As the population continues to age, the incidence of Alzheimer?s disease (AD) and AD-related dementias (ADRD) is dramatically increasing, resulting in an urgent need to identify at-risk older adults. Effective early identification will occur during the preclinical stages of disease, before the onset of clinically overt symptoms. Subjective cognitive decline (SCD) can represent a preclinical and early disease state that is easily captured in clinical and research settings. SCD is driven by multiple pathological pathways, including AD, neurodegeneration, and cerebral small vessel disease, all of which underlie clinical dementia. Neuropsychiatric symptoms also contribute to SCD and represent early symptoms and a risk for dementia. Current SCD assessment methods lack the specificity to tease apart the underlying etiology of SCD. Tool development has focused on the content of the questions, rather than identifying questions that relate to specific underlying contributors. Additionally, minimal investigation exists understanding the interplay of these mechanisms on the presence of SCD. The majority of research has thus far focused on SCD in relation to a singular pathological process. These approaches to assess definition and tool development limit the specificity of SCD. This study will leverage legacy data from the Vanderbilt Memory & Aging Project, a longitudinal study with a subset of individuals who are cognitively unimpaired and have minimal SCD. To supplement this cohort with an expanded range of SCD and neuropsychiatric symptoms, this proposal will enroll a prospective longitudinal cohort of cognitively unimpaired older adults with a range of SCD. Participants will undergo detailed assessments of cognition, neuroimaging, and lumbar puncture to capture multiple clinical and pathological markers. Leveraging this rich information, the study will shift how SCD items are selected and using feature selection methods will identify questions that relate to each SCD contributor to create profiles that SCD. Modifiers of these profiles will be examined, including age, sex, and concomitant pathologies. The delivery of these novel SCD profiles will enhance the utility of this cost effective and easily measurable early disease marker that can be easily implemented by clinicians and researchers.

Public Health Relevance

Alzheimer?s disease (AD) and AD-related dementias (ADRD) are an increasingly important public health issue with the rapid aging of the population. Early detection of individuals prior to overt or irreversible symptoms is an important step in managing this growing crisis. This preclinical stage represents an ideal time for targeted prevention and therapeutics, when available.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Clinical Neuroscience and Neurodegeneration Study Section (CNN)
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Roberts, Luci
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Vanderbilt University Medical Center
United States
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