Alzheimer Disease: Corcoran C

Rosenberg PB, Mielke MM, Tschanz J, Cook L, Corcoran C, Hayden KM, Norton M, Rabins PV, Green RC, Welsh-Bohmer KA, Breitner JC, Munger R, Lyketsos CG. · Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. · Am J Geriatr Psychiatry. · Pubmed #18978249 links to  free full text

Abstract: BACKGROUND: Evidence suggests that cardiovascular medications, including statins and antihypertensive medications, may delay cognitive decline in patients with Alzheimer dementia (AD). We examined the association of cardiovascular medication use and rate of functional decline in a population-based cohort of individuals with incident AD. METHODS: In the Dementia Progression Study of the Cache County Study on Memory, Health, and Aging, 216 individuals with incident AD were identified and followed longitudinally with in-home visits for a mean of 3.0 years and 2.1 follow-up visits. The Clinical Dementia Rating (CDR) was completed at each follow-up. Medication use was inventoried during in-home visits. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) as the outcome and cardiovascular medication use as the major predictors. RESULTS: CDR-Sum increased an average of 1.69 points annually, indicating a steady decline in functioning. After adjustment for demographic variables and the baseline presence of cardiovascular conditions, use of statins (p = 0.03) and beta-blockers (p = 0.04) was associated with a slower annual rate of increase in CDR-Sum (slower rate of functional decline) of 0.75 and 0.68 points respectively, while diuretic use was associated with a faster rate of increase in CDR-Sum (p = 0.01; 0.96 points annually). Use of calcium-channel blockers, angiotensin-converting enzyme inhibitors, digoxin, or nitrates did not affect the rate of functional decline. CONCLUSIONS: In this population-based study of individuals with incident AD, use of statins and beta-blockers was associated with delay of functional decline. Further studies are needed to confirm these results and to determine whether treatment with these medications may help delay AD progression.

Treiber KA, Lyketsos CG, Corcoran C, Steinberg M, Norton M, Green RC, Rabins P, Stein DM, Welsh-Bohmer KA, Breitner JC, Tschanz JT. · Department of Psychology, Utah State University, Logan, U.S.A. · Int Psychogeriatr. · Pubmed #18289451 links to  free full text

Abstract: OBJECTIVE: To examine, in an exploratory analysis, the association between vascular conditions and the occurrence of neuropsychiatric symptoms (NPS) in a population-based sample of incident Alzheimer's disease (AD). METHODS: The sample consisted of 254 participants, identified through two waves of assessment. NPS were assessed using the Neuropsychiatric Inventory. Prior to the onset of AD, data regarding a history of stroke, hypertension, hyperlipidemia, heart attack or coronary artery bypass graft (CABG), and diabetes were recorded. Logistic regression procedures were used to examine the relationship of each vascular condition to individual neuropsychiatric symptoms. Covariates considered were age, gender, education, APOE genotype, dementia severity, and overall health status. RESULTS: One or more NPS were observed in 51% of participants. Depression was most common (25.8%), followed by apathy (18.6%), and irritability (17.7%). Least common were elation (0.8%), hallucinations (5.6%), and disinhibition (6.0%). Stroke prior to the onset of AD was associated with increased risk of delusions (OR = 4.76, p = 0.02), depression (OR = 3.87, p = 0.03), and apathy (OR = 4.48, p = 0.02). Hypertension was associated with increased risk of delusions (OR = 2.34, p = 0.02), anxiety (OR = 4.10, p = 0.002), and agitation/aggression (OR = 2.82, p = 0.01). No associations were observed between NPS and diabetes, hyperlipidemia, heart attack or CABG, or overall health. CONCLUSIONS: Results suggest that a history of stroke and hypertension increase the risk of specific NPS in patients with AD. These conditions may disrupt neural circuitry in brain areas involved in NPS. Findings may provide an avenue for reduction in occurrence of NPS through the treatment or prevention of vascular risk conditions.

