cut into 50 microm sections, and stained with gallocyanine. Using the optical dissector, we systematically sampled the number and size of neurons throughout the extent of CA1 and CA2. The total number of neurons was significantly less in AD compared with ischemic vascular dementia (p < 0.02), but there was no significant difference in neuron size. The greatest loss of neurons was observed in two cases with combined AD and hippocampal sclerosis. Regardless of causative diagnosis, the number of CA1 neurons correlates with magnetic resonance imaging-derived hippocampal volume (r = 0.72; p < 0.001) and memory score (r = 0.62; p < 0.01). We conclude that although CA1 neuron loss is more consistently observed in AD than ischemic vascular dementia, severity of loss shows the expected correlation with structure and function across causative subtype. Reductions in magnetic resonance imaging-derived hippocampal volume reflect loss, rather than shrinkage, of CA1 neurons.

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PubMed2005

Degree of discrepancy between self and other-reported everyday functioning by cognitive status: dementia, mild cognitive impairment, and healthy elders.

BACKGROUND: Previous studies show individuals with dementia overestimate their cognitive and functional abilities compared to reports from caregivers. Few studies have examined whether individuals with Mild Cognitive Impairment (MCI) also tend to underestimate their deficits. In this study we examined whether degree of discrepancy between patient and informant-reported everyday functioning was associated with cognitive status. METHODS: The sample consisted of 111 ethnically diverse community-dwelling older adults (46 Caucasians and 65 Hispanic individuals), which was divided into four diagnostic categories: cognitively normal, MCI-memory impaired, MCI-nonmemory impaired, and demented. Everyday functional abilities were measured using both a self-report and informant-report version of the Daily Function Questionnaire (DFQ). A Difference Score was calculated by subtracting patients' DFQ score from their informants' score. RESULTS: DFQ Difference Scores were significantly higher in the demented group compared to normals and both of the MCI groups. However, the Difference Scores for the MCI groups were not significantly different than the normals. Further, while patient reported everyday functioning did not differ among the four diagnostic groups, informant reported functional status was significantly different across all diagnostic groups except MCI-nonmemory impaired vs normals. Performance on objective memory testing was associated with informant-rated but not patient-rated functional status. Demographic characteristics of the patients and informants, including ethnicity, had no association with the degree of discrepancy between raters. CONCLUSIONS: Although there may be some mild functional changes associated particularly with the MCI-memory impaired subtype, individuals with MCI do not appear to under-report their functional status as can often been seen in persons with dementia.

Activities of Daily Living↗

PubMed2005

A semantic verbal fluency test for English- and Spanish-speaking older Mexican-Americans.

Currently, there are few semantic verbal fluency tests available with appropriate and adequate normative data for older Latinos of Mexican ancestry. The purposes of this study were to examine the effects of language and socioeconomic variables on a semantic verbal fluency test, derive normative data and develop statistical corrections for the effects of significant variables. A large, community-dwelling sample of Latinos of primarily Mexican ancestry over age 60 was asked to name animals with four legs within 1 min in their preferred language of English or Spanish. The total sum of animals named was influenced by age, education, gender, and, to a much lesser extent, language of test administration. Regression coefficients derived from demographic variables were used to adjust raw scores in a general correction formula, and specific percentile cutoff values were identified for these adjusted scores. Normative data tables stratified on demographic variables are also presented.

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PubMed2005

Criterion-referenced validity of a neuropsychological test battery: equivalent performance in elderly Hispanics and non-Hispanic Whites.

This study examined the validity of the Spanish and English Neuropsychological Assessment Scales (SENAS) in comparison with clinical diagnosis of normal cognition versus cognitive impairment, not demented (CIND) versus demented in elderly Hispanics and Whites. Relationships between SENAS scales and diagnosis were essentially the same in Hispanics and Whites. Verbal memory measures were most strongly related, with more than 35% of the variance in these measures accounted for by diagnosis independent of effects of education, age, gender, and language. Diagnosis accounted for more than 10% of the variance (19% on average) in 11 of the 17 measures examined in this study. Logistic regressions showed that verbal memory was important both for distinguishing normal from CIND and CIND from demented. Object naming improved discrimination of CIND from demented beyond that of verbal memory alone. These results provide evidence of equivalent validity across Hispanics and Whites.

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PubMed2005

Spanish and English neuropsychological assessment scales: relationship to demographics, language, cognition, and independent function.

This study examined the relationship of the Spanish and English Neuropsychological Assessment Scales (SENAS) to demographic, cultural, and language fluency variables and to measures of cognition and independent functioning. Participants were 367 Hispanics and 160 Caucasians in the 60+ years age range, all living in the community. In Study 1, education and language use had strong influences on SENAS scores and largely explained ethnic group differences in mean scale scores. Age had weak effects on most scales except for verbal memory measures. Acculturation effects in Hispanics were largely accounted for by education and language use. Study 2 showed equivalent sensitivity of SENAS to cognitive and functional status in Hispanics and Caucasians. Results indicate that interpretation of SENAS scores must be informed by effects related to education and language fluency but provide evidence of equivalent validity in Hispanics and Caucasians with respect to concurrent measures of cognition and independent function.

