Date of Degree

9-2018

Document Type

Dissertation

Degree Name

Ph.D.

Program

Psychology

Advisor

Nancy S. Foldi

Committee Members

Carolyn Pytte

Jennifer Stewart

Adam Brickman

Laura Rabin

Subject Categories

Clinical Psychology | Cognition and Perception

Keywords

Alzheimer Dementia, Cholinesterase Inhibitors, Donepezil, Cognition, Neuropsychiatric Symptoms, Treatment Outcomes

Abstract

Introduction: Cholinesterase Inhibitors (ChEIs) used in Alzheimer’s Disease (AD) have modest effects, heterogeneous treatment response, and it has been difficult to detect treatment response. The standard research and clinical outcome measure, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) aggregates multiple cognitive domains, and has limited sensitivity. We propose that because acetylcholine is directly linked to the cognitive domain of attention, and ChEIs increase available acetylcholine, measures of attention under high-load conditions could predict long-term cognitive, functional and behavioral response, and thus, unlike global measures, could be sensitive to treatment efficacy.

Method: We conducted a longitudinal, open label donepezil trial assessing twenty-three participants with AD at baseline (T1), 6 weeks (T2) and 6 months (T3). Outcome measures were: a) Computerized measures of attention: Foreperiod Effect, Covert Orienting, and Attentional Blink tasks; b) Cognitive: global (ADAS-Cog), memory (Hopkins Verbal Learning Test–Total Recall), executive function (Delis-Kaplan Executive Functioning Scale- Trail Making Test Condition 4); c) Functional: Lawton-Brody Instrumental Activities of Daily Living (IADL); d) Behavioral: Neuropsychiatric Inventory (NPI). Stepwise hierarchical regression analyses were conducted to assess the contribution of different domains, as well as attention change score T2-T1, on ADAS-Cog T3-T1 change score. Linear regressions assessed whether measures of attention at T2 predicted IADL and NPI scores.

Results: Our findings show that attention measures at 6 weeks (T2) could predict 6-month (T3) global cognitive response to treatment better than any other memory or executive measure. Moreover, change in attention performance from baseline to 6 weeks (T2-T1) similarly predicted cognitive performance at 6 months (T3). Finally, performance on attention at 6 weeks (T2) also predicted instrumental activities of daily living and neuropsychiatric symptoms at six months (T3).

Conclusion: Our findings support our hypothesis that measures of attention under high-load conditions are sensitive to donepezil. Performance on these measures predicted long-term cognitive, functional, and behavioral response to ChEIs.

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