The natural history of Alzheimer's disease: a brain bank study

To define the natural history of Alzheimer's Disease (AD), from time of clinical (presumptive) diagnosis and/or onset of symptoms to death and to describe demographic and clinical characteristics of patients with AD.

Retrospective medical records review.

Regional brain bank operated by a university hospital.

One-hundred randomly selected, autopsy-confirmed Alzheimer's Disease patients.

All information pertaining to family and clinical history (diagnoses, office visits, hospitalizations), medication use, nutritional status, and clinical testing (laboratory testing, imaging, diagnostics, and psychometric testing) was abstracted. Time of onset for behavioral symptoms (e.g., anxiety, wandering, agitation) and deficits in cognitive function (e.g., recent memory, concentration, language) and activities of daily living (ADL) were also abstracted. Data was collected on-site using a laptop computer and a series of customized data entry spreadsheets. Upon completion of the data abstraction process, data was converted to a database program for query and analysis.

A complete natural history timeline was constructed based on the mean values observed in order to demonstrate important clinical endpoints, namely, diagnosis, institutionalization, and death. The mean time between onset of symptoms and clinical diagnosis was 32.1 months (standard deviation = 37.9 months). The interval between symptom onset and AD diagnosis was longer for patients who were less than 65 at time of diagnosis (mean = 37.6 months), female patients (mean = 34.9 months), and patients with a positive family history of dementia (mean = 37.5 months). The mean age at diagnosis was 74.7 years (standard deviation = 8.6 years), with a range of 52 to 89 years. Most patients were diagnosed between the ages of 70 and 79. Males were diagnosed at an earlier age, 72.8 years, on average, than females, 75.4 years. The mean time to institutionalization from time of clinical diagnosis was 23.9 months (standard deviation = 33.6 months). The average age at institutionalization was 77.6 years, with a minimum of 60 years and a maximum of 92.5 years. Institutionalization occurred 56.5 months after symptom onset, on average. This interval was shorter among patients with a negative family history (mean = 53.1 months) and patients diagnosed after age 65 (mean = 51.6 months). Patients diagnosed before age 65 experienced a significantly greater average time to institutionalization, 94 months (P = .01). Disease duration was measured as time from symptom onset until death. Mean disease duration was 101.3 months, or nearly 8.5 years (standard deviation = 59.2 months). Subgroup analysis showed that disease duration was prolonged in younger onset patients (mean = 129.1 months), females (mean = 107.9 months), and patients with a positive family history of dementia (mean = 106.3 months).

These data suggest that the typical AD patient is diagnosed 32 months after symptom onset, at the age of 75 years. This patient is institutionalized 25 months after diagnosis, or approximately 57 months after symptom onset at age 78. The patient remains institutionalized for 44 months or, in actuality, until death. Total disease duration for this typical AD patient is just over 101 months, or approximately 8.5 years.