Alzheimer Disease: Royall DR

Royall DR. · Division of Aging and Geriatric Psychiatry, The University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, Mail Code 7792, United States. · Neurobiol Aging. · Pubmed #17055613 No free full text.

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Royall DR. · No affiliation provided · J Am Geriatr Soc. · Pubmed #15209665 No free full text.

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Royall DR. · Department of Psychiatry, South Texas Veterans Health System Audie L. Murphy Division, Geriatric Research Education and Clinical Center, San Antonio, TX, USA. · Cleve Clin J Med. · Pubmed #18540156 links to  free full text

Abstract: Right hemisphere dysfunction is associated with mortality in Alzheimer's disease (AD) and other neurologic conditions. These associations may be mediated by insular pathology, as insular lesions result in demonstrable changes in cardiovascular and autonomic control. AD affects the insulae at a preclinical stage, and insular AD pathology may be present in up to 40% of nondemented septuagenarians and octogenarians. This pathology can affect in vivo cardiac conduction and thereby dispose to cardiac arrhythmias and sudden death. Thus, AD pathology should be considered as a possible explanation for autonomic morbidity and mortality in nondemented elderly persons.

Román GC, Sachdev P, Royall DR, Bullock RA, Orgogozo JM, López-Pousa S, Arizaga R, Wallin A. · Department of Medicine/Neurology, University of Texas HSC at San Antonio and the Audie Murphy Veterans Administration Hospital, Mail Code 7883, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. · J Neurol Sci. · Pubmed #15537526 No free full text.

Abstract: 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.

Román GC, Royall DR. · University of Texas Health Science Center at San Antonio and the Audie L Murphy Veterans Hospital, San Antonio, Texas, USA. · Lancet Neurol. · Pubmed #14980525 No free full text.

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Royall DR, Lauterbach EC, Cummings JL, Reeve A, Rummans TA, Kaufer DI, LaFrance WC, Coffey CE. · The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #12426407 links to  free full text

Abstract: This report reviews the state of the literature and opportunities for research related to "executive control function" (ECF). ECF has recently been separated from the specific cognitive domains (memory, language, and praxis) traditionally used to assess patients. ECF impairment has been associated with lesions to the frontal cortex and its basal ganglia-thalamic connections. No single putative ECF measure can yet serve as a "gold standard." This and other obstacles to assessment of ECF are reviewed. ECF impairment and related frontal system lesions and metabolic disturbances have been detected in many psychiatric and medical disorders and are strongly associated with functional outcomes, disability, and specific problem behaviors. The prevalence and severity of ECF deficits in many disorders remain to be determined, and treatment has been attempted in only a few disorders. Much more research in these areas is necessary.

Román GC, Royall DR. · Department of Medicine, University of Texas Health Science Center at San Antonio, Audie L. Murphy Memorial Veterans Hospital, 78284-7883, USA. · Alzheimer Dis Assoc Disord. · Pubmed #10609685 No free full text.

Abstract: Problems with diagnostic criteria for vascular dementia (VaD) stem from the inadequacy of the current dementia concept, a paradigm based on amnestic and other cortical deficits typical of Alzheimer disease (AD). However, most cases of VaD are due to subcortical lesions such as Binswanger-type periventricular white matter ischemia, or strokes causing decreased frontal activation and diaschisis-mediated cerebral hypoperfusion. We propose a new definition of dementia based on executive dysfunction and a formal assessment of executive control functions (ECF) for the diagnosis of VaD. The instruments proposed are the rapid screening executive clock-drawing task (CLOX; Royall et al. J Neurol Neurosurg Psychiatry 1998;64:588-94), and the more comprehensive Executive Interview Test (EXIT25; Royall et al. J Am Geriatr Soc 1992;40:122-6). Extensive application of these tests in elderly subjects in retirement communities has shown that both are brief, simple to administer, and more sensitive case-finding tools for cognitively impaired individuals than the Mini-Mental State Examination (MMSE). These three tests (CLOX, EXIT25, MMSE) accurately separate nondemented subjects from those with cortical or subcortical (frontal system) dementias. In addition, for controlled clinical trials of VaD, formal evaluation of motor and frontal sphincter functions--usually not considered part of the dementia syndrome--should also be included. Evaluation of gait and falls, timed-walk, manual dexterity, timed finger-tapping, and frontal bladder control (urge incontinence and nocturia) should improve determination of functional status and disability, and more accurately measure the effects of potential therapies.

Royall DR, Chiodo LK, Mouton C, Polk MJ. · Department of Psychiatry, South Texas Veterans' Health System Audie L. Murphy Division GRECC and the University of Texas Health Science Center, San Antonio, TX 78284-7792, USA. · Am J Geriatr Psychiatry. · Pubmed #17322135 No free full text.

