P3–036: Attentional psychological refractory period detects early response to donepezil treatment
Year: 2006
Type: article
Study design: Clinical Trial
Abstract: Attentional functions decline in early AD. As animal models demonstrate direct mediation of attention via cholinergic availability, attention measures should detect efficacy of cholinesterase inhibitors in AD. One estimate of attentional resources is the psychological refractory period (PRP), which is the time required to respond to a stimulus and ‘reset’ in order to process a subsequent stimulus. When stimuli follow in rapid succession (< 500 msec), PRP and concomitant reaction times (RT) increase, as resources are allocated to the prior stimulus. To determine: a) sensitivity of attentional PRP relative to other neuropsychological domains, and b) whether changes in PRP capture early treatment efficacy. Fourteen patients with AD undergoing de novo open–label donepezil treatment (mean age=78.9 yrs,±6.8 standard deviation; years education=13.21±3.45; MMSE=22.5±3.48; CDR=0.82±0.24) were evaluated at baseline (T1), after 8.1±2.4 weeks (T2), and 6 months (T3). Change score on ADAS–cognitive (T3–T1) determined group membership of responders (n=9, no change or improved score, mean change=1.98±0.65), and non–responders (n=5, mean change= –5.25±5.0, t(12)=3.89, p=.002). Groups were equated on age, education, disease severity. Measures: A simple detection task was presented at intertrial intervals (ITI) of 500, 800, 1100, 1500msec measured in median RT. Standard neuropsychological tests in domains of attention, language, memory, and visuo–spatial function were converted to z–scores. Neither disease severity nor domain scores showed group differences at T1 or T2, p>.1. The simple detection task showed no Group, Time, or Group × Time effects (p>.1). However, ITI was significant (F(3,36)=15.534, p<.000), showing expected PRP effect at the shortest ITI. Interactions of Group × ITI (Huynh & Feldt F(1.54,36)=3.5, p=.062) and Group × Time × ITI (H&F F(3.0,36)=3.371, p=.029) show that non–responders respond significantly more slowly at 500msec compared to all other ITIs, and further slow response speed after short–term treatment. In contrast, responders maintained their speed from T1 to T2. Attentional PRP was a more sensitive measure of treatment efficacy than standard measures. Despite the groups’ comparable overall speed, non–responders required longer ‘reset’ times than responders implicating poorer attentional resources. After short–term treatment non–responders’ RTs continued to slow, suggesting that they, unlike responders, were failing to respond to cholinergic availability.
Source: Alzheimer s & Dementia
Authors: Nancy S. Foldi, Richard E.C. White, Joel Redfield, Sarah Vedrody, Lillian Kaplan, Kristin I. Lombardi, Jenny Ly
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3021681994