Predictors of Rapid Cognitive Decline in Patients with Mild-to-Moderate Alzheimer Disease: A Prospective Cohort Study with 12-Month Follow-Up Performed in Memory Clinics.

Background/aims: Alzheimer disease (AD) is particularly devastating, with no cure, no means of prevention, and no proven way to slow progression. AD is associated with the worsening of cognitive function attributable to a variety of factors of which little is known. Our main objective was to determine factors associated with rapid cognitive decline (RCD) in older AD patients.

Methods: We conducted a 12-month, prospective, multi-centre cohort study. Community-living individuals aged ≥65 years with mild-to-moderate AD were included. RCD was defined as the loss of ≥3 points/year in the Mini-Mental State Examination (MMSE) score. Potential individual-level predictors were collected at baseline.

Results: A total of 521 individuals were included. The mean age was 80.8 ± 9.0 years and 66.0% were females. The average baseline MMSE score was 20.5 ± 4.5. The incidence of RCD was 40.9% (95% confidence interval [CI], 36.7-45.1). RCD was more common in patients with moderate (53.5%) than mild (22.3%) AD. The factors associated with RCD were: a parental history of dementia (odds ratio [OR], 2.32 [95% CI, 1.24-4.21], p = 0.011), psychotic symptoms (OR, 2.06 [95% CI, 1.22-3.48], p = 0.007), malnutrition (OR, 1.61 [95% CI, 1.06-2.63], p = 0.028), and the female gender (OR, 1.48 [95% CI, 1.03-2.15], p = 0.036). An MMSE score < 20 at treatment onset was also associated with RCD (p < 0.001).

Conclusion: The factors associated with RCD were an MMSE score < 20 at treatment onset, female gender, psychotic symptoms, malnutrition, and a family history of dementia. These results may be directly relevant to patients, their families, and their physicians, enabling early anticipation of difficult clinical trajectories and poor functional outcomes.