دانلود رایگان مقاله انگلیسی افسردگی و خطر ابتلا به دمانس آلزایمر: عوامل افزایش خطر در بزرگسالان مبتلا به افسردگی - الزویر 2018

Abstract

Objective: Older adults with depression are at increased risk of Alzheimer’s dementia (AD) but predictors of increased risk remain incompletely understood. We aim to identify characteristics of older adults with depression most at most risk of progressing to AD. Identification of high-risk subgroups could facilitate future interventional strategies to reduce risk of AD in older adults with depression. Methods: Using data from the National Alzheimer’s Coordinating Centre, 1965 participants with clinically defined depression and Mild Cognitive Impairment (MCI) at baseline were followed until development of AD or loss to follow up. Results: 780 (39.7%) developed AD over a median follow up duration of 27 months. In survival analyses age (HR 1.04, 95% 1.03 – 1.05), baseline MMSE (HR 0.85, 95% CI 0.83 – 0.87), amnestic subtype of MCI (HR 1.66, 95% 1.30 – 2.12), presence of APOE e4 allele (HR 1.99, 1.69 – 2.36) and presence of active depression within the last 2 years (HR 1.44, 95% CI 1.16 – 1.79) were all independently associated with increased risk of AD. 656 (41.7%) participants with MCI and active depression within the last 2 years developed AD compared to 120 (31.6%) of those with a more remote history of depression. Conclusion: Older adults with depression and MCI demonstrated a high rate of progression to AD over a relatively short duration of follow up. Individuals with a combination of MCI and recently active depression are a particularly high-risk subgroup.

Discussion

In this longitudinal evaluation of older adults with depression and MCI, we found that a large proportion of patients (39.7%) progressed to AD over a relatively short median follow up duration of 27 months. This compares to an annual conversion rate of approximately 15% in a previous analysis of all participants with MCI in the NACC dataset (23). We also found that risk of progression to AD was significantly elevated in those who reported an active history of depression within the last two years compared to those with a more remote history of depression. Late onset depression has previously been associated with greater cognitive impairment (7, 24) but depression with earlier onset has also been associated with increased risk of AD (8, 10). With the advent of molecular imaging techniques a number of studies have demonstrated a positive correlation between increasing cerebral beta-amyloid and tau burden and depressive symptoms in individuals with normal cognition, supporting the proposition that depression may be one of the earliest symptoms Alzheimer’s pathology (6, 25, 26). In this sample it is likely that individuals with active depression within the last two years includes a combination of those with late onset depression (first onset > 50 – 60yrs of age) & those with earlier onset depression that has persisted or recurred at the time of baseline assessment. Therefore, the association between elevated risk and recency of depression does not preclude the possibility that depression with earlier onset remains a risk factor for AD. However, in this population at least, it appears that the presence of active depression within the last two years should be considered a marker of even greater risk, possibly reflecting more aggressive progression of underlying Alzheimer’s pathology. It is also possible that physiologic and behavioral changes associated with the depressive state accelerate cognitive decline at a time of increased vulnerability. Physical inactivity, inflammatory activation and oxidative stress have all been associated with cognitive decline (3, 4) while both endogenous and exogenous glucocorticoids have been associated with increased production of beta-amyloid in animal models (27).