Alzheimer Disease: Doody RS

Pavlik VN, Doody RS, Massman PJ, Chan W. · Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX 77098-3926, USA. · Dement Geriatr Cogn Disord. · Pubmed #16954693 No free full text.

Abstract: BACKGROUND: Lower education is associated with a higher risk of developing Alzheimer's disease (AD). Years of education and measures of general intellectual function (IQ) are highly correlated. It is important to determine whether there is a relationship between education and AD outcomes that is independent of IQ. OBJECTIVE: To test the hypothesis that premorbid IQ is a stronger predictor of cognitive decline, global progression, and overall survival, than education in patients with AD. METHODS: The study included 478 probable AD patients (322 women and 156 men, mean age 74.5 years) followed in a large AD referral center for a mean of 3.2 years. Eligible participants had a baseline estimate of premorbid IQ using the American version of the Nelson Adult Reading Test (AMNART) and at least one follow-up visit with complete neuropsychological assessment. We used random effects linear regression analysis, and Cox proportional hazards analysis to determine whether or not education and/or premorbid IQ were independently associated with cognitive decline, global progression of AD, and survival. RESULTS: When the baseline AMNART score was included in regression models along with education and other demographic variables, AMNART score, but not education, was associated with a higher baseline score and slower rate of decline in MMSE and ADAS-Cog scores, and the Clinical Dementia Rating sum of boxes score. Neither higher premorbid IQ nor higher education was associated with longer survival. CONCLUSIONS: We conclude that a baseline AMNART score is a better predictor of cognitive change in AD than education, but neither variable is associated with survival after diagnosis.

Waring SC, Doody RS, Pavlik VN, Massman PJ, Chan W. · Division of Epidemiology, University of Texas School of Public Health, Houston, TX 77030, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16327343 No free full text.

Abstract: Survival among patients with dementia is critical information needed for planning and assessing the overall impact of dementia. Attrition from longitudinal cohorts often limits the confidence in survival estimates. For this study, we examined survival among dementia patients from a large multi-ethnic population with excellent longitudinal follow-up. Subjects were all Baylor Alzheimer's Disease Center patients residing in the greater Houston area at the time of initial diagnosis. Vital status was available for all subjects. We estimated median survival time (Kaplan-Meier) from first symptom onset and from diagnosis, and examined the effects of baseline patient characteristics on survival. Median survival time for patients with any form of dementia was 10.5 years from onset and 5.7 years from diagnosis. Similarly, median survival time for probable Alzheimer disease patients was 11.3 years from onset and 5.7 years from diagnosis. Significant trends of decreasing survival with increasing age group (<70; 70-79, > or = 80) were evident for all dementia patients and for patients with Alzheimer disease. Our findings are consistent with previous studies and provide compelling evidence that survival from onset or diagnosis of dementia depends more on age than any other factor.

Hoyt BD, Massman PJ, Schatschneider C, Cooke N, Doody RS. · Department of Psychology, University of Houston, Houston, Tex, USA. · Arch Neurol. · Pubmed #15767511 links to  free full text

Abstract: BACKGROUND: The apolipoprotein E epsilon4 (APOE epsilon4) allele is associated with an increased risk of developing Alzheimer disease (AD). However, findings regarding an association between the APOE epsilon4 allele and the rate of decline in AD have been mixed. OBJECTIVE: To examine the relationship between the APOE epsilon4 allele and the rate of cognitive and functional decline in AD using individual growth curve analyses. DESIGN: Longitudinal cohort study. SETTING: Alzheimer Disease Research Center at Baylor College of Medicine. PATIENTS: A total of 189 patients meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria for probable AD at baseline who underwent annual follow-up evaluations for at least 2 years. MAIN OUTCOME MEASURES: Individual growth curve parameters derived from baseline and follow-up performance on global and specific measures of cognitive and functional abilities. RESULTS: Patients with 2 APOE epsilon4 alleles exhibited a slower rate of decline on measures of global cognitive functioning and functional abilities. No significant association was detected between the APOE epsilon4 allele and the rate of decline on measures of specific cognitive functions. CONCLUSIONS: Although the APOE epsilon4 allele is associated with an increased risk of developing AD, it seems that having 2 APOE epsilon4 alleles is associated with a slower clinical course. These findings are consistent with hypotheses that the biological processes contributing to the onset of AD are different from those involved in determining its clinical course.

