Longitudinal Course of Agitation and Aggression in Patients with Alzheimer's Disease in a Cohort Study: Methods, Baseline and Longitudinal Results of the A3C Study.

BACKGROUND

To present methodology, baseline results and longitudinal course of the Agitation and Aggression in patients with Alzheimer's Disease Cohort (A3C) study.

OBJECTIVES

The central objective of A3C was to study the course, over 12 months of clinically significant Agitation and Aggression symptoms based on validated measures, and to assess relationships between symptoms and clinical significance based on global ratings.

DESIGN

A3C is a longitudinal, prospective, multicenter observational cohort study performed at eight memory clinics in France, and their associated long-term care facilities.

SETTING

Clinical visits were scheduled at baseline, monthly during the first 3 months, at 6 months, at 9 months and at 12 months. The first three months intended to simulate a classic randomized control trial 12-week treatment design.

PARTICIPANTS

Alzheimer's Disease patients with clinically significant Agitation and Aggression symptoms lived at home or in long-term care facilities.

MEASUREMENTS

Clinically significant Agitation and Aggression symptoms were rated on Neuropsychiatric Inventory (NPI), NPI-Clinician rating (NPI-C) Agitation and Aggression domains, and Cohen Mansfield Agitation Inventory. Global rating of agitation over time was based on the modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. International Psychogeriatric Association "Provisional Diagnostic Criteria for Agitation", socio-demographics, non-pharmacological approaches, psychotropic medication use, resource utilization, quality of life, cognitive and physical status were assessed.

RESULTS

A3C enrolled 262 AD patients with a mean age of 82.4 years (SD ±7.2 years), 58.4% women, 69.9% at home. At baseline, mean MMSE score was 10.0 (SD±8.0), Cohen Mansfield Agitation Inventory score was 62.0 (SD±15.8) and NPI-C Agitation and Aggression clinician severity score was 15.8 (SD±10.8). According to the International Psychogeriatric Association agitation definition, more than 70% of participants showed excessive motor activity (n=199, 76.3%) and/or a verbal aggression (n=199, 76.3%) while 115 (44.1%) displayed physical aggression. The change of the CMAI score and the NPI-C Agitation and Aggression at 1-year follow-up period was respectively -11.36 (Standard Error (SE)=1.32; p<0.001) and -6.72 (SE=0.77; p<0.001).

CONCLUSION

Little is known about the longitudinal course of clinically significant agitation symptoms in Alzheimer's Disease about the variability in different outcome measures over time, or the definition of a clinically meaningful improvement. A3C may provide useful data to optimize future clinical trials and guide treatment development for Agitation and Aggression in Alzheimer's Disease.

Déclaration de conflit d'intérêts

C. Lyketsos declares: 1) Grant support (research or CME) from NIH, Functional Neuromodulation, Bright Focus Foundation and 2) Payment as consultant or advisor from Avanir, Astellas, Roche, Karuna, SVB Leerink, Maplight, Axsome, Global Institute on Addictions. None conflict for the others authors.