Biomedical subjects

Bruce R Reed

Publications and source records attributed to Bruce R Reed.

15 recordsLinked to original sources

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

Age effects on atrophy rates of entorhinal cortex and hippocampus.

The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04+/-0.02% per year for ERC and 0.05+/-0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE epsilon4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials.

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PubMed2005

Different mechanisms of episodic memory failure in mild cognitive impairment.

Mild cognitive impairment (MCI), defined as episodic memory impairment beyond what is expected in normal aging, is often associated with hippocampal atrophy (HA) and may represent incipient Alzheimer's disease. However, recent studies suggest that MCI is very heterogeneous and multiple etiologies likely exist. One possibility is small vessel cerebrovascular disease (CVD). Specifically, we hypothesized that white matter hyperintensities (WMH), an MRI marker for CVD, would lead to impairments in executive control processes critical for working memory that may, in turn, result in episodic memory impairment. To test this hypothesis, we examined a group of subjects clinically diagnosed with MCI and used MRI to further subcategorize individuals as either MCI with severe white matter hyperintensities (MCI-WMH) or MCI with severe hippocampal atrophy (MCI-HA). MCI-WMH, MCI-HA, and matched control subjects each performed a battery of working memory and episodic memory tasks. Results showed that MCI-HA and MCI-WMH were equally impaired on the episodic memory task relative to controls, but MCI-WMH were additionally impaired on tests tapping verbal and spatial working memory abilities and attentional control processes. These results suggest that CVD and hippocampal dysfunction are associated with distinct neuropsychological profiles. Although both syndromes are associated with episodic memory deficits, CVD is additionally associated with working memory and executive control deficits.

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PubMed2005

White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy.

The goal of this study was to examine the relationship between subcortical vascular disease and brain atrophy in patients with Alzheimer's disease (AD) and mixed dementia (i.e., AD and subcortical vascular disease together). MRI was performed on 77 cognitively normal (CN) subjects, 50 AD and 13 mixed dementia patients. Subcortical vascular disease was determined by white matter hyperintensities (WMH) volume and presence of subcortical lacunes. Brain atrophy was measured using total brain cortical gray matter (CGM), entorhinal cortex (ERC) and hippocampal volumes. CGM volume, but not ERC or hippocampal volume was inversely related to WMH volume in patients and controls. In contrast, no relationship was detected between CGM, ERC, or hippocampal volumes and subcortical lacunes. Furthermore, no interaction was found between WMH and diagnosis on cortical atrophy, implying that WMH affect cortical atrophy indifferently of group. These results suggest that subcortical vascular disease, manifested as WMH, may affect cortical atrophy more than ERC and hippocampal atrophy. Further, AD pathology and subcortical vascular disease may independently affect cortical atrophy.

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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

Vascular dementia.

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Alzheimer Disease↗

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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PubMed2004

Clinical and neuropsychological features in autopsy-defined vascular dementia.

Studies reporting that ischemic vascular dementia (IVD), compared to Alzheimer's disease (AD), is associated with relatively greater impairment of executive function and relatively preserved episodic memory raise the question of whether there is a distinctive neuropsychological profile of impairment associated with IVD and whether this might be useful in clinical diagnosis. However, prior reports are almost all based on clinically diagnosed cases, raising obvious issues of possible circularity and leaving unanswered questions of validity. Here we report on clinical and neuropsychological findings in 18 prospectively studied cases that had substantial pathology-defined cerebrovascular disease (CVD) at autopsy. Nine cases had minimal AD pathology, while the remainder had moderate or severe degrees of AD pathology. Cognitive status at last evaluation ranged from mild cognitive impairment to moderate dementia. Clinical features were quite variable; only 40% of cases with high CVD levels had elevated Hachinski Ischemia Scale scores and neither abrupt onset nor stepwise progression was found in most high CVD cases, even when AD changes were essentially absent. The presence of dementia was predictably related to the level of neurofibrillary pathology, but was not related to the severity of CVD. Neuropsychologists expert in the evaluation of dementia used a priori criteria to diagnose neuropsychological protocols (blind to all other data) from cases with pathology-informed diagnoses of AD, IVD, and mixed dementia. Sensitivity and specificity were both high for AD, sensitivity for detecting pure IVD was poor, and values were intermediate for detecting IVD irrespective of AD levels. A illustrative case example is included. We conclude that the profile of cognitive impairment in IVD is highly variable, but that in clinical settings neuropsychological readings may contribute to the differential diagnosis of dementia.

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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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PubMed2002

Imaging Interactions between Alzheimer's disease and cerebrovascular disease.

There is a growing body of evidence suggesting that Alzheimer's disease (AD) and cerebrovascular disease (CVD), two common disorders of aging, are related in ways that extend beyond their coincident co-occurrence. Thus, there is a need to understand how the two pathological processes interact to contribute to dementia. In this article, we review two recent studies from our laboratory that use MRI and PET to begin to reveal the nature and mechanisms of the relationship between AD, CVD, and dementia.

Alzheimer Disease↗

PubMedDate not supplied

MCI is associated with deficits in everyday functioning.

The purpose of the present study was to examine the types of impairments in everyday function that accompany mild cognitive impairment (MCI). Data for this study was collected from 434 individuals consecutively evaluated at a university-based Alzheimer's Center. A total of 96 participants were diagnosed with MCI, 105 were cognitively normal, and 233 had dementia. Informant ratings of participants' abilities were obtained across different functional domains reflecting everyday abilities related to memory, language, visual spatial abilities, planning, organization, and divided attention. As expected, the demented group was significantly more impaired than the healthy control and MCI groups across all of the functional domains. The MCI group also showed significantly more functional impairment relative to healthy controls in all of the functional domains. Examination of the effect sizes as a measure of the magnitude of functional impairment in the MCI groups relative to controls showed that the greatest degree of impairment occurred within the Everyday Memory domain. The current findings suggest that individuals with MCI demonstrate deficits in a wide range of everyday functions but that the magnitude of these changes is greatest for those functional abilities that rely heavily on memory.

Activities of Daily Living↗