Clark CM, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, Morris JC, McKeel DW, Farlow M, Weitlauf SL, Quinn J, Kaye J, Knopman D, Arai H, Doody RS, DeCarli C, Leight S, Lee VM, Trojanowski JQ. · Departments of Neurology, Center for Neuerodegenerative Disease Research, alzheimer's Disease Center, Philadelphia, PA 19104, USA. · Arch Neurol. · Pubmed #14676043 links to  free full text

Abstract: BACKGROUND: Tau and beta-amyloid (Abeta) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific pathology, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. OBJECTIVES: To correlate antemortem cerebrospinal fluid (CSF) tau and Abeta levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Abeta. DESIGN: Prospective study. SETTING: Ten clinics experienced in the diagnosis of neurodegenerative dementias.Patients One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. MAIN OUTCOME MEASURES: Correlation of CSF tau and Abeta with final diagnosis. RESULTS: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Abeta42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). CONCLUSIONS: Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean +/- 2 SDs of the cognitively normal cohort.

Davis RN, Massman PJ, Doody RS. · Department of Psychology, University of Houston, Houston, TX 77204-5022, USA. · Arch Clin Neuropsychol. · Pubmed #14591475 No free full text.

Abstract: Blood pressure is often lower among patients with Alzheimer's disease (AD) compared to nondemented older adults. Lower blood pressure in AD correlates with reduced cerebral blood flow and cortical atrophy, but its effect on neuropsychological functioning is unclear. We assessed the effects of blood pressure on tests of dementia severity, attention, memory, language, verbal and nonverbal reasoning, motor/psychomotor functioning, and activities of daily living (ADL) among probable AD patients (n=609). As hypothesized, lower systolic blood pressure (SBP) predicted reduced attention (Digits Forward and Backward), memory (Visual Reproduction I), and ADLs. Unexpectedly, lower pulse pressure (SBP-DBP) predicted greater dementia severity (Mini-Mental State Examination, MMSE), attention (Digits Forward and Backward), memory (Logical Memory I and Visual Reproduction I), and ADLs. These findings may reflect a tendency for less severely demented patients to exhibit normal age-related changes in blood pressure, whereas abnormal patterns may develop with increased dementia severity.

Doody RS, Dunn JK, Huang E, Azher S, Kataki M. · Department of Neurology and Alzheimer's Disease Center, Baylor College of Medicine, Houston, TX 77030, USA. · Dement Geriatr Cogn Disord. · Pubmed #14560058 No free full text.

Abstract: BACKGROUND: We developed a set of questions for generating an estimate regarding the date of first symptoms to the nearest half-year. Physicians then revised this estimate in conjunction with medical record review and patient/informant interviews, and by testing the estimate by recall of life events. One experienced examiner rated 36 patients, and each was independently rated by a second, less experienced rater. The physician ratings were compared to each other and to an unstructured caregiver estimate of duration using Lin concordance coefficients. There was excellent agreement between independent physician raters (rho = 0.95, p < 0.001). Caregiver estimates of duration were usually shorter because of failure to relate the first symptoms to the onset of disease.

Weiner MF, Doody RS, Sairam R, Foster B, Liao TY. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA. · Dement Geriatr Cogn Disord. · Pubmed #11731709 No free full text.

Abstract: BACKGROUND: Reports on the frequency of major depression in Alzheimer's disease are conflicting, some suggesting that it is frequent, others suggesting that it is uncommon. METHODS: We examined the prevalence and incidence of symptom clusters meeting criteria for major depressive disorder (MDD) in two large series of cases diagnosed prospectively by NINCDS/ADRDA criteria as probable or possible Alzheimer's disease. Standard DSM-III-R criteria were employed at one site, the CERAD modification of DSM-III-R criteria at the other. Both sites required the presence of depressed mood on direct patient examination at the time of initial evaluation in order to meet criteria for MDD. RESULTS: At the center using standard DSM-III-R criteria (n = 329), there was a 0.9% prevalence of symptom clusters meeting criteria for MDD. At the center using the CERAD modification (n = 586), MDD prevalence was 4.8%. Incidence rates at both centers were below 2% per year over 3 years. CONCLUSIONS: We concluded that DSM-III-R MDD is not common in AD patients.

Doody RS, Azher SN, Haykal HA, Dunn JK, Liao T, Schneider L. · Department of Neurology and Alzheimer's Disease Research Center, Baylor College of Medicine, 6550 Fannin Suite, 1801 Houston, TX 77030, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #11032626 links to  free full text

