Amyloid-β Imaging in Older Adults Presenting to a Memory Clinic with Subjective Cognitive Decline: A Pilot Study

Subjective complaints about memory and thinking abilities are commonly reported in older adults, with large variation in prevalence estimates (ranging from 25–55% in community-based studies) [1, 2]. Evidence from longitudinal studies indicates complaints confer a degree of elevated risk for subsequent cognitive decline and/or incident dementia/Alzheimer Disease (AD) [3, 4], although there is considerable variability among studies. Reviews also emphasized that determinants of subjective memory complaints (SMCs) in aging are complex and include individual differences in mood and personality [3, 5]. Over the past decade, evidence has accumulated of AD-biomarker associations with subjective memory concerns in otherwise cognitively normal older individuals. Glucose hypometabolism [6, 7], hippocampal atrophy[8, 9], APOE*4 allele status [10, 11], CSF amyloid-beta (Aβ) and tau [12], and amyloid-beta (Aβ) imaging [13, 14] may be linked to subjective memory complaints. Other reports included associations with other neuroimaging biomarkers, such as white matter hyperintensities [15, 16]. Several functional MRI studies demonstrated altered task-related activation [17, 18] or increased [19] / decreased [20] default mode network (DMN) connectivity associated with subjective memory complaints. This line of research is relevant to the NIA-AA proposed staging categories for preclinical AD [21], particularly stage III defined by amyloidosis and early neurodegenerative markers accompanied by subtle cognitive/behavioral decline. This last stage of preclinical AD in the model putatively captures individuals approaching the border zone with clinical criteria for mild cognitive impairment (MCI). As noted in the NIA-AA recommendations on defining preclinical stages of AD [21], subjective memory complaints in otherwise healthy individuals are consistent with the construct of ‘subtle cognitive decline’ [22]. This pilot study reports initial findings on Aβ imaging in patients who have presented to a memory-disorders clinic with cognitive concerns but with normal objective evaluation. Previous studies of subjective memory complaints and Aβ imaging have been inconsistent, with several studies reporting associations [13, 14, 23] and others finding no association [24, 25]. These studies included volunteers completing symptom inventories and self-report measures in a research setting, but otherwise not complaining in a clinically significant context (‘questionnaire-discovered complaints’). The present paper focuses on individuals having sufficient concern about their memory to motivate spontaneous complaint in a clinical setting (‘presenting complainers’). This narrow selection criterion limits generalizability of study findings but is of more direct relevance to the common scenario of the “worried well” in a practice setting [26]. The longer-term study goal is to determine the clinical and prognostic significance of Aβ in subjective cognitive decline (SCD) presenting in this context. In addition to Aβ imaging with Pittsburgh compound B (PiB)-PET, we evaluated subjective cognitive symptoms, depressive symptoms, personality, and performance on more challenging / specific cognitive tasks. In this preliminary report, we hypothesized that clinically presenting SCD individuals will have higher greater Aβ load compared to cognitively normal (CN) older study volunteers.