Abstract: OBJECTIVE: The objective of this longitudinal cohort study was to study the cognitive domains associated with five-year longitudinal survival among healthy, well-educated, noninstitutionalized elderly. METHODS: Survival curves were generated as a function of cross-sectional baseline cognitive test performance. RESULTS: Nonverbal tests were significantly associated with survival. This finding was markedly consistent. Several nonverbal tasks were each significantly associated with survival independently of age, gender, baseline level of care, and healthcare utilization. In a multivariate model, copying a clock made the strongest, independent contribution to survival. CONCLUSIONS: Right hemisphere integrity in general and nonverbal drawing tasks in particular have been associated with survival in conditions as diverse as Alzheimer disease, stroke, and epilepsy. This study extends this association to "normal" aging. The mechanism by which nonverbal cognitive function is related to mortality remains unclear but may be mediated by changes in right hemisphere cortical control of autonomic function. Nondemented older persons may be at risk. Clock drawing may provide a simple means of identifying them.

Royall DR, Gao JH, Kellogg DL. · Department of Psychiatry, South Texas Veterans' Health System Audie L. Murphy Division GRECC and the University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78284-7792, United · Med Hypotheses. · Pubmed #16806725 No free full text.

Abstract: 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.

Royall DR, Chiodo LK, Polk MJ. · Department of Psychiatry, South Texas Veterans' Health System Audie L. Murphy Division GRECC and University of Texas Health Science Center, San Antonio, TX 78284, USA. · Neuroepidemiology. · Pubmed #15272221 No free full text.

Abstract: We estimated the relative frequency of isolated memory impairment versus isolated and comorbid impairment in executive control function (ECF). One hundred and ninety-three noninstitutionalized residents of a single Comprehensive Care Retirement Community (mean age 79.2 years) were investigated. The subjects were tested with multiple measures of memory and ECF. Test scores were standardized to minimize scaling effects. 'Impairment' was defined as performance < or =1.5 standard deviations below the mean for the entire sample (i.e., a z score < or =-1.5). Disability was estimated as the sum of self-reported activities of daily living and instrumental activities of daily living. The cognitive test performance was significantly associated with functional impairment, independently of age. ECF and memory measures were significantly intercorrelated. Both were significantly and independently associated with disability ratings. 6-10% of the subjects had memory impairment; 25-35% of the memory-impaired subjects had comorbid ECF impairments. An additional 4-7% of the subjects had isolated ECF impairment. A significant fraction of the cases otherwise meeting the criteria for 'mild cognitive impairment' may have comorbid ECF impairment. This raises the issue of whether they might be more properly classified as 'demented'. In addition, isolated ECF impairment may affect almost as many persons as isolated memory impairment. Isolated ECF impairment is not consistent with the natural history of preclinical Alzheimer's disease, suggests other conditions, and can be disabling, independently of age and/or memory loss.

Royall DR. · No affiliation provided · J Am Geriatr Soc. · Pubmed #15086675 No free full text.

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Royall DR, Palmer R, Chiodo LK, Polk MJ. · Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas 78284-7792, USA. · Exp Aging Res. · Pubmed #12959874 No free full text.

Abstract: The authors studied longitudinal change in learning efficiency as a predictor of future dementia type among healthy, well-educated, noninstitutionalized elderly retirees. Serial assessments of memory were obtained using the California Verbal Learning Test (CVLT). Latent growth (LG) models were developed from the slopes of the subjects' performance over the first five CVLT learning trials at each of three serial administrations (e.g., cohort inception [i.e., baseline] [CVLT1], 18 months [CVLT2] and 36 months [CVLT3]). The resulting growth curves were incorporated into a higher order LG model representing the dynamic change in learning efficiency over time (DeltaCVLT). DeltaCVLT was used to predict each subject's "dementia type" (i.e., clinical state) at 36 months (e.g., no dementia, Type 1 [Alzheimer type] dementia or Type 2 [non-Alzheimer type] dementia), after adjusting for CVLT1, baseline age, and baseline dementia type. Nonlinear (logarithmic) LG models of CVLT1-CVLT3 and DeltaCVLT best fit the data. There was significant variability about both CVLT1 and DeltaCVLT, suggesting subgroups in the sample with significantly different baseline memory function, and different rates of deterioration in learning efficiency. Age, baseline dementia type, and DeltaCVLT made significant independent contributions to final dementia type. CVLT1 did not predict final dementia type independently of the other covariates. These data suggest that baseline memory performance in noninstitutionalized elderly retirees does not predict future dementia type independently of the dynamic rate of change in memory measures. Serial administrations of memory tests may help identify nondemented persons at greater or lesser risk for conversion to frank dementia in the near-term.

Royall DR, Palmer R, Mulroy AR, Polk MJ, Román GC, David JP, Delacourte A. · Departments of Psychiatry, Medicine, and Pharmacology, South Texas Veterans' Health System, Audie L. Murphy Division GRECC, University of Texas Health Science Center, San Antonio, Texas, USA. · Exp Aging Res. · Pubmed #11928525 No free full text.

