Alzheimer Disease: Norton M

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.

Fearing MA, Bigler ED, Norton M, Tschanz JA, Hulette C, Leslie C, Welsh-Bohmer K, Anonymous00112. · Brigham Young University, Provo, UT 84602-5543, USA. · J Clin Exp Neuropsychol. · Pubmed #17564920 No free full text.

Abstract: Atrophy of specific, regional, and generalized brain structures occurs as a result of the Alzheimer's disease (AD) process. Comparing AD patients with histopathological confirmation of the disease at autopsy to those without autopsy but who were clinically diagnosed using the same antemortem criteria will provide further evidence of the utility and accuracy of neuropsychological assessments at the time of diagnosis, as well as the efficacy of quantitative magnetic resonance imaging (qMRI) in demonstrating gross neuropathological changes associated with the disease. The Cache County Study of Aging provides a unique opportunity to determine how closely AD subjects with only the clinical diagnosis match similarly diagnosed AD subjects but with postmortem confirmation of the disease. qMRI volumes of various brain structures, as well as neuropsychological outcome measures from an expanded battery, were obtained in 31 autopsy-confirmed AD subjects and 45 clinically diagnosed AD subjects. Of the various qMRI variables examined, only total temporal lobe volume was different, where those with postmortem confirmation had reduced volume. No significant differences between the two groups were found with any of the neuropsychological outcome measures. These findings confirm the similarity in neuroimaging and neuropsychological assessment findings between those with just the clinical diagnosis of AD and those with an autopsy-confirmed diagnosis in the moderate-to-severe stage of the disease at the time of diagnosis.

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.

Zandi PP, Sparks DL, Khachaturian AS, Tschanz J, Norton M, Steinberg M, Welsh-Bohmer KA, Breitner JC, Anonymous00196. · Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. · Arch Gen Psychiatry. · Pubmed #15699299 links to  free full text

Abstract: BACKGROUND: Prior reports suggest reduced occurrence of dementia and Alzheimer disease (AD) in statin users, but, to our knowledge, no prospective studies relate statin use and dementia incidence. OBJECTIVE: To examine the association of statin use with both prevalence and incidence of dementia and AD. DESIGN: Cross-sectional studies of prevalence and incidence and a prospective study of incidence of dementia and AD among 5092 elderly residents (aged 65 years or older) of a single county. Participants were assessed at home in 1995-1997 and again in 1998-2000. A detailed visual inventory of medicines, including statins and other lipid-lowering agents, was collected at both assessments. MAIN OUTCOME MEASURES: Diagnosis of dementia and of AD. RESULTS: From 4895 participants with data sufficient to determine cognitive status, we identified 355 cases of prevalent dementia (200 with AD) at initial assessment. Statin use was inversely associated with prevalence of dementia (adjusted odds ratio, 0.44; 95% confidence interval, 0.17-0.94). Three years later, we identified 185 cases of incident dementia (104 with AD) among 3308 survivors at risk. Statin use at baseline did not predict incidence of dementia or AD (adjusted hazard ratio for dementia, 1.19; 95% confidence interval, 0.53-2.34; adjusted hazard ratio for AD, 1.19; 95% confidence interval, 0.35-2.96), nor did statin use at follow-up (adjusted odds ratio for dementia, 1.04; 95% confidence interval, 0.56-1.81; adjusted odds ratio for AD, 0.85; 95% confidence interval, 0.32-1.88). CONCLUSIONS: Although statin use might be less frequent in those with prevalent dementia, we found no association between statin use and subsequent onset of dementia or AD. Further research is warranted before costly dementia prevention trials with statins are undertaken.