Biomedical subjects
Donald R Royall
Publications and source records attributed to Donald R Royall.
Insular Alzheimer's disease pathology as a cause of "age-related" autonomic dysfunction and mortality in the non-demented elderly.
Only a few brain structures have been implicated in the autonomic control of blood pressure and heart rate. Among them are heteromodal association areas in the cortex, especially the insular cortex. Ischemic insular lesions have been associated with both cardiac arrhythmias and mortality. However, stroke may not be the only insular pathology with the potential to disrupt autonomic function. Alzheimer's disease (AD) is associated with both insular pathology and autonomic dysfunction. Alzheimer's dementia is merely the final stage of a pathological process that spans decades. Recent studies have demonstrated a hierarchichal sequence of AD pathology that includes the insular cortex. This may explain why AD has effects on BP and central autonomic cardio-regulatory functions. However, AD reaches the insular cortex at a "preclinical" stage in its development (i.e., before "dementia" can be diagnosed). Thus, AD pathology should also be considered as a possible explanation for autonomic morbidity and mortality in non-demented elderly persons. We hypothesize that autonomic dyscontrol, commonly seen in non-demented well elderly persons without significant cardiovascular disease (CVD), reflects subclinical stages of AD pathology affecting the insular cortex. If true, then preclinical AD pathology should be considered as a possible explanation for arrhythmia/fall related morbidity and mortality in non-demented elderly persons.
Mild cognitive impairment and functional status.
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Mexican-American ethnicity and cognitive function: findings from an elderly southwestern sample.
Relatively little is known about late-life patterns of cognitive function among Hispanics of Mexican heritage who reside in the United States. The authors designed a study to assess the association between Mexican-American ethnicity (defined in terms of childhood and adolescent developmental history) and cognitive function among elderly Mexican-American and non-Hispanic white residents of El Paso County, Texas. Our findings indicate significant associations between the degree of Mexican-American ethnicity and cognitive impairment on all three measures of cognitive function. These statistically significant findings remain after effects of education, age, and gender have been removed from the multiple regression equation. The authors conclude that a dependable and clinically meaningful negative association exists between Mexican-American ethnicity and late-life cognitive function in this region that is mediated by as yet unmeasured variables.
Normal rates of cognitive change in successful aging: the freedom house study.
We determined the rates of cognitive change associated with twenty individual measures. Participants included 547 noninstitutionalized septuagenarians and octogenarian residents of a comprehensive care retirement community who were studied over three years. Latent growth curves (LGC) of multiple cognitive measures were compared to a LGC model of the rates of change in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). All curves were standardized relative to each variable's baseline distribution. Baseline scores were within their expected normal age-specific ranges. Most measures showed significant rates of change over time. There was also significant variability about those rates, suggesting clinical heterogeneity. Many deteriorated over time, as did ADLs and IADLs. However, performance on some measures improved, consistent with learning effects. The rates of change in two measures, the Executive Interview and the Trail Making Test, were closely related to decline in IADLs. These results suggest that age-related cognitive decline is a dynamic longitudinal process affecting multiple cognitive domains. Heterogeneity in the rates of cognitive change may reflect the summed effects of age and comorbid conditions affecting cognition. Some measures may be ill-suited for measuring age-related changes in cognition, either because they are insensitive to change, or hindered by learning effects. Nonverbal measures appear to be particularly well suited for the prediction of age-related functional decline. These observations are relevant to the definition and diagnosis of "dementing" conditions.
An empiric approach to level of care determinations: the importance of executive measures.
BACKGROUND: The ability to predict the level of care received by elderly retirees was compared in a discriminant model and using a classification tree derived from cognitive and noncognitive variables. Methods. Participants were 193 residents (mean age, 79.1+/-5.1 years) of a single, 1,500-bed, continuing care retirement community. They were given a battery of cognitive measures that included tests of general cognition, memory, and executive control function. A multivariate discriminant model of level of care was compared with a classification tree. RESULTS: Residents in congregate high-rises (n=115) differed significantly from those in apartment settings (n=78) with respect to age, Executive Interview (EXIT 25), and the Executive Clock-Drawing Task (CLOX). Only age and executive control function measures (CLOX1, EXIT 25, and Trail Making Test Part B [Trails B]) contributed independently to a discriminant model of level of care (Wilke's lambda=0.92; F [df 4,170]=3.48; p <.01). Sixty-three percent of participants were correctly classified. A classification tree derived from the same variable set was more accurate (75% correctly classified). Age, CLOX1, and EXIT 25 made the most important contributions to the model. The EXIT 25 and CLOX1 thresholds empirically derived from this model coincide with the fifth percentiles for these instruments in a young adult sample. CONCLUSIONS: Executive control function appears to be most responsible for the effect of cognition on level of care. Young adult norms may be most relevant when the effects of cognitive impairment on functional status are assessed.
Executive control mediates memory's association with change in instrumental activities of daily living: the Freedom House Study.