Abstract: The authors developed multivariate models to examine the association between Clinical Dementia Rating (CDR) scale scores and the spatial distribution of paired helical filament tau (PHF-tau) pathology. Severity of tauopathy was examined in 14 cortical regions of interest (ROIs). Classification trees were used to test the independent hierarchical contributions of each ROI to dementia. Multiple-regression and cluster analyses were performed to determine the relative contributions of select ROIs to dementia. Dementia (CDR > or = 1) was modeled as a dichotomous variable. Autopsy material was obtained from 124 demented and nondemented elderly patients. All ROIs except the hippocampus made significant contributions to dementia. However, they were not independent. In multivariate models, only a single step (Step 7 in a hierarchical progression), which contained four ROIs, contributed significantly to dementia. A classification tree resulted in a single decision split, suggesting that only Step 7 ROIs need be considered. A total of 89.4% of the cases were correctly classified (p < .0001). Twelve discrepant cases all had superimposed vasculopathy that might also have affected the function of Step 7 ROIs. The transition to clinical dementia was associated with the presence of tauopathy in A9/10, A22, A23, and A39. Animal studies suggest that these represent a single distributed cortical network focusing on prefrontal regions that provide "executive control" over complex goal-directed behaviors. A22, A23, and A39 provide major afferents to other frontal systems and have previously been implicated in very early clinical Alzheimer's disease.

Royall DR, Chiodo LK, Polk MS, Jaramillo CJ. · Department of Psychiatry, The Audie L. Murphy VA Geriatric Research Education Clinical Center and University of Texas Health Science Center at San Antonio, Tex., 78229-3900, USA. · Neuroepidemiology. · Pubmed #11901275 No free full text.

Abstract: OBJECTIVES: To determine whether or not (1) impaired olfactory function is associated with impaired memory on neuropsychological testing in healthy retirees, and if so then (2) whether memory impairment is most consistent with a mesiotemporal rather than frontal system disorder. METHODS: 173 independent residents of a continuing care retirement community were studied. Subjects completed the University of Pennsylvania Smell Identification Test (UPSIT) and a battery of both general and specific cognitive measures that included the Mini-Mental State Examination (MMSE) and the Executive Interview (EXIT25). Subjects were examined twice over 3 years. RESULTS: UPSIT performance was normal in 21% and in the 'anosmic' range in 25% of subjects. Anosmic UPSIT performance was associated with significantly worse performance on all cognitive tests. However, only short-term verbal memory was independently associated with UPSIT-defined anosmia. This association remained significant after adjusting for the other cognitive and sociodemographic variables. The memory deficits of anosmic subjects were qualitatively consistent with a cortical type (type 1) dementing illness such as Alzheimer's disease (AD). Over time, UPSIT-defined 'anosmic' cases suffered significantly greater declines on both the MMSE and the EXIT25, independently of baseline age, gender and MMSE score. CONCLUSIONS: Impaired odor identification in individuals without overt dementia is associated with an AD-like memory impairment and an increased rate of cognitive decline. The comorbid association of these deficits is consistent with the known hierarchical spread of preclinical AD pathology and may be a specific indicator of future clinical AD dementia.

Royall DR, Mulroy AR, Chiodo LK, Polk MJ. · Department of Psychiatry, South Texas Veterans' Health System Audie L. Murphy Division GRECC, San Antonio, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #10542825 No free full text.

Abstract: We examined six clock-drawing task (CDT) scoring systems relative to the Executive Interview (EXIT25, a measure of Executive Control Function [ECF]) and the Mini-Mental State Exam (MMSE). Subjects included n = 33 National Institute of Neurological, Communicative Disorders, and Stroke "probable" Alzheimer's disease (AD) cases and n = 52 independent living controls. AD cases and controls differed on the EXIT25, MMSE, and all CDTs. All CDTs were significantly correlated with the EXIT25 (ranging from r = .56 to r = .78). These associations generally persisted after adjusting for Age, Education, and MMSE scores. In backwards stepwise linear multivariate regression models, only CLOX: An Executive Clock-Drawing Task scores contribute significantly to EXIT25 scores (R2 = .68) and MMSE scores (R2 = .72). Clock drawing draws upon both executive and general cognitive resources. CLOX explains incrementally more variance in ECF than other CDTs.

Royall DR. · No affiliation provided · J Am Geriatr Soc. · Pubmed #15209669 No free full text.

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Royall DR. · No affiliation provided · Psychol Med. · Pubmed #15099434 No free full text.

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Royall DR, Román GC, Delacourte A. · No affiliation provided · Exp Aging Res. · Pubmed #12735084 No free full text.

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Royall DR. · No affiliation provided · Stroke. · Pubmed #12215573 links to  free full text

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Royall DR, Espino DV. · No affiliation provided · J Am Geriatr Soc. · Pubmed #12110087 No free full text.

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Royall DR, Roman GC. · No affiliation provided · Neurology. · Pubmed #10953213 No free full text.

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Royall DR, Román GC. · No affiliation provided · Rev Neurol. · Pubmed #10652771 No free full text.

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