Mielke MM, Rosenberg PB, Tschanz J, Cook L, Corcoran C, Hayden KM, Norton M, Rabins PV, Green RC, Welsh-Bohmer KA, Breitner JC, Munger R, Lyketsos CG. · Johns Hopkins University School of Medicine, Department of Psychiatry, Division of Geriatric Psychiatry and Behavioral Sciences, 550 N. Broadway, Suite 308, Baltimore, MD 21205, USA. · Neurology. · Pubmed #17984453 No free full text.

Abstract: BACKGROUND: While there is considerable epidemiologic evidence that cardiovascular risk factors increase risk of incident Alzheimer disease (AD), few studies have examined their effect on progression after an established AD diagnosis. OBJECTIVE: To examine the effect of vascular factors, and potential age modification, on rate of progression in a longitudinal study of incident dementia. METHODS: A total of 135 individuals with incident AD, identified in a population-based sample of elderly persons in Cache County, UT, were followed with in-home visits for a mean of 3.0 years (range: 0.8 to 9.5) and 2.1 follow-up visits (range: 1 to 5). The Clinical Dementia Rating (CDR) Scale and Mini-Mental State Examination (MMSE) were administered at each visit. Baseline vascular factors were determined by interview and physical examination. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) or MMSE as the outcome, and vascular index or individual vascular factors as independent variables. RESULTS: Atrial fibrillation, systolic hypertension, and angina were associated with more rapid decline on both the CDR-Sum and MMSE, while history of coronary artery bypass graft surgery, diabetes, and antihypertensive medications were associated with a slower rate of decline. There was an age interaction such that systolic hypertension, angina, and myocardial infarction were associated with greater decline with increasing baseline age. CONCLUSION: Atrial fibrillation, hypertension, and angina were associated with a greater rate of decline and may represent modifiable risk factors for secondary prevention in Alzheimer disease. The attenuated decline for diabetes and coronary artery bypass graft surgery may be due to selective survival. Some of these effects appear to vary with age.

Hayden KM, Zandi PP, Khachaturian AS, Szekely CA, Fotuhi M, Norton MC, Tschanz JT, Pieper CF, Corcoran C, Lyketsos CG, Breitner JC, Welsh-Bohmer KA, Anonymous00160. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA. · Neurology. · Pubmed #17636065 No free full text.

Abstract: BACKGROUND: Epidemiologic studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful for the prevention of Alzheimer disease (AD). By contrast, clinical trials have not supported NSAID use to delay or treat AD. Few studies have evaluated cognitive trajectories of NSAID users over time. METHODS: Residents of Cache County, UT, aged 65 or older on January 1, 1995, were invited to participate in the study. At baseline, participants provided a detailed inventory of their medications and completed a revised Modified Mini-Mental State Examination (3MS). Participants (n = 3,383) who were cognitively normal at baseline were re-examined after 3 and 8 years. The association between NSAID use and 3MS scores over time was estimated using random effects modeling. RESULTS: Associations depended upon when NSAIDs were started and APOE genotype. In participants who started NSAID use prior to age 65, those with no APOE epsilon4 alleles performed similarly to nonusers (a difference of 0.10 points per year; p = 0.19), while those with one or more epsilon4 allele(s) showed more protection (0.40 points per year; p = 0.0005). Among participants who first used NSAIDs at or after age 65, those with one or more epsilon4 alleles had higher baseline scores (0.95 points; p = 0.03) but did not show subsequent difference in change in score over time (0.06 points per year; p = 0.56). Those without an epsilon4 allele who started NSAID use after age 65 showed greater decline than nonusers (-0.16 points per year; p = 0.02). CONCLUSIONS: Nonsteroidal anti-inflammatory drug use may help to prevent cognitive decline in older adults if started in midlife rather than late life. This effect may be more notable in those who have one or more APOE epsilon4 alleles.

Steinberg M, Corcoran C, Tschanz JT, Huber C, Welsh-Bohmer K, Norton MC, Zandi P, Breitner JC, Steffens DC, Lyketsos CG. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Int J Geriatr Psychiatry. · Pubmed #16955439 No free full text.

