ALZHEIMER'S DISEASE AND MEDICAL DISEASE CONDITIONS: A PROSPECTIVE COHORT STUDY (2005)

To the Editor: Patients with early Alzheimer's disease (AD) represent a heterogeneous cohort, with some patients progressing faster to end-stage dementia and some others progressing much more slowly (Table 1). It has been postulated that various factors such as Mini-Mental State Examination (MMSE) score on initial presentation, educational level, age of onset of AD, female sex, poor performance on activities of daily living, family history, and presence of psychiatric symptoms explain this difference.1,2 A prospective cohort study was designed to study the coexisting medical diseases at various stages of AD and to determine whether they have any effect on the progression of AD. A cohort of community-residing elderly persons aged 60 to 85 who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria for primary degenerative dementia of the Alzheimer's type3 and National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria4 for probable AD at baseline were followed longitudinally at intervals of 3 to 4 years. Medical, neurological, psychiatric, psychometric, and neuroradiological evaluations were conducted at baseline to exclude patients with other dementing illnesses. The Global Deterioration Scale (GDS)5 and the MMSE were used to assess the cognitive and functional capacity at all evaluations. Further evaluations were not performed once the person reached the final, most severe stage of AD (GDS 7). The course of dementia was considered rapid if GDS 7 was reached within 4 years of the time of baseline evaluation.6 Criteria for exclusion at baseline included history of head trauma; seizures or other neurological disorders; mental retardation; a diagnosis of multiinfarct dementia; significant alcohol abuse; schizophrenia, depression, or major affective disorders; and cardiac, pulmonary, vascular, metabolic, or hematological conditions or other impairments of sufficient severity to adversely affect cognition or functioning. The medical disease conditions (MDCs) were categorized as cardiovascular, endocrine, respiratory, nervous system (except dementia), hematological, neoplastic, gastrointestinal, dermatological and connective tissue disorders, allergic, history of surgeries, injuries and fractures, eye and ear, genitourinary and gynecological, and musculoskeletal disorders. The MDCs were reviewed at each visit, and their effect on the course of AD was investigated. Forty consecutive patients (7 men and 33 women) from this cohort had progressed to GDS 7 at the time the study results were analyzed and formed the study group. Of these, 28 progressed to end-stage dementia in a mean of 3.2 years and were determined to have a rapid course. The remaining 12 progressed more slowly to end-stage dementia, over a mean of 6.9 years. Patients whose decline was rapid had 6.0 MDCs at their baseline evaluation, which was significantly more than the 3.9 MDCs in patients whose course of dementia was slower. The patients in the rapid deterioration group suffered at baseline significantly more from peripheral vascular disease (36% vs 0%) and atherosclerotic heart disease (29% vs 8%) than those who progressed more slowly to end-stage AD. The incidence of diabetes mellitus and hypertension were significantly greater at baseline in the rapidly progressive group. Hip fractures, contractures, and decubiti were conditions that were not found at onset but had significantly higher incidence when end-stage AD was reached. This is the first prospective study, to the authors' knowledge, to report the prevalence of medical diseases in the various stages of AD and assess their effect on the progression of AD. The number of MDCs at baseline in patients with mild to moderate AD affected the progression, with higher disease burden (especially vascular disorders) causing rapid progression of AD. The clinical significance of these findings adds to the growing evidence of the importance of vascular disorders in cognitive decline.7,8 The strengths of the study were its prospective cohort design, systematic and extensive analysis of the comorbid conditions at various stages of AD, and follow-up of patients even when they were institutionalized. The limitations of the study were the small number of patients. This study has significant implications for clinical practice and public health. It clearly demonstrates the importance of addressing comorbid medical illnesses, especially vascular risk factors, in the management of AD. Patients who are diagnosed with mild to moderate dementia (GDS 4 or 5) progress more rapidly to end-stage dementia if they have more medical conditions at the time of their diagnosis, thus emphasizing the importance of holistic treatment of all medical diseases to help slow the progression of dementia. Financial Disclosure: The authors state that they have no financial disclosures to declare. There are no conflicts of interest in this letter. Author Contributions: Istvan Boksay contributed to study concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of the manuscript. Eszter Boksay was involved in the study concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. Barry Reisberg took part in the study concept and design, acquisition of subjects and data, and analysis and interpretation of data. Carol Torossian was the statistical analyst. Mahesh Krishnamurthy contributed to preparation of manuscript. Sponsor's Role: The sponsors did not take any role in writing this letter.