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PubMed2004

Effects of white matter lesions and lacunes on cortical function.

BACKGROUND: Subcortical ischemic vascular dementia has been ascribed to prominent frontal lobe dysfunction secondary to ischemic lesions in frontothalamic circuits. Whether small-vessel disease in fact predominantly affects the frontal lobes is not well documented. OBJECTIVE: To investigate the effects of subcortical lesions (lacunes and white matter lesions [WML]) on cortical function, as reflected in glucose metabolism and cognitive function, in elderly individuals. DESIGN: Cross-sectional analyses of case series. SETTING: Multicenter, university-based study of subcortical vascular dementia. PATIENTS: Persons with normal cognition, mild cognitive impairment, or dementia and with and without lacunes on magnetic resonance images. MAIN OUTCOME MEASURES: Regional cerebral glucose metabolism, normalized regional metabolic activity, and neuropsychological test scores. Major hypotheses were that volume of lacunes and WML correlate selectively with hypometabolism of prefrontal cortex and failure of executive cognitive ability. RESULTS: Lacunes correlated with metabolic rates in dorsolateral frontal cortex (DLF); WML substantially reduced metabolic rates throughout cortex, most strongly so in DLF. When regional metabolic activity was normalized to whole brain activity, lacunes remained correlated with DLF activity, whereas the WML effect was no longer found, probably because of its general distribution. Regional cerebral glucose metabolism and normalized activity in DLF also correlated with cortical atrophy. Metabolic activity in DLF correlated with executive function, memory, and global cognitive function, while activity in middle temporal gyrus correlated with memory and global function but not executive function. CONCLUSIONS: The metabolic effects of lacunes and WML are most apparent in DLF, but the effects of WML are generalized and frontal hypometabolism correlates with memory and global impairment, cognitive as well as executive function. The effects of subcortical cerebrovascular disease appear to converge on the frontal lobes but are diffuse, complex, and of modest magnitude.

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PubMed2004

Everyday functioning in relation to cognitive functioning and neuroimaging in community-dwelling Hispanic and non-Hispanic older adults.

The purpose of this study was to examine how a specific informant-based measure of everyday functioning, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE; Jorm & Korten, 1988) relates to cognition and structural neuroimaging in a large multicultural, multilingual sample of Caucasians and Hispanics. Cognitive variables included selected subtests from the Spanish and English Neuropsychological Assessment Scales (SENAS; Mungas et al., 2000): Verbal Memory, Object Naming, Verbal Attention Span, Verbal Conceptual Thinking, and Pattern Recognition. The association between the IQCODE and selected neuroimaging variables, hippocampal volume and white matter hyperintensity, was evaluated in a subsample of English- and Spanish-speaking Hispanic individuals. The cognitive variables showed strong bivariate relationships with the IQCODE, although only Verbal Memory and Object Naming independently predicted level of functional ability. Verbal Memory was the strongest predictor of functional status, accounting for 23% of the variance in the IQCODE. White matter hyperintensity was also independently related to the IQCODE, accounting for 18% of the variance. Hippocampal volume was related to the IQCODE in a simple bivariate analysis, but was not an independent predictor of reported functional status after controlling for age. The relationships between cognitive variables and functional status, as well as between the imaging variables and the IQCODE, did not differ across language-ethnic groups.

Activities of Daily Living↗

PubMed2004

Correlates of memory function in community-dwelling elderly: the importance of white matter hyperintensities.

We sought to identify magnetic resonance- (MR)-imaged structures associated with declarative memory in a community-dwelling sample of elderly Mexican-American individuals with a spectrum of cognitive decline. Measured structures were the hemispheric volumes of the hippocampus (HC), parahippocampal gyrus, and remaining temporal lobes, as well as severity of white matter signal hyperintensities (WMH). Participants were an imaged subsample from the Sacramento Area Latino Study of Aging (SALSA), N = 122. Individuals were categorized as normal, memory impaired (MI), cognitively impaired non-demented (CIND), or demented. We show that WMH was the strongest structural predictor for performance on a delayed free-recall task (episodic memory) in the entire sample. The association of WMH with delayed recall was most prominent in elderly normals and mildly cognitively impaired individuals with no dementia or impairment of daily function. However, the left HC was associated with verbal delayed recall only in people with dementia. The right HC volume predicted nonverbal semantic-memory performance. We conclude that WMH are an important pathological substrate that affects certain memory functions in normal individuals and those with mild memory loss and discuss how tasks associated with WMH may rely upon frontal lobe function.

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PubMed2004

Hippocampal volume and retention in Alzheimer's disease.

This study tested the hypothesis that the hippocampus has a relatively specific role in retaining information over delays. Thirty-seven subjects with probable Alzheimer's disease were evaluated with a verbal memory task and structural MRI. Cortical gray matter but not hippocampal volume predicted immediate free recall. In contrast, hippocampal volume was the best predictor of how well information was retained over a delay, even after controlling for levels of immediate recall. Results suggest that the role of the hippocampus is relatively specific to the consolidation of new memories.