Abstract: OBJECTIVE: To investigate the probability of individual neuropsychiatric symptoms in dementia patients as a function of eight risk factors. METHODS: In the Cache County Study, we administered the Neuropsychiatric Inventory (NPI) to 328 dementia patients at baseline. Approximately 18 months later, we re-administered the NPI to 184 participants available for follow-up. Generalized estimating equation methods were used to model the probability of individual neuropsychiatric symptoms as a function of: gender, age, education, dementia type and severity, APOE status, time of observation, and general medical health. RESULTS: Women showed increased tendency toward anxiety, [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.31-3.76] and delusions (OR 2.15, CI 1.22-3.78), but older persons of both sexes showed less tendency toward anxiety. Dementia severity increased the tendency toward hallucinations and agitation (OR 2.42, CI 1.81-3.23) and decreased risk of depression. Positive APOE epsilon4 status increased the tendency toward aberrant motor behavior (OR 1.84, CI 1.05-3.22). Among dementia diagnoses, those with Alzheimer's disease showed decreased tendency toward agitation (OR 0.58, CI 0.35-0.95), depression (OR 0.56, CI 0.33-0.96) and disinhibition (OR 0.46, CI 0.24-0.88). Later time of observation increased risk of aberrant motor behavior and delusions, and more serious medical comorbidity increased risk of, agitation, irritability, disinhibition, and aberrant motor behavior. CONCLUSIONS: Gender, age, dementia severity, APOE epsilon4, dementia diagnosis, time of observation, and general medical health appear to influence the occurrence of individual neuropsychiatric symptoms.

Tschanz JT, Welsh-Bohmer KA, Lyketsos CG, Corcoran C, Green RC, Hayden K, Norton MC, Zandi PP, Toone L, West NA, Breitner JC, Anonymous00113. · Department of Psychology, Utah State University, Logan, USA. · Neurology. · Pubmed #16864813 No free full text.

Abstract: OBJECTIVE: To examine 3-year rates of conversion to dementia, and risk factors for such conversion, in a population-based sample with diverse types of cognitive impairment. METHODS: All elderly (aged 65 or older) residents of Cache County, UT, were invited to undergo two waves of dementia screening and assessment. Three-year follow-up data were available for 120 participants who had some form of mild cognitive impairment at baseline. Of these, 51 had been classified at baseline with prodromal Alzheimer disease (proAD), and 69 with other cognitive syndromes (CS). RESULTS: Three-year rates of conversion to dementia were 46% among those with cognitive impairment at baseline. By comparison, 3.3% without impairment converted to dementia in the interval. Among converters, AD was the most common type of dementia. In individuals with at least one APOE epsilon4 allele, those with proAD or CS exhibited a 22- to 25-fold higher risk of dementia than cognitively unimpaired individuals (vs 5- to 10-fold higher risk in those without epsilon4). CONCLUSIONS: Individuals with all types of mild cognitive impairment have an elevated risk of dementia over 3 years, more so in those with an APOE epsilon4 allele. These results suggest value in dementia surveillance for broad groups of cognitively impaired individuals beyond any specific category, and utility of APOE genotyping as a prognostic method.

Lyketsos CG, Toone L, Tschanz J, Rabins PV, Steinberg M, Onyike CU, Corcoran C, Norton M, Zandi P, Breitner JC, Welsh-Bohmer K, Anthony J, Østbye T, Bigler E, Pieper C, Burke J, Plassman B, Green RC, Steffens DC, Klein L, Leslie C, Townsend JJ, Wyse BW, Munger R, Williams M, Anonymous00077. · Division of Geriatric Psychiatry and Neuropsychiatry, Dept. of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Johns Hopkins Hospital, Baltimore, MD 21287, USA. · Am J Geriatr Psychiatry. · Pubmed #16085781 No free full text.

