The relationship between depression, mild cognitive impairment, and future risk of progression to dementia
The December International Psychogeriatrics Article of the Month is entitled ‘Amnestic mild cognitive impairment and incident dementia and Alzheimer’s disease in geriatric depression’ by David C Steffens, Douglas R McQuoid and Guy G Potter
In this month’s “Paper of the Month,” Steffens and colleagues report on the relationship between depression, mild cognitive impairment (MCI) and future risk of progression to dementia. It has long been known that there is a complex relationship between depression and cognitive impairment, with depression common in those with cognitive impairment and dementia, and subsequent cognitive decline frequent in patients with depression .
The study uses a large cohort, the Neurocognitive Outcomes of Depression in the Elderly study (NCODE) from Duke University to follow 295 depressed subjects and 161 controls over a mean six year period. They find that, using standard definitions of MCI, around 21% of the depressed group meet criteria for MCI compared to less than 3% of controls. Over the follow-up period, many more of those in the depressed group (14%) compared to controls (2%) subsequently developed dementia, this being Alzheimer’s disease in two thirds of cases.
Examining predictors, both age and the presence of amnestic MCI at baseline were strong predictors of progression, and interestingly age was a much stronger predictor in the multi-variate model than the presence of amnestic MCI, though both were significant. The large sample size and the long term follow-up are major strengths of the study.
The study provides important new information about the prevalence of amnestic MCI in a large group of older depressed subjects and confirms that, as with amnestic MCI in the absence of depression, the presence of amnestic MCI is a poor prognostic feature in terms of increasing the risk for progression to future dementia, most often Alzheimer’s disease.
Of course, one of the key questions is why subjects with late life depression are at increased risk of future cognitive decline and dementia, and whether amnestic MCI in depression has the same biological underpinnings as amnestic MCI in non-depressed subjects. The authors discuss possible mechanisms in the paper, including the fact that vascular factors, known to be more common in those with late life depression may be important, though the imaging of vascular changes was not examined in this report. Other potential mechanisms include possible neurotoxic effects of raised cortisol levels during depression, or the expression of depression as a prodromal state of Alzheimer’s disease.
Unfortunately, there have been very few pathological studies of subjects with late life depression to ascertain the likely cause of the structural brain atrophy which occurs, and further pathological studies would be very informative. In addition, the availability of CSF and imaging biomarkers for degenerative pathology now allow new mechanistic studies to be undertaken in late life depression to help elucidate correlates and mechanisms of cognitive decline.
Finally, as with Alzheimer’s disease, there is much interest in the possible role for neuroinflammation in depression which may provide a link between depression and cognitive decline. The outcomes of such mechanistic studies are not purely for scientific curiosity, but they will shed light on likely aetiological mechanisms, providing new targets towards which therapeutic interventions can be directed, with the aim of improving outcomes for those with late life depression and preventing future cognitive decline.
This blog post is a condensed version of the commentary on the paper written by John T. O’Brien.
The commentary on the paper, “Commentary on: amnestic mild cognitive impairment and incident dementia and Alzheimer’s disease in geriatric depression” is also available free of charge for a limited time here.