Neuropathological processes associated with dementia of the Alzheimer?s type (AD) begin 15 to 20 years prior to the emergence of clinical symptoms. Biological markers of AD have been identified including measures derived from cerebrospinal fluid and PET scans. However, collection of these measures is prohibitive. There is a dire need to identify ?behavioral biomarkers? of AD that are inexpensive, non-invasive, and widely accessible. To address this need the proposed research examines the utility of a theoretically targeted and novel behavioral biomarker of early stage AD and preclinical AD termed ?memory-based attentional control?, which refers to an attentional control system that is guided by prior experiences (i.e., learning and memory) with stimuli. The measure of memory-based attentional control that this proposal will evaluate is a validated, computerized cognitive task termed the item-specific Stroop task. This task holds promise as a particularly sensitive behavioral biomarker of the earliest stages of AD because: a) it requires coordination of two processes (attentional control and memory) that are sensitive to the earliest stages of AD, b) neural structures that support task performance include the caudate and hippocampus, which are compromised by the earliest stages of AD, and c) preliminary data provide evidence of a breakdown in task performance in the earliest symptomatic stage of AD. The proposed research aims to replicate and expand this work by interrogating the apparent disruption in memory-based attentional control that accompanies early stage AD, including its relationship to targeted brain structures. The research will also explore for the first time the relationship between AD biomarker accumulation and memory-based attentional control in preclinical AD. Knowledge gained from this study may be used to enhance early detection and opportunities for early intervention in AD.
Aim 1 : Examine the utility of memory-based attentional control as a behavioral biomarker by comparing the performance of cognitively healthy older adults with a Clinical Dementia Rating (CDR) of 0 to older adults in the earliest symptomatic stage of AD (CDR .5) on the item-specific Stroop task, and examining relations between task performance and theoretically targeted regional brain volumes (e.g., caudate and hippocampal volume).
Aim 2 : Provide a test of the hypothesis that memory-based attentional control may be sensitive to accumulating AD biomarkers in cognitively healthy older adults (CDR 0) by examining whether individuals with more preclinical AD pathology (i.e., biomarker positive) show greater impairment than those with less AD pathology (i.e., biomarker negative) on the item-specific Stroop task, and examining relations between task performance and theoretically targeted regional brain volumes (e.g., caudate and hippocampal volume).
Neuropathological processes associated with Alzheimer?s disease (AD) begin 15 ? 20 years prior to the emergence of clinical symptoms. There is a need for biomarkers that are inexpensive, non-invasive, and widely accessible, and this R21 proposal addresses this need by examining the utility of a laboratory measure of memory-based attentional control as a behavioral biomarker for the earliest symptomatic stage of AD and preclinical AD. The knowledge gained from this study may be used to enhance early detection and opportunities for early intervention in AD.