Abstract: OBJECTIVE: Authors investigated medical comorbidity in persons with dementia and "Cognitive Impairment, No Dementia" (CIND). METHODS: The Cache County Study is an ongoing population-based study of the epidemiology of dementia, the risk factors for conversion from CIND to dementia, and the progression of dementia. As part of the study's first incidence wave, persons with dementia (N=149), CIND (N=225), or without cognitive impairment (N=321) were identified and studied. Participants received comprehensive clinical evaluations and were rated on the General Medical Health Rating (GMHR), a global measure of seriousness of medical comorbidity. Participants and informants also completed the Mini-Mental State Exam and provided self-report information about comorbid medical conditions and functioning in activities of daily living. RESULTS: There were few differences in number or type of comorbid medical conditions between persons with CIND and dementia, but persons with dementia were prescribed more medications. Stroke was more common in dementia participants, but other illnesses common in old age were not significantly different across cognitive groups. Medical comorbidity was more serious in both dementia and CIND, such that both groups were less likely to have "little to no" comorbidity. Seriousness of medical comorbidity was significantly associated with worse day-to-day functioning and cognition. CONCLUSIONS: Persons with CIND and dementia have more serious medical comorbidity than comparable persons without cognitive impairment. This comorbidity may play a role in the progression of CIND and dementia. Future studies should investigate the role of medical comorbidity and its treatment on dementia onset or progression, as well as the mechanisms mediating its neuropathologic effects.

Tschanz JT, Corcoran C, Skoog I, Khachaturian AS, Herrick J, Hayden KM, Welsh-Bohmer KA, Calvert T, Norton MC, Zandi P, Breitner JC, Anonymous00121. · Center for Epidemiologic Studies, Department of Psychology, Utah State University, Logan 84322-4440, USA. · Neurology. · Pubmed #15079016 No free full text.

Abstract: OBJECTIVE: To examine the relative risk and population attributable risk (PAR) of death with dementia of varying type and severity and other risk factors in a population of exceptional longevity. METHODS: Deaths were monitored over 5 years using vital statistics records and newspaper obituaries in 355 individuals with prevalent dementia and 4,328 without in Cache County, UT. Mean age was 83.3 (SD 7.0) years with dementia and 73.7 (SD 6.8) years without. History of coronary artery disease, hypertension, diabetes, and other life-shortening illness was ascertained from interviews. RESULTS: Death certificates implicated dementia as an important cause of death, but other data suggested a stronger association. Adjusted Cox relative hazard and PAR of death were higher with dementia than with any other illness studied. Relative hazard of death with dementia was highest at ages 65 to 74, but the high prevalence of dementia after age 85 resulted in 27% PAR among the oldest old. Mortality increased substantially with severity of dementia. Alzheimer disease shortened survival time most dramatically in younger participants, but vascular dementia posed a greater mortality risk among the oldest old. CONCLUSION: In this population, dementia was the strongest predictor of mortality, with a risk two to three times those of other life-shortening illnesses.

Steffens DC, Norton MC, Hart AD, Skoog I, Corcoran C, Breitner JC, Anonymous00043. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. · Psychol Med. · Pubmed #12701674 No free full text.

Abstract: BACKGROUND: The role of allelic variation in APOE, the genetic locus for apolipoprotein E, in geriatric depression is poorly understood. There are conflicting reports as to an association between the epsilon4 allele and depression in late life. METHOD: Using a community based study of non-demented elders in Cache County, Utah, that included many very old individuals, we examined the relationship between APOE and late-onset (age > 60) depression, with particular attention to possible age effects. RESULTS: There was no overall association between APOE and depression. However, there was a significant interaction effect of APOE and age such that the relationship of late-onset depression with respect to presence of the epsilon4 allele was larger among those 80 and older compared with those below age 80. Consistent with previous studies, women were more likely to experience late-onset depression than men. CONCLUSIONS: Because we excluded prevalent cases of dementia, this pattern of relative risk with age may reflect the appearance of depressive symptoms as a prodrome of Alzheimer's disease or vascular dementia. Longitudinal studies should help to confirm or refute this explanation of the data.