Is Depression A Risk Factor Or a Prodromal Symptom of Dementia?

Depressive symptoms likely do not increase the risk of dementia.

Depressive symptoms might be a prodromal feature of dementia or share common causes with dementia, according to the findings of a 28-year study.

A team of France- and United Kingdom-based researchers studied up to 10,308 individuals (age 35 to 55) who were recruited to the Whitehall II cohort study in 1985. At baseline, participants responded to a questionnaire and underwent a structured clinical evaluation that included measures of anthropometry as well as cardiovascular and metabolic risk factors and diseases. Follow-up assessments consisting of a mail questionnaire and clinical examination have taken place approximately every 5 years since then.

During 9 assessments, the researchers used the 30-item General Health Questionnaire (GHQ-30), and on 3 occasions used the 20-item Center for Epidemiologic Studies Depression Scale (CES-D) to determine the frequency and severity of depressive symptoms. They defined chronic/recurring GHQ-measured depressive symptoms in 2 ways: during the early phase of follow-up, they used data from 1985, 1989, and 1991; and during the late phase they used data from 1997, 2001, and 2003.

To assess rates of dementia, the researchers collected data from 3 national UK databases. They determined the validity of dementia cases by utilizing modeling changes in the global cognitive score, composed of tests of memory, reasoning, and phonemic and semantic fluency administered to participants in 1997, 2003, 2007, and 2012.

The researchers also included sociodemographic factors (age, sex, race/ethnicity, and education), health behaviors (smoking, physical activity, fruit/vegetable intake, and alcohol consumption), the presence of diabetes or cardiovascular disease and the use of certain medications such as antidepressants.

Of the original 10,308 participants, GHQ-30 data were available for 10,189 patients in 1985 and 6728 patients in 2003. Of the 3461 participants lost to follow- up over this period, 15.3% had died and 0.4% had a dementia diagnosis prior to 2003. Participants lacking data at the 2003 assessment were more likely to be older (44.9 vs 44.7 in 1985; P =0.04), women (41.1% vs 29.4%; P <.001), and without a university degree (79.6% vs 70.9%; P <.001).

Most cases of dementia occurred between 1995 and 2015, with 73% of cases recorded in the final 5 years of follow-up. Increasing age, female sex, and education less than secondary school diploma were associated with elevated dementia risk.

Participants with depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for dementia (hazard ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions. However, participants with depressive symptoms in 2003 (mean follow-up, 11 years) had an increased risk (HR, 1.72; 95% CI, 1.21-2.44).

While participants with chronic/recurring depressive symptoms (2 of 3 occasions) in the early study phase (mean follow-up, 22 years) did not have excess risk of dementia (HR, 1.02; 95%CI, 0.72-1.44), patients with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49).

When the researchers used mixed models and a backward time scale to analyze retrospective depressive trajectories over 28 years, they found that in patients with dementia differences in depressive symptoms became apparent 11 years before dementia diagnosis and increased 9-fold at the year of diagnosis compared with patients without dementia (difference, 0.61; 95% CI, 0.09-1.13; P =.02 and 5.81; 95%CI, 4.81-6.81; P <.001, respectively).

“These results showed an accelerated increase in depressive symptoms in the decade prior to dementia diagnosis, based on the GHQ-30,” the researchers commented, adding that the CES-D score trajectory, modeled up to 12 years before dementia diagnosis, also showed an increase in depressive symptoms.

They noted that even chronic/recurring midlife depressive symptoms, which were assessed during the early years of the study, were not associated with an increased risk for dementia. However, during the decade preceding diagnosis, depressive symptoms “amplified more than 9 times at dementia diagnosis.”

“Taken together, these findings are consistent with the hypothesis that depressive symptoms are a prodromal feature of dementia, or that the two share common causes. Thus, our findings do not support the hypothesis that depressive symptoms increase the risk for dementia,” they concluded.

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Singh-Manoux A, Dugravot A, Fournier A, et al. Trajectories of depressive symptoms before diagnosis of dementia: a 28-year follow-up study [published online May 17, 2017]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.0660.