Alzheimer Disease: Mortimer JA

Mortimer JA, Petersen RC. · No affiliation provided · Ann Neurol. · Pubmed #19067352 No free full text.

This publication has no abstract.

Jarvik L, LaRue A, Blacker D, Gatz M, Kawas C, McArdle JJ, Morris JC, Mortimer JA, Ringman JM, Ercoli L, Freimer N, Gokhman I, Manly JJ, Plassman BL, Rasgon N, Roberts JS, Sunderland T, Swan GE, Wolf PA, Zonderman AB. · Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA. · Alzheimer Dis Assoc Disord. · Pubmed #18317242 No free full text.

Abstract: Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the state of knowledge with respect to risk and protective factors for AD and recommend a research agenda with special emphasis on AD offspring.

Mortimer JA, Borenstein AR. · Department of Epidemiology and Biostatistics, University of South Florida, 13201 Bruce B. Downs Blvd., Tampa, FL 33612, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16917193 No free full text.

Abstract: This review provides a summary of epidemiologic tools to facilitate understanding of the design and analysis of studies of Alzheimer disease (AD) and related disorders. Proportions, ratios, rates, prevalence, incidence, study designs, bias, confounding, effect modification, odds and risk ratios, statistical power, and confidence intervals are defined and discussed. Descriptive epidemiology is concerned with describing the distribution of disease by person, place, and time. It is useful for hypothesis generation, but not generally for hypothesis testing. Observational analytic epidemiology focuses on identifying putative causes for an illness. Although its primary mission is hypothesis testing, it can lead to new hypotheses as well. Finally, experimental analytic epidemiology or clinical trials can provide rigorous tests of presumed causal associations. The strengths and limitations of various designs as they apply to determining causal associations in studies of AD and dementia are reviewed. Over the past 60 years, the epidemiologic study of dementia has evolved from basic descriptive studies of prevalence and incidence to case-control and cohort studies and finally to the first clinical trials to prevent AD.

Borenstein AR, Copenhaver CI, Mortimer JA. · Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL 33612, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16493239 No free full text.

Abstract: Research findings obtained over the past 20 years suggest that Alzheimer disease (AD) may have its origins in early life. In this review, we consider the evidence for early-life risk factors for this illness. We propose that risk factors that predict neuropathology are largely distinct from those related to the clinical expression of Alzheimer disease. Early-life risk factors for pathology include genes, chromosomal abnormalities, head injury, insulin resistance, and inflammation. With regard to risk factors for clinical expression of Alzheimer disease, six general groups of childhood exposures are reviewed: (1) perinatal conditions, (2) early-life brain development, (3) early-life body growth, (4) early-life socioeconomic conditions, (5) environmental enrichment, and (6) cognitive reserve. The literature reviewed suggests that risk of Alzheimer disease is probably not determined in any single time period but results from the complex interplay between genetic and environmental exposures throughout the life course. Enhancement or preservation of brain or cognitive reserve could delay the onset of Alzheimer disease and in some cases prevent the disease from occurring altogether.

Mortimer JA, Borenstein AR, Gosche KM, Snowdon DA. · Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL 33612-3899, USA. · J Geriatr Psychiatry Neurol. · Pubmed #16306243 links to  free full text

Abstract: Numerous studies show that the pathology of Alzheimer's disease is present decades before a clinical diagnosis of dementia can be made. Given the likelihood that agents will become available that reliably delay onset and/or slow progression of Alzheimer's disease, it will be important to detect preclinical Alzheimer's disease as early as possible for maximal treatment effect. Detection of individuals by sensitive cognitive measures provides one way to identify people who are at high risk of developing clinical Alzheimer's disease. However, it is likely that those with considerable brain or cognitive reserve will be able to mask cognitive deficits until very close to the onset of the dementia, rendering such cognitive measures insensitive. Optimum biomarkers for Alzheimer's disease therefore need to target the severity of underlying brain pathology independently of brain reserve. Findings are presented showing the importance of higher education and larger brain size in masking the underlying disease pathology.

