Long Term Outcome and Prediction Models of Cognition, Activities of Daily Living and Nursing Home Placement in Alzheimer’s Disease with Cholinesterase Inhibitor Treatment

Background
Prospective longitudinal studies in Alzheimer's disease (AD) that include cholinesterase inhibitor (ChEI) treatment in routine clinical settings are scarce. The patients vary in severity of the disease, clinical course, rate of progression and response to treatment. Knowledge about the predicted course of the disease, sociodemographic and clinical factors affecting the outcome and the impact of ChEI therapy, could be valuable for clinicians and the social services. This information is also essential for clinical research and for evaluating new therapies.

Aims
Study aims are to investigate potential predictors of change, differences in long-term outcome and rates of decline, and the time to nursing home placement for ChEI-treated AD patients in clinical practice.

Material
Swedish Alzheimer Treatment Study - outpatients with a clinical dementia diagnosis, and probable or possible AD, were recruited from memory clinics across Sweden. Cognitive, global and Activities of Daily Living (ADL) assessments were performed at the start of ChEI treatment and every 6 months during the following 3 years.

I. 435 donepezil-treated patients
II. 843 patients treated with donepezil, rivastigmine or galantamine
III. 790 patients treated with donepezil, rivastigmine or galantamine
IV. 880 patients treated with donepezil, rivastigmine or galantamine

Results
I. Regression models predicted 3-year cognitive outcome in ChEI-treated patients with high accuracy at the group level, but not individual patient responses.
II. A higher dose of ChEI, male gender, older age, absence of the APOE ε4 allele or usage of NSAIDs/acetylsalicylic acid were predictors of improved cognitive response to ChEI treatment after 6 months, and of a more positive long-term outcome.
III. Lower cognitive status at baseline, older age, higher education level, and solitary living were identified as risk factors for faster decline in functional ability, whereas a higher dose of ChEI, regardless of drug agent, was related to a slower instrumental ADL decline.
IV. The rate of functional, but not cognitive, deterioration was a strong risk factor for nursing home placement. The males living alone, patients with a substantial increase in adult day care or those receiving a lower mean dose of ChEI during the study exhibited shorter time to institutionalization.

Conclusions
Instrumental ADL ability is an essential measure for predicting longitudinal outcome and nursing home placement in AD. Patients with more cognitive impairment and older individuals exhibited a better response to ChEI therapy, stressing the importance of treating these groups as well. A higher ChEI dose, irrespective of drug agent, could possibly lead to more favorable cognitive and functional outcomes.