Depression in the Prodromal Phase of Alzheimer Disease and the Reverse Causal Hypothesis

It was a pleasure reading the article of Wilson et al¹ dealing with changes of depressive symptoms in the prodromal phase of Alzheimer disease (AD) in a large cohort of elderly subjects. They tested the reverse causality hypothesis, arguing that depression would be a consequence of the disease rather than a risk factor. The hypothesis is plausible from a biological standpoint and worthy of consideration since there is a continuum between normality, mild cognitive impairment, and AD. The follow-up period was long enough to detect an increase of depressive symptoms in the early phases of the disease. However, Wilson et al were unable to verify their hypothesis as no increases in depressive symptoms were detected before the diagnosis of AD was made. Aside from the possibility of low sensitivity of the self-reported instrument used to measure depressive symptoms in AD, increases in depressive symptoms were not observed in determined subgroups according to determined variables (perceived memory dysfunction, personality traits, and vascular disease).