A history of depression is a risk factor for Alzheimer’s disease, rather than an early sign of its development, according to the results of two separate studies. Findings on the effect of depressive symptoms at baseline remain inconclusive, however, as one group of investigators reported that depression increased the incidence of Alzheimer’s disease and mild cognitive impairment during follow-up, while the other group reported that it did not.
In the first study, Monique Breteler, MD, PhD, a Professor at Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues randomly selected participants from the Rotterdam Scan Study ages 60 to 90 without dementia at baseline to be included. About 27% of the 486 subjects who completed the study reported a history of depression, of which 64.6% reported an early onset (younger than 60), said the investigators in the April 8 Neurology. Thirty-five subjects had a baseline Center for Epidemiologic Studies Depression Scale score of 16 or greater, which indicated presence of depressive symptoms. Volumetric assessments of the hippocampus and amygdala were also conducted at baseline with three-dimensional MRI.
Greatest Risk With Early Onset of Depression
“During a total of 2,854 person-years of follow-up (mean per person, 5.9 years), 44 persons developed dementia, 33 of whom developed Alzheimer’s disease,” said the authors. Having a history of depression increased the risk of Alzheimer’s disease (hazard ratio [HR], 2.46), which did not change after the researchers adjusted for hippocampal and amygdalar volume.
When the participants with a positive history of depression were categorized by early or late onset, Dr. Breteler and colleagues found that those with an early onset had an even greater risk for Alzheimer’s disease compared with those with no history (HR, 3.70), while the late-onset group still had an increased risk, albeit less pronounced (HR, 1.71). The researchers posited that early-onset depression and Alzheimer’s disease may not be causally related, but that another, unknown factor may lead to an increased risk for both diseases.
History of depression was not associated with hippocampal or amygdalar volumes, however, which Dr. Breteler’s group noted contrasts with a number of clinical studies in patients with major depression or PTSD. However, the authors suggested that they may have had too few participants with severe depression to find a significant relationship, or that the effect of depression is through other brain structures besides the hippocampus or amygdala. Symptoms of depression at baseline were also not observed to increase the risk of dementia or Alzheimer’s disease. A difference in depression measures from other studies that have observed such a relationship, the relatively young age of the participants in the present study, or the possibility that only severe depression may increase the risk of Alzheimer’s disease may explain the lack of an association, suggested the researchers.
Reverse Causality Hypothesis
In the second study, published in the April Archives of General Psychiatry, Robert S. Wilson, PhD, senior neuropsychologist at the Rush Alzheimer’s Disease Center in Chicago, and colleagues conducted an annual follow-up on 917 nuns, priests, and monks from the Religious Orders Study for up to 13 years. At baseline, more than half of the participants had no symptoms of depression, 23.9% reported one symptom, 9.7% reported two, 6.1% reported three, and 6.8% reported four or more. “A higher number of depressive symptoms was associated with older age but not with education or sex,” noted the authors.
During follow-up, 190 participants were diagnosed with Alzheimer’s disease after a mean of 3.9 years; these patients were older at baseline and had more depressive symptoms, lower levels of cognitive function, and more concern about their memory than those who remained unaffected.
“In this study, we tested an implication of the reverse causality hypothesis,” said Dr. Wilson and colleagues. “That is, if depressive symptoms predict loss of cognition because they are a consequence of the pathologic processes causing dementia or a reaction to declining function, depressive symptoms are likely to increase at some point before dementia is clinically evident.” However, there was no evidence of an increase in depressive symptoms in the three to four years prior to the onset of dementia, nor was there a statistically different rate of change in depressive symptoms in Alzheimer’s disease–affected versus –unaffected participants, they reported. Among those without cognitive impairment at baseline, there was no systematic increase in depressive symptoms in those who subsequently developed mild cognitive impairment, a recognized precursor to dementia in Alzheimer’s disease, although the group’s baseline depressive symptoms were significantly higher than those in the group that did not develop mild cognitive impairment.