COMORBIDITY IN ALZHEIMER'S DISEASE: A NESTED CASE-CONTROL STUDY

Abstract

We aimed to describe the multiplicity of chronic diseases in Alzheimer disease (AD) in a nested case-control study. We used a random sample of 1 million individuals from the year 2000 registration data in Taiwan National Health Insurance program to describe the comorbid pattern among patients with dementia during 2001-2011. Incident dementia was identified by International Classification of Diseases, Ninth Revision, first ever coded after 2001. Incident AD was further restricted to those treated with cholinesterase inhibitors or memantine of approved reimbursement. We selected 14 comorbid medical diseases with reference to the list of multiple chronic conditions developed by the US Department of Health and Human Services. Incident dementia and AD cases were age- and sex-matched to a set of control subjects (1: 2 ratio). We described the frequency and pattern of comorbidity in AD and validated in a smaller sample from a regional hospital by in-person interview and medical records review. We employed conditional logistic regression to estimate the associations between chronic diseases and AD. A total of 16,381 incident dementia cases were identified during 2001-2011 with mean age at 76.1 years (SD=10.5) and female preponderance (52%). About 8% of these dementia cases were deemed AD with approved AD drug reimbursement. The most common 5 comorbidities in AD were hypertension (54%), osteoarthritis (38%), depression (32%), diabetes mellitus (27%) and cerebrovascular diseases (24%); and they were also more often associated with AD cases than their matched controls after adjusting for age and sex (respective odds ratios: 1.36, 1.44, 3.23, 1.51, 2.26, p < 0.001). The number of comorbidity was 3-fold greater (p < 0.001) in the AD group (median: 3; range: 0-8) than the control group (median: 1; range: 0-10). Multimorbidity in AD is very common. Cerebrovascular risks are associated with AD even among those relatively “pure” cases deemed eligible for AD drug reimbursement, supporting that the co-existence is a typical feature of AD at old age and integrated medical care is much needed.