Mortimer JA, Snowdon DA, Markesbery WR. · Department of Epidemiology and Biostatistics, University of South Florida, 13201 Bruce B. Downs Boulevard, MDC-56, Tampa, FL 33612-3805, USA. · Alzheimer Dis Assoc Disord. · Pubmed #19484916 No free full text.

Abstract: The degree to which the association of epsilon4 with dementia is mediated by AD lesions in comparison with vascular lesions is controversial. The present study was undertaken to determine the roles of Alzheimer disease (AD) and vascular pathology in mediating the effect of apolipoprotein E (APOE)-epsilon4 alleles on dementia. Clinicopathologic correlations were studied in 267 Catholic sisters participating in the Nun Study. The extent to which AD and vascular pathologies mediated the effect of APOEepsilon4 on dementia was investigated using multiple logistic regression. Adjusted for age at death and education, possession of 1 or more epsilon4 alleles was an important risk factor for dementia (odds ratio=2.98; 95% confidence interval, 1.62-5.48). This association was lost (odds ratio=1.38; 95% confidence interval, 0.68-2.80) when an index of the severity of AD-related neuropathology was added to the model, but changed little when measures of the severity of vascular pathology were added. The findings suggest that the effect of epsilon4 on dementia is mediated by the severity of AD pathology. Although infarcts and atherosclerosis contribute to the occurrence of dementia, this contribution seems unrelated to APOE genotype.

Mortimer JA, Snowdon DA, Markesbery WR. · Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL 33612-3805, USA. · Alzheimer Dis Assoc Disord. · Pubmed #18580587 No free full text.

Abstract: Studies suggest that individuals who are at increased risk for Alzheimer disease (AD) in late life differ on measures of cognition, linguistic performance, and brain metabolism in earlier adult life compared with those with lower risk of this illness. The present study was undertaken to determine whether smaller head circumference (HC), a predictor of AD in late life, could influence educational attainment earlier in life, specifically among individuals at increased risk for AD. Data from the Nun Study, a longitudinal clinicopathologic study of dementia, were analyzed using logistic regression to assess the association between HC and attainment of less than a bachelor's degree. Modification of this association was studied by comparing those with and without evidence of increased AD risk, including possession of apolipoprotein E (APOE)-epsilon 4 alleles, occurrence of dementia before death, and satisfaction of AD neuropathologic criteria at autopsy. Small HC was associated with lower educational attainment in those carrying an APOE-epsilon 4 allele [odds ratio (OR)=6.27, 1.21 to 32.48], those who became demented (OR=3.23, 1.27 to 8.21), and those who fulfilled AD neuropathologic criteria (OR=5.03, 1.29 to 19.66), but not in those without these characteristics. These findings suggest that small HC limits educational attainment only among individuals who have greater risk of AD owing to their APOE genotype or who are destined to develop this illness later in life.

Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL. · Department of Psychology, University of Southern California, Los Angeles 90089-1061, USA. · Arch Gen Psychiatry. · Pubmed #16461860 links to  free full text

Abstract: CONTEXT: Twin studies using selected samples have shown high heritability for Alzheimer disease (AD). OBJECTIVE: To evaluate genetic and environmental influences on AD in a fully ascertained population of older twins, including like- and unlike-sex pairs. DESIGN: Five-group quantitative genetic model: male monozygotic twins, female monozygotic twins, male dizygotic twins, female dizygotic twins, and unlike-sex twins. SETTING AND PARTICIPANTS: All twins in the Swedish Twin Registry aged 65 years and older. The study included 11,884 twin pairs, among whom were 392 pairs in which 1 or both members had AD. MAIN OUTCOME MEASURES: All individuals were screened for cognitive dysfunction. Suspected cases of dementia and their co-twins received complete clinical diagnostic evaluations for AD. Estimates of heritability, shared environmental influences, and nonshared environmental influences, adjusting for age, were derived from the twin data. RESULTS: Heritability for AD was estimated to be 58% in the full model and 79% in the best-fitting model, with the balance of variation explained by nonshared environmental influences. There were no significant differences between men and women in prevalence or heritability after controlling for age. Within pairs concordant for AD, intrapair difference in age at onset was significantly greater in dizygotic than in monozygotic pairs, suggesting genetic influences on timing of the disease. CONCLUSIONS: In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women. However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset.

