Could Depression Trajectory Predict Higher Risk of Dementia?

Patients with increasing or worsening depressive symptoms were at a higher risk of dementia, whereas people suffering from high depressive symptoms at a single time point were not at a higher dementia risk than those without depressive symptoms, according to a new study. In the group with worsening depressive symptoms, about 1 in 5 people developed dementia during follow-up.

“The hypothesis that depressive symptoms in older adults represent a prodrome of dementia has been there for a considerable time now,” said lead author Saira Saeed Mirza, MD, PhD, of the Department of Epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands. “However, our results were especially remarkable because with repeated measures of depression, we could clearly show how depressive symptoms escalated over many years preceding dementia incidence. This was a novel finding to present and had not shown in any previous studies.”
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In the current study–embedded in the Rotterdam Study–the researchers examined a cohort of participants free from dementia but had data for depressive symptoms from at least 1 examination round in 1993-1995, 1997-1999, or 2002-2004. They assessed depressive symptoms with the validated Dutch version of the Center for Epidemiology Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale-Depression.

The investigators used these data to identify 11-year trajectories of depressive symptoms by latent class trajectory modeling. They screened participants for dementia at each examination round and followed up with them for 10 years for incident dementia by latent trajectory from the third examination round to 2014. They calculated hazard ratios (HR) for dementia by assigned trajectory using 2 Cox proportional hazards models. The researchers repeated the analyses censoring for incident stroke, restricting to Alzheimer disease as an outcome, and accounting for mortality as a competing risk for dementia.

From 1993-2004, they obtained data for depressive symptoms from at least 1 examination round for 3325 participants (median age: 74-88 years [interquartile range, 70.62-80.06], 1995 [60%] women). The researchers identified 5 trajectories of depressive symptoms in these individuals, characterized by maintained low CES-D scores (low; 2441 [73%]); moderately high starting scores but then remitting (decreasing; 369 [11%]); low starting scores, increasing, then remitting (remitting; 170 [5%]); low starting scores that steadily increased (increasing; 255 [8%]); and maintained high scores (high; 90 [3%]).

During 26,330 person-years, 434 participants developed incident dementia. They found only the trajectory with increasing depressive symptoms to be associated with a higher risk of dementia compared with the low depressive symptom trajectory, using model 2 (HR 1.42; 95% confidence interval, 1.05-1.94; p=0.024). Additionally, only the increasing trajectory was associated with a higher risk of dementia compared with the low trajectory after censoring for incident stroke (1.58, 1.15-2.16; P=.0041), restricting to Alzheimer disease as an outcome (1.44, 1.03-2.02; P=.034), and accounting for mortality as a competing risk (1.45, 1.06-1.97; P=.019).

“One of the key messages of this study is that in order to study long-term health outcomes related to depression or depressive symptoms, it is essential to study the course of depression, as it is a remitting and relapsing disorder,” Dr Mirza said. “Symptoms of depression do not remain the same over time, and thus, assessing it at a single time point only in such long follow-up studies cannot capture the real effects of the disease. Low depressive symptoms or symptoms that fluctuate overtime may not have a lasting influence on health and may not be a sign of underlying pathological changes related to dementia, but worsening symptoms of depression in older adults may be an early indicator of dementia and require attention.”

The researchers will continue to investigate the pathology of dementia and possible links between depression and dementia, Dr Mirza said. “We aim to find ways and design studies to examine not only biological factors, such as vascular disease, inflammation, and stress-related markers, but also lifestyle factors, such as physical activity and social networking, as potential risk factors of dementia and possible links between depression and dementia.”

–Mike Bederka

Reference:

Mirza SS, Wolters FJ, Swanson SA, et al. 10-year trajectories of depressive symptoms and risk of dementia: a population-based study. Lancet Psychiatry. 2016;3(7):628-635.