افسردگی و خطر ابتلا به دمانس آلزایمر: عوامل افزایش خطر در بزرگسالان مبتلا به افسردگی Depression and Risk of Alzheimer’s Dementia: a Longitudinal Analysis to Determine Predictors of Increased Risk among Older Adults with Depression

ntroduction Depression in later life has been associated with an approximate two-fold increased risk of Alzheimer’s dementia (AD) (1). However, depression is a heterogeneous disorder and it is not clear which clinical characteristics among older adults with depression are most closely associated with risk of AD. Several mechanisms of association have been proposed to explain the excess risk observed among older adults with depression. It has long been proposed chronic glucocorticoid exposure secondary to stress axis activation in depression may have direct neurotoxic effects. Some support for this proposition has been provided by studies documenting reductions in hippocampal volume among adults with persistent or recurrent depression (2). Inflammatory activation and oxidative stress frequently occur as part of the depressive syndrome and have been associated with accelerated cognitive decline (3, 4). Depression is often associated with a greater burden of vascular risk factors and bidirectional relationships between depression and vascular disease have been well described (5). Alternately it has been proposed that depression is not a true risk factor for AD but occurs as an early symptom of beta-amyloid deposition and neurodegenerative disease. In support of this, it has been observed that depression with first onset in later years is more likely to be associated with cognitive impairment and increased depressive symptoms have been noted in individuals with normal cognition and increased cerebral beta-amyloid burden (6, 7). Conversely several studies, including those with much longer durations of follow up, have reported an increased risk of AD among those with early onset depression. In theses studies an incremental risk has been reported according to number of previous depressive episodes and severity of symptoms (8-10). In the general population efforts to prevent or delay the onset of AD have largely focused upon individuals with mild cognitive impairment (MCI) and particularly those with amnestic MCI more frequently associated with early Alzheimer’s pathology. Depression has been reported to accelerate conversion from MCI to AD in a number population studies and therefore individuals with both depression and MCI potentially represent a high-risk group suitable for preventive interventions (11). However, findings from population studies may not be readily generalized to those attending specialist services as older adults referred to specialist clinics typically have more severe depression & greater co-morbidity (12). A relatively smaller number of studies in clinical samples have reported that between 8 – 85% of adults with depression and MCI may progress to AD (13, 14). The considerable variability observed in clinical studies likely reflects variations in patient samples and clinical processes between centers. To the best of our knowledge no study to date has undertaken a large-scale analysis, specifically focused upon older adults with depression and MCI attending specialized memory services utilizing standardized clinical processes to describe the overall risk of progression to AD. If we are to successfully reduce the incidence of AD in this vulnerable population, it will be critical to determine the overall risk of progression to AD among patients with depression and MCI. It will also be important to characterize subgroups at greatest risk according to characteristics of depression, MCI subtype & medical co-morbidities.