Gatz M, Fratiglioni L, Johansson B, Berg S, Mortimer JA, Reynolds CA, Fiske A, Pedersen NL. · Department of Psychology, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089-1061, USA. · Neurobiol Aging. · Pubmed #15653172 No free full text.

Abstract: The purpose of this report is to describe the Study of Dementia in Swedish Twins (known as HARMONY), including procedures for complete ascertainment of all cases of Alzheimer's disease (AD) and other dementias in 14,435 individuals aged 65 and older from the national Swedish twin registry. Telephone cognitive screening identified 11.5% as positive for cognitive dysfunction. Clinical diagnoses were completed for 1557 individuals, including individuals who screened positive, their twin partners, and a sample of normal controls. Estimated prevalence of dementia ranged from 1.4% for age 65-69 to 29.2% for age 90 and older. Concordance rates for Alzheimer's disease were 59% for monozygotic twins, 32% for like-sexed, and 24% for unlike-sexed dizygotic twins. Among monozygotic twins where both twins had Alzheimer's disease, the within pair difference in age of onset ranged from both becoming demented in the same year to 7 years difference in onset.

Borenstein AR, Wu Y, Mortimer JA, Schellenberg GD, McCormick WC, Bowen JD, McCurry S, Larson EB. · Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, 13201 Bruce B. Downs Blvd., Tampa, FL 33612-3805, USA. · Neurobiol Aging. · Pubmed #15639310 No free full text.

Abstract: To investigate developmental and vascular risk factors for Alzheimer's disease (AD), we examined 90 incident cases of probable AD in a cohort of 1859 individuals followed prospectively for six years. The presence of the APOE-epsilon4 allele was the strongest risk factor, and with increasing survival age, the effect of epsilon4 diminished. Among epsilon4 positives, developmental risk factors such as smaller head circumference (< or =54.4 cm) and having more than four children in the household at age 2-3 were independently associated with incident AD (hazard ratio (HR)=2.6 (95% CI 1.04-6.3) and 3.3 (1.2-9.2), respectively). Among epsilon4 negatives, vascular risk factors were related to AD risk (self-reported diagnoses of transient ischemic attack and diabetes (HR=5.1, 95% CI 1.7-15.5; HR 3.3, 95% CI 1.4-8.1)). These findings indicate that clinical AD is a result of early life as well as later life risk factors, and that genetic predisposition to the disease may modify the constellation of predictors.

Mortimer JA, Gosche KM, Riley KP, Markesbery WR, Snowdon DA. · Institute on Aging, University of South Florida, Tampa FL 33612-3805, USA. · Neurology. · Pubmed #14872025 No free full text.

Abstract: OBJECTIVE: To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. METHODS: Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer's Disease Delayed Word Recall Test administered an average of 1 year prior to death. RESULTS: When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. CONCLUSIONS: The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.

Mortimer JA, Snowdon DA, Markesbery WR. · Institute on Aging, University of South Florida, Tampa, FL 33612-3899, USA. · J Clin Exp Neuropsychol. · Pubmed #12815504 No free full text.

Abstract: To examine the prevalence of dementia associated with having a smaller brain, lower education or both of these characteristics, 294 Catholic sisters were assessed annually for dementia. Sixty participants died and their brains were evaluated to determine fulfillment of neuropathological criteria for Alzheimer's disease (AD). Lower educational attainment and the interaction of smaller head circumference with lower education were associated with the presence of dementia, controlling for age and the presence of one or more apolipoprotein E-epsilon 4 alleles. By contrast, neither low educational attainment nor head circumference was significantly associated with fulfillment of neuropathological criteria for AD. Individuals having both low education and small head circumference were four times as likely to be demented as the rest of the sample. The findings suggest that higher education and larger head size, alone or in combination, may reduce the risk of expressing dementia in late life.