OBJECTIVES: To assess the relative independent contribution of changes in executive control function (ECF) and memory to changes in functional status. DESIGN: Three-year longitudinal cohort study. SETTING: A comprehensive care retirement community. PARTICIPANTS: Five hundred forty-seven noninstitutionalized people aged 70 and older. MEASUREMENTS: The California Verbal Learning Test (CVLT) and Executive Interview (EXIT25). Functional status was assessed using instrumental activities of daily living (IADLs). Latent growth curves of CVLT, EXIT25, and IADLs were modeled. The rate of change in IADLs (adjusted for baseline IADLs and cognition) was regressed on the rate of change in each cognitive measure. Models were also adjusted for baseline age, level of care, and comorbid illnesses. RESULTS: There was significant variability around the baseline means and slopes for all variables. The rate of change in EXIT25 was independently correlated with the rate of change in IADLs (correlation coefficient (r)=-0.52, P<.001). This remained significant after adjusting for baseline EXIT25 scores, IADLs, age, comorbid disease, and level of care. The EXIT25's effect on the rate of change in IADLs was stronger than those of age, baseline IADLs, comorbid disease, or level of care. The rate of change in CVLT scores was not significantly associated with the rate of change in IADLs. CONCLUSION: ECF is a strong, significant, and independent correlate of functional status in normal aging. In contrast, decline in memory, as measured using the CVLT, has no independent association with the rate of change in functional status. This suggests that amnestic mild cognitive impairment can be associated with dementia only though the subsequent or comorbid development of ECF impairment.
The emperor has no clothes: dementia treatment on the eve of the aging era.
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Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia.
Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions. Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.
Executive control and the validity of survey data.
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Prevalence and patterns of executive impairment in community dwelling Mexican Americans: results from the Hispanic EPESE Study.
INTRODUCTION: Little is known about the prevalence of impaired executive control function (ECF) in community dwelling elderly or minority populations. We have determined the prevalence of cognitive impairment and impaired ECF in a community dwelling Mexican American elderly population, and their associations with functional status. SUBJECTS: Subjects were 1165 Mexican Americans age 65 and over who were administered CLOX as part of the third wave of the Hispanic Established Population for Epidemiological Study (HEPESE) conducted from 1998 to 1999. METHODS: ECF was measured by an executive clock-drawing task (CDT) (i.e. CLOX1). Non-executive cognitive function was assessed by the Mini-Mental State Examination (MMSE) and a non-executive CDT (CLOX2). CLOX scores were combined to estimate the prevalence of global CLOX failure (i.e. 'Type 1' cognitive impairment) vs isolated CLOX1 failure (i.e. Type 2 cognitive impairment). RESULTS: 59.3% of subjects failed CLOX1. 31.1% failed both CLOX1 and CLOX2 (Type 1 cognitive impairment). 33.3% failed CLOX1 only (Type 2 cognitive impairment). 35.6% passed both measures [no cognitive impairment (NCI)]. Many subjects with CLOX1 impairment at Wave 3 had normal MMSE scores. This was more likely to occur in the context of Type 2 cognitive impairment. Both CLOX defined cognitive impairment groups were associated with functional impairment. CONCLUSIONS: A large percentage of community dwelling Mexican American elderly suffer cognitive impairment that can be demonstrated through a CDT. Isolated executive impairments appear to be most common. The ability of a CDT to demonstrate ECF impairments potentially offers a rapid, culturally unbiased and cost-effective means of assessing this domain. In contrast, the MMSE is relatively insensitive to ECF assessed by CLOX1.
A diagnostic dilemma: is "Alzheimer's dementia" Alzheimer's disease, vascular dementia, or both?
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Re: De Jager, CA, et al. Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer's disease.
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Declining executive control in normal aging predicts change in functional status: the Freedom House Study.
OBJECTIVES: To assess the contribution of executive control function (ECF) to functional status. DESIGN: Three-year longitudinal cohort study. SETTING: A comprehensive-care retirement community. PARTICIPANTS: Five hundred forty-seven noninstitutionalized septuagenarians. MEASUREMENTS: The Mini-Mental State Examination (MMSE) and Executive Interview (EXIT25). Functional status was assessed using instrumental activities of daily living (IADLs). Latent growth curves of MMSE, EXIT25, and IADL were modeled. The rate of change in IADLs (DeltaIADL), adjusted for baseline IADLs and cognition, was regressed on the rate of change in each cognitive measure (adjusted for baseline cognition). Models were also adjusted for baseline age, level of care, and comorbid illnesses. RESULTS: Baseline test scores were within normal ranges, but mean EXIT25 scores reached the impaired range by the second follow-up. There was significant variability around the baseline means and slopes for all variables. The rate of change in EXIT25 was strongly correlated with DeltaIADL (r=-0.57, P<.001). This remained significant after adjusting for baseline EXIT25 scores, IADLs, age, comorbid disease, and level of care. The effect of the EXIT25 on DeltaIADL was stronger than those of age, baseline IADLs, comorbid disease, or level of care. The rate of change in MMSE scores was not significantly associated with DeltaIADL. CONCLUSION: ECF is a significant and independent correlate of functional status in normal aging. Traditional dementia case finding is likely to underestimate cognition-related disability. Neither a normal baseline MMSE score nor stable MMSE scores over time preclude functionally significant changes in ECF.
The "subsyndromal" syndromes of aging.
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Donepezil's effects remain uncertain.
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