Abstract: OBJECTIVE: To assess the relation between APO E genotype and MRI white matter changes in Alzheimer's disease. The APO epsilon4 allele is correlated with amyloid angiopathy and other neuropathologies in Alzheimer's disease and could be associated with white matter changes. If so, there should be a dose effect. METHODS: 104 patients with probable Alzheimer's disease (NINCDS-ADRDA criteria) in this Alzheimer's Disease Research Centre were studied. Patients received MRI and APO E genotyping by standardised protocols. Axial MRI was scored (modified Schelten's scale) for the presence and degree of white matter changes and atrophy in several regions by a neuroradiologist blinded to genotype. Total white matter and total atrophy scores were also generated. Data analysis included Pearson's correlation for regional and total imaging scores and analysis of variance (ANOVA) (or Kruskal-Wallis) and chi(2) for demographic and disease related variables. RESULTS: 30 patients had no epsilon4, 53 patients were heterozygous, and 21 patients were homozygous. The three groups did not differ in sex distribution, age of onset, age at MRI, MMSE, clinical dementia rating, or modified Hachinski ischaemia scores. There were no significant correlations between total or regional white matter scores and APO E genotype (Pearson correlation). CONCLUSIONS: No correlation between total or regional white matter scores and APO E genotype was found. The pathogenesis of white matter changes in Alzheimer's disease may be independent of APO E genotype.

Doody RS. · Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. · Brain Cogn. · Pubmed #10739589 No free full text.

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Doody RS, Vacca JL, Massman PJ, Liao TY. · Department of Neurology and Alzheimer's disease Research Center, Baylor College of Medicine, Houston, Tex 77030, USA. · Arch Neurol. · Pubmed #10488815 links to  free full text

Abstract: BACKGROUND: Research on the influence of handedness on the clinical presentation and neuropsychology of Alzheimer disease (AD) is scarce. OBJECTIVE: To compare clinical presentation and neuropsychological test performance of right- and left-handed patients with AD. DESIGN: We hypothesized that left-handedness would be associated with younger onset, more rapid progression, and possibly cognitive hemispheric asymmetry. After determining handedness with the Edinburgh Inventory for Handedness for 922 patients with AD, 18 left-handed patients were compared with 18 right-handed patients matched individually on Mini-Mental State Examination scores, education, and age. We compared clinical characteristics (eg, age of onset), estimated rate of initial cognitive decline, language and visuospatial test performances, and patterns of cognitive and motor asymmetries for the 2 groups. SETTING: Alzheimer's Disease Research Center at Baylor College of Medicine, Houston, Tex. MAIN OUTCOME MEASURES: Results of the Wechsler Adult Intelligence Scale-Revised verbal and performance IQ tests, the Western Aphasia Battery sequential commands subtest, the Boston Naming Test, the Halstead-Reitan Finger-Tapping Test, and the calculated Rate of Initial Progression. RESULTS: We found that left-handed patients had younger ages of onset but unexpectedly lower estimated rates of initial cognitive decline, and their results on language tests did not differ from those of right-handed patients. Regarding asymmetry, left-handed patients were more likely than right-handers to obtain lower verbal IQ than performance IQ scores and to exhibit faster finger-tapping speeds with their nondominant hand, but group differences did not attain statistical significance. There were disproportionately few left-handed patients with AD compared with population norms. CONCLUSIONS: Left-handed patients with AD do not differ from right-handed patients in the severity or pattern of neuropsychological deficits. Left-handedness or some factor associated with it may contribute to the early appearance of cognitive deficits during the development of Alzheimer disease, but may temper the subsequent rate of progression of deficits.

Doody RS, Strehlow SL, Massman PJ, Feher EP, Clark C, Roy JR. · Baylor College of Medicine, Department of Neurology and Alzheimer's Disease Research Center, Houston, Texas 77030, USA. · Alzheimer Dis Assoc Disord. · Pubmed #10192643 No free full text.

Abstract: There is no brief patient-derived rating scale for staging and following profoundly demented Alzheimer disease (AD) patients. We developed the Baylor Profound Mental Status Examination (BPMSE) modeled after the Mini-Mental State Examination (MMSE) to meet this need. The BPMSE consists of 25 cognitive questions that assess orientation, language, attention, and motor functioning; 10 examiner ratings of presence or absence of problem behaviors; and 2 qualitative observations of language and social interaction. Two hundred eight probable or possible AD patients (MMSE scores of 20 or less) received the BPMSE. Some were also rated on the clinical dementia rating (CDR) and Lawton activities of daily living (ADL). A ceiling effect occurred at MMSE scores above 11. BPMSE cognitive scores and MMSE scores correlated significantly (r = 0.76, p < 0.0001). Subareas of the BPMSE also intercorrelated significantly. The BPMSE correlated with both CDR and ADL scores (p < 0.001). Internal consistency, interrater reliability, and test-retest stability were excellent. There was no floor effect, and BPMSE scores continued to decline after the MMSE reached 0. The BPMSE is a quick and easy staging tool with excellent validity and test-retest stability that measures cognitive function successfully in patients with MMSE scores below 12. The scale is sensitive to longitudinal change and continues to assess decline when performance has reached the lowest levels on conventional measures.