Zarow C, Lyness SA, Mortimer JA, Chui HC. · Department of Neurology, University of Southern California, Los Angeles, CA, USA. · Arch Neurol. · Pubmed #12633144 links to  free full text

Abstract: CONTEXT: Alzheimer disease (AD) and Parkinson disease (PD) are associated with neuronal degeneration in major subcortical nuclei, but few studies have examined the neuronal degeneration in these nuclei concurrently. OBJECTIVE: To identify clinical and pathological correlates of neuronal loss in the nucleus basalis (NB), locus coeruleus (LC), and substantia nigra pars compacta (SN) in AD and PD. DESIGN: The study sample comprised 86 cases with pathologically confirmed AD, 19 cases with PD, and 13 healthy elderly control subjects. The number of nucleolated neurons was counted in representative sections of the NB, LC, and SN. Effect sizes (ES) were computed to determine the standardized difference in cell counts relative to healthy controls. RESULTS: Cases of AD showed the greatest neuronal loss in the LC (ES = 3.16) followed by the NB (ES = 1.10), but variable loss in the SN (ES = 0.16). Cases of PD also showed the greatest neuronal loss in the LC (ES = 6.47), followed by the SN (ES = 2.58) and the NB (ES = 0.85). Significant correlations were found between the number of neurons in the NB and LC in PD (r = 0.54, P<.05), as well as AD (r = 0.24, P<.05). The duration of illness correlated with greater neuronal loss in the LC and NB in AD, and greater neuronal loss in the SN in PD. CONCLUSIONS: For both AD and PD the greatest neuronal loss was found in the LC. In AD, neuronal loss was most severe and best correlated with the duration of illness in the LC, rather than in NB as traditionally expected. Correlations between neuronal loss in the LC and NB (but not SN) in both PD and AD suggest that the former 2 nuclei may share common pathogenetic susceptibilities. Given the prominent loss of neurons in the LC, detection and treatment of noradrenergic deficiencies warrant attention in both AD and PD.

Gatz M, Reynolds CA, John R, Johansson B, Mortimer JA, Pedersen NL. · Department of Psychology, University of Southern California, Los Angeles, California 90089-1061, USA. · Int Psychogeriatr. · Pubmed #12475088 No free full text.

Abstract: This study examined the utility of the TELE, a telephone assessment for dementia, in a sample of 269 individuals that was not selected on the basis of previous dementia diagnosis. Thus, the conditions of the study reflect the actual situation in which a screening instrument might be employed. Scores on TELE were compared to dementia diagnoses. Using the best cutoff score, sensitivity was .86 and specificity was .90. Longitudinal follow-up established that false positives primarily included those who subsequently developed dementia. Telephone screening for dementia has both clinical and research applications. One recommendation based on our experience is that longitudinal studies should include a telephone interview component for anyone who drops out of the study, to enable characterizing the cognitive status of dropouts.

Ashford JW, Mortimer JA. · Department of Psychiatry, Sanders-Brown Center on Aging, University of Kentucky, Veterans Affairs Medical Center, Lexington, KY 40536-0230, USA. · J Alzheimers Dis. · Pubmed #12226536 No free full text.

Abstract: This team takes the position that what is commonly referred to as non-familial Alzheimer's disease (AD) is predominantly due to genetic factors. Population-based studies suggest that genetic factors cause the majority of cases that begin after age 60. There are several lines of evidence supporting this position: Data from the Nun Study suggest that the risk for AD is largely established by early adulthood, implying that later adult exposures likely play only a small role in causation. Family studies show that first-degree blood relatives of persons with non-familial AD have a substantially increased risk of AD relative to controls. Twin studies suggest that the heritability of AD exceeds 60%. Environmental factors, such as socioeconomic status, education, and head injury, are strong risk factors for AD only in individuals with a genetic predisposition. The APOE genotype is a powerful risk factor for AD and accounts for as much as 50%. There are numerous other candidate genes with strong associations with AD that presumably explain the remaining population risk. This paper further reviews the mechanisms associated with AD causation for APOE and other candidate genes and implications for the development of prevention strategies.

Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA. · Institute on Aging, University of South Florida, Tampa 33612-3899, USA. · Neurology. · Pubmed #12034782 No free full text.

Abstract: OBJECTIVE: To determine whether hippocampal volume is a sensitive and specific indicator of Alzheimer neuropathology, regardless of the presence or absence of cognitive and memory impairment. METHODS: Postmortem MRI scans were obtained for the first 56 participants of the Nun Study who were scanned. The area under receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values were used to assess the diagnostic accuracy of hippocampal volume in predicting fulfillment of Alzheimer neuropathologic criteria and differences in Braak staging. RESULTS: Hippocampal volume predicted fulfillment of neuropathologic criteria for AD for all 56 participants (p < 0.001): 24 sisters who were demented (p = 0.036); 32 sisters who remained nondemented (p < 0.001), 8 sisters who remained nondemented but had memory impairment (p < 0.001), and 24 sisters who were intact with regard to memory and cognition at the final examination prior to death (p = 0.003). In individuals who remained nondemented, hippocampal volume was a better indicator of AD neuropathology than a delayed memory measure. Among nondemented sisters, Braak stages III and VI were distinguishable from Braak stages II or lower (p = 0.001). Among cognitively intact individuals, those in Braak stage II could be distinguished from those in stage I or less (p = 0.025). CONCLUSION: Volumetric measures of the hippocampus may be useful in identifying nondemented individuals who satisfy neuropathologic criteria for AD as well as pathologic stages of AD that may be present decades before initial clinical expression.

Borenstein Graves A, Mortimer JA, Bowen JD, McCormick WC, McCurry SM, Schellenberg GD, Larson EB. · Department of Epidemiology and Biostatistics, University of South Florida, Tampa, 33612-3805, USA. · Neurology. · Pubmed #11673588 No free full text.

Abstract: BACKGROUND: The clinical expression of AD likely occurs when the accumulation of degeneration in specific brain regions leads to the descent below a critical threshold of "brain reserve" beyond which normal cognitive function cannot be maintained. The association between head circumference (HC), a measure of brain reserve, and the incidence of probable AD was examined in a large nondemented cohort that has been followed since 1992 and its modification by APOE epsilon 4 genotype. METHODS: Fifty-nine incident cases of probable AD were identified from 1,869 initially nondemented individuals seen at the baseline examination (1992 to 1994) and followed for a mean of 3.8 years. Variables measured at baseline included age, education, gender, HC, height, weight, and score on the National Adult Reading Test-Revised. APOE was genotyped at the time of the first biennial examination (1994 to 1996) and was available for 1,111 individuals in the cohort. Cox proportional hazard regression was performed to estimate hazard ratios (HR) for probable AD for HC and other covariates. RESULTS: Incident cases were significantly older, less educated, shorter, and lighter, had lower estimated verbal IQ scores, and were more likely to have at least one APOE epsilon 4 allele than unaffected individuals. The HR associated with the lowest tertile of HC (<21.4 inches) adjusted for education, gender, and APOE epsilon 4 was 2.3 (95% CI 0.7 to 6.9, p = 0.16). The HR for one or two APOE epsilon 4 alleles was significant (HR = 4.8, 95% CI 1.8 to 12.9, p = 0.002). The combination of low HC and APOE epsilon 4 strongly predicted earlier onset of AD with HR = 14.1 (95% CI 3.0 to 65, p = 0.0007). CONCLUSIONS: Smaller HC, in the presence of the APOE epsilon 4 allele, hastens the age at onset of AD. These results support the brain reserve hypothesis and its importance in precipitating the clinical expression of AD among genetically predisposed individuals.

Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA. · Institute on Aging, University of South Florida, Tampa 33612-3899, USA. · AJNR Am J Neuroradiol. · Pubmed #11673162 links to  free full text

Abstract: We describe an automated volumetric measure of the hippocampus obtained with software called the Knowledge-Guided MRI Analysis Program (KGMAP). Postmortem MR images from 56 participants in the Nun Study were used to validate the measure. KGMAP-determined volumes strongly correlated with those obtained with manual tracings and neurofibrillary pathologic findings of Alzheimer disease in the hippocampus. KGMAP provides a rapid and accurate estimate of hippocampal volume that is suitable for use in clinical practice.

Gatz M, Svedberg P, Pedersen NL, Mortimer JA, Berg S, Johansson B. · Department of Psychology, University of Southern California, Los Angeles, CA 90089-1061, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #11522804 No free full text.

Abstract: The association between dementia and education was studied in 143 twin pairs discordant for dementia, using a matched-pair design, and in 221 dementia cases and 442 unrelated controls from the same twin registry, using a case-control design. Low education was defined as 6 years or less of schooling. Case-control analyses with prevalent cases showed low education to be a risk for Alzheimer's disease but not dementia in general. Low education did not significantly predict incident cases. In the matched-pairs analysis, which controls for genetic and other familial influences, differences in education between demented twins and twin partners were not statistically significant. However, for Alzheimer's disease, odds ratios resulting from matched pairs and case-control analyses were similar. Twins' comparative reports about intellectual involvement earlier in their lives suggest a long-standing difference on this dimension, with less involvement by the twin who became demented.

Riley KP, Snowdon DA, Saunders AM, Roses AD, Mortimer JA, Nanayakkara N. · Sanders-Brown Center on Aging, College of Medicine, Lexington, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #10794191 No free full text.

Abstract: OBJECTIVES: The epsilon4 allele of apolipoprotein E (APOE) has been associated with Alzheimer' s disease and with milder forms of cognitive impairment. We investigated the possibility that the absence of the epsilon4 allele may predict the maintenance of high cognitive function among very old individuals. METHODS: Our data are from the Nun Study, a longitudinal study of aging and Alzheimer's disease in 678 Catholic sisters. All sisters participate in annual functional exams that include the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. High cognitive function was defined as intact scores on five of the CERAD tests. A total of 241 participants aged 75 to 98 met this criterion at the first exam. RESULTS: Findings showed that 62% of the 241 participants maintained intact scores on the five CERAD tests throughout their participation in the study. Life table analyses indicated that those without the APOE epsilon4 allele spent more time with intact cognitive function than those with the epsilon4 allele (p = .007). Cox regression analyses indicated that those without the epsilon4 allele had half the risk of losing their intact status during the study when compared with those with the epsilon4 allele (p < .01). DISCUSSION: Our findings suggest that the APOE epsilon4 allele may be included among the variables that predict high cognitive function in cognitively intact, very old adults. Although the presence or absence of the epsilon4 allele is known to be related to the risk of dementia, it also appears to be related to maintaining high levels of cognitive function in old age.

Joseph L, Wolfson DB, Bélisle P, Brooks JO, Mortimer JA, Tinklenberg JR, Yesavage JA. · Department of Epidemiology and Biostatistics, McGill University, Montreal General Hospital, Quebec, Canada. · Am J Epidemiol. · Pubmed #10342806 links to  free full text

Abstract: The pattern of deterioration in patients with Alzheimer's disease is highly variable within a given population. With recent speculation that the apolipoprotein E allele may influence rate of decline and claims that certain drugs may slow the course of the disease, there is a compelling need for sound statistical methodology to address these questions. Current statistical methods for describing decline do not adequately take into account between-patient variability and possible floor and/or ceiling effects in the scale measuring decline, and they fail to allow for uncertainty in disease onset. In this paper, the authors analyze longitudinal Mini-Mental State Examination scores from two groups of Alzheimer's disease subjects from Palo Alto, California, and Minneapolis, Minnesota, in 1981-1993 and 1986-1988, respectively. A Bayesian hierarchical model is introduced as an elegant means of simultaneously overcoming all of the difficulties referred to above.

Mortimer JA. · No affiliation provided · JAMA. · Pubmed #19155450 No free full text.

This publication has no abstract.