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PubMed2004

Spanish and English Neuropsychological Assessment Scales (SENAS): further development and psychometric characteristics.

The Spanish and English Neuropsychological Assessment Scales were devised to be a broad set of psychometrically matched measures with equivalent Spanish and English versions. Study 1 in this report used item response theory methods to refine scales. Results strongly supported psychometric matching across English and Spanish versions and, for most scales, within English and Spanish versions. Study 2 supported in both English and Spanish subsamples the 6-domain model of ability that guided scale construction. Study 3 examined differential item functioning (DIF) of one scale (Object Naming) in relation to education, ethnicity, gender, and age. Effects of DIF on scale-level ability scores were limited. Results demonstrate an empirically guided psychometric approach to test construction for multiethnic and multilingual test applications.

Cognition↗

PubMed2004

Forgetting in dementia with and without subcortical lacunes.

Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD) are common causes of dementia, often co-occur, and can present quite similarly, making differential diagnosis clinically challenging. This study tested the hypothesis that patients with SIVD retain information better than AD patients. Participants were 35 dementia patients with subcortical lacunes (SIVD group), 27 dementia patients without lacunar infarction (AD group), and 56 normal controls. Results indicated that despite comparable levels of initial acquisition, AD patients showed more rapid forgetting. Further analysis indicated that memory patterns within the SIVD group were heterogeneous, with some participants exhibiting rapid forgetting and some exhibiting good retention. SIVD participants with good retention showed a trend for greater executive impairments relative to SIVD participants with rapid forgetting and AD participants. Results suggest that rapid forgetting in SIVD may imply concomitant AD, whereas the dementia in patients with good retention may be purely vascular in origin. Three SIVD patients with rapid forgetting followed to autopsy all had AD pathology, further supporting the link between memory patterns and AD.

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PubMed2003

Psychometrically matched measures of global cognition, memory, and executive function for assessment of cognitive decline in older persons.

Item response theory methods were used to derive psychometrically sophisticated measures of global cognition, memory, and executive function. Goals were that these measures (a) could be derived from commonly used neuropsychological tests, (b) would have linear measurement properties, and (c) would be psychometrically matched. Scale development was based on a sample of 400 older individuals with cognitive function ranging from normal to demented. Scales were reasonably matched with linear measurement over an ability range relevant to many important clinical applications. Cognitively normal, mild impairment, and dementia participant groups differed on baseline measures and rate of decline. Association of measures with quantitative structural magnetic resonance imaging variables followed expected patterns. This approach to scale development may have applications for other neuropsychological assessment problems.

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PubMed2003

Neuropsychiatric symptoms in Latino elders with dementia or cognitive impairment without dementia and factors that modify their association with caregiver depression.

PURPOSE: The purpose of this study was to determine neuropsychiatric symptom frequency and intensity in demented and cognitively impaired but not demented Latino elderly persons, evaluate whether overall neuropsychiatric symptom intensity is associated with higher levels of caregiver depression, and identify factors that modify the relationship between neuropsychiatric symptoms and caregiver depression. DESIGN AND METHODS: Ninety-five elderly Latinos with dementia or cognitive impairment but not dementia (CIND), all of whom were identified through an ongoing epidemiological cohort study, and their informal caregivers participated in the study. Caregivers were interviewed in their homes, in either Spanish or English. The Neuropsychiatric Inventory was used to assess neuropsychiatric disturbances. RESULTS: For most neuropsychiatric symptoms, prevalence and intensity were significantly higher in the demented group compared with the CIND group. The overall neuropsychiatric symptom intensity score was significantly associated with caregiver depression. The strength and direction of the association of neuropsychiatric symptoms with caregiver depression was found to vary by three factors: whether the caregiver was the care recipient's spouse, whether the care recipient had dementia or CIND, and the care recipient's age. IMPLICATIONS: Neuropsychiatric symptoms may play a significant role in caregiver depression among Latino families. However, the impact of neuropsychiatric disturbances on Latino caregivers may differ depending on characteristics of both the caregiver and care recipient. The adverse impact of neuropsychiatric symptoms on caregivers of elderly persons with CIND has not been previously reported and deserves further study.

Age Distribution↗

PubMed2002

A verbal learning and memory test for English- and Spanish-speaking older Mexican-American adults.

Currently, there are significant limitations in word-list verbal learning and memory tests that are appropriate and have adequate normative data for use with older Latinos of Mexican descent. The purpose of this study was to derive normative data for a word-list learning test with English and Spanish versions, the Spanish English Verbal Learning Test (SEVLT), and develop statistical corrections for the effects of significant demographic variables. A large, population-based sample of 1,789 Latinos of primarily Mexican ancestry over age 60 was employed. Individual trial scores, the total number of items recalled in the learning trials, and the delayed recall trial of the SEVLT were influenced by age, education, gender, but not the language of SEVLT administration. Regression coefficients derived from demographic variables were used to adjust raw SEVLT scores in a general correction formula, and specific percentile cut-off values were identified for these adjusted scores. Normative data tables stratified on demographic variables are also presented.

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