Even low levels of depressive symptoms are associated with an increased risk of cognitive decline in older adults without overt cognitive impairment (CN). GDS total score age sex premorbid intelligence a binary amyloid variable and its interaction with GDS. Principal component analyses of GDS item scores revealed three factors (the Dysphoria Apathy-Anhedonia and Anxiety-Concentration Factors). In secondary analyses GDS total score was replaced with the three factor scores in repeated models. Balaglitazone Higher GDS score (p=0.03) was significantly associated with lower HV and was marginally related (p=0.06) to FDG hypometabolism. In secondary models higher Dysphoria (p=0.02) and Apathy-Anhedonia (p=0.05) were related to lower HV while higher Apathy-Anhedonia (p=0.003) was the sole factor related to FDG hypometabolism. Amyloid was not a significant predictor in any model. In conclusion very low-level dysphoria apathy and anhedonia may point to neurodegeneration in AD-related regions but this association appears to be independent of amyloid burden. Keywords: Subthreshold depressive symptoms normal cognition Preclinical Alzheimer’s disease biomarkers neurodegeneration INTRODUCTION In cognitively normal (CN) older adults affective symptoms such as depression and apathy predict increased progression to amnestic mild cognitive impairment (MCI) suggesting that these neuropsychiatric symptoms may be very early clinical markers of Alzheimer’s disease (AD) or indicators of other etiopathological processes impacting the Advertisement pathway in the preclinical stage.[1-3] While chronic past due life main depression (LLD) confers the best threat of transition to MCI[3] other styles of Balaglitazone depression such as for example intermittent and remitted main depression[3] or low-grade depressive symptoms measured by depression testing instruments[4] or like a neuropsychiatric Balaglitazone symptom item[1 3 will also be associated with improved threat of Rabbit polyclonal to UBE3A. cognitive decrease in older all those without objective cognitive impairment. Right here the word “subthreshold symptoms Balaglitazone of melancholy” (SSD) can be used to encompass lower intensity depressive classifications that usually do not meet up with diagnostic requirements for major melancholy such as for example subsyndromal melancholy and minor depressive disorder as well as depressive symptoms within a low or subclinical range on depressive disorder scales.[5-9] SSD are common in advancing age and in heterogeneous groups of older adults. Groups of older adults with SSD include those evolving into or remitting from major depressive disorder [10 11 those with a chronic course of SSD that may be accompanied by functional limitations and low perceived social support [11-13] and others who may experience SSD in the context of natural conditions and psychological and physiological processes in very late life.[13] Thus the fate of older individuals with SSD may be varied and disease processes underlying the association of SSD and cognitive decline are not well understood. Cortisol-mediated neurotoxicity within the hippocampus[14-17] and microvascular white matter disease contributing to dysfunction in affective and cognitive control networks[18 19 are two non-AD specific disease mechanisms that have been proposed to underlie the association of LLD and longitudinal cognitive decline that may also be relevant to SSD. It has also been proposed that affective changes such as depressive disorder may be very early symptoms in the AD pathway prior to the stage of MCI that arise from alterations in brain structure and function in regions vulnerable to AD.[1 20 Prior studies have found (syndromal) LLD in CN elderly cohorts to be associated with certain AD biomarkers such as reduced cerebrospinal fluid amyloid-beta 42 [23] entorhinal cortical thinning[24] and hippocampal atrophy including sub-regions of the hippocampus associated with AD-related disease progression. [25 26 Conversely two clinical-pathological studies found that Balaglitazone the association of SSD[21] or full-spectrum depressive symptoms[27] to cognitive decline across CN MCI and dementia stages was unrelated to amyloid plaque burden or neurofibrillary tangle density hallmark pathologies of AD suggesting that other depression-related pathophysiological processes as yet uncharacterized may influence clinical trajectories. Thus far the relations of SSD to in vivo AD-related biomarkers have been largely.