- Email: [email protected]
DONEPEZIL MODULATES PERCEPTUAL LEARNING IN ALZHEIMER’S DISEASE
Poster Presentations: Monday, July 17, 2017
P823
AD group showed less rapid, though demonstrable perceptual learning during the first experimental session, with substantial additional adaptation after taking donepezil. The interaction between group (patient vs controls) and session (pre vs post) was significant, driven by improved performance in the post-donepezil session in the patient group: there was no control ceiling effect. Patients’ performance on standard neuropsychological tasks was not similarly affected by acetylcholinesterase inhibition. There was a significant association between disease severity and strength of improvement on the perceptual learning task. Conclusions: These findings suggest that cholinesterase inhibitors may enhance perceptual learning in AD, particularly for patients with more severe cholinergic deficits. This work has implications for the design of future cognitive rehabilitation strategies and understanding of the neurobiological mechanisms underlying acetylcholinesterase inhibitors.
the Posterior Cingulate Cortex (PCC). Conclusions: Low self-awareness of cognitive deficits is associated with decreased metabolism in the PCC, brain’s implicated in self-referential processing.
P2-477
DONEPEZIL MODULATES PERCEPTUAL LEARNING IN ALZHEIMER’S DISEASE
Chris JD. Hardy1, Yun T. Hwang1, Charles R. Marshall2, Rebecca L. Bond1, Basil H. Ridha2, Sebastian J. Crutch2, Martin N. Rossor2, Jason D. Warren1, 1Institute of Neurology, University College London, London, United Kingdom; 2Dementia Research Centre, Institute of Neurology, University College London, London, United Kingdom. Contact e-mail: c.hardy.12@ ucl.ac.uk Background: Acetylcholinesterase
inhibitors are the mostcommonly prescribed medications for AD, but little information is currently available concerning the impact of these drugs on cognitive domains beyond memory. On neurobiological grounds, one might anticipate a modulatory effect on perceptual learning processes but this has not been established in AD. Here we explored the effect of acetylcholinesterase inhibitors on perceptual learning processes in Alzheimer’s disease (AD). Methods: We assessed the effect of cholinesterase inhibition on auditory perceptual learning using the paradigm of sinewave speech - a classical technique for degrading speech signals (removing spectral detail from speech sounds) that is rapidly and spontaneously compensated by the healthy brain. In a cohort of 15 patients with typical AD, we assessed comprehension of sinewave speech (three digit numbers) pre- and post- a single 10mg dose of donepezil, referenced to repeat sessions in a healthy control group who did not receive donepezil. Results: The healthy control group showed evidence of rapid perceptual learning of sinewave speech across experimental sessions. The
P2-478
DISTINGUISHING NON-AMNESTIC FROM AMNESTIC VARIANTS OF EARLY-ONSET ALZHEIMER’S DISEASE ON NEUROPSYCHOLOGICAL TESTS
Mario F. Mendez1, Lorena Montserratt1, Andrew R. Carr1, Elvira E. Jimenez1, Edmond Teng2, 1University of California at Los Angeles, Los Angeles, CA, USA; 2Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, Los Angeles, CA, USA. Contact e-mail: [email protected] Background: Patients with early-onset Alzheimer’s disease (AD)
include those with typical amnestic AD and those with atypical, non-amnestic presentations, including language, visuospatial, or executive disturbances, who have more focal neocortical localization early in the disease. There are no neuropsychological profiles to distinguish these non-amnestic variants as a group from typical amnestic presentations. Methods: We compared neuropsychological measures of 41 patients meeting AA-NIA criteria for AD and having an age of onset of <65 years of age. Based on the initial extensive physician clinical evaluation, these 41 patients were divided into amnestic (n¼22 including 14 male/8 female; mean years for age-58.4, disease duration-3.2, education-16.1 years) vs. non-amnestic (n¼19 including 8 male/11 female; mean years for age59.7, disease duration-4.0, education-16.2). The two patient groups were of comparable severity on functional measures and had fluorodeoxyglucose positron emission tomography (FDG-PET) or cerebrospinal fluid biomarker confirmation of their disease. We then analyzed neuropsychological differences between these two groups. Results: Six measures emerged as having either sensitivities of 0.8 or specificities of 0.9 for typical amnestic vs. non-amnestic AD (See Table 1). The amnestic EOAD patients were worse on the California Verbal Learning Test (CVLT) delayed recall scores, including “Savings Score” (free long-delayed recall/last
Selected Neuro-psych Tests
Sensitivitya
Specificitya
AUC
T-Test (P-Value)
Forward Digit Span Boston Naming Test Trailmaking B Time CVLT Memory Registration CVLT Recognition False Positives S. California Figure-Ground Test
84.6% 80.0% 37.5% 81.8% 100% 81.1%
45.0% 50.0% 91.7% 42.1% 40.0% 51.0%
0.80** (0.62, 0.98) 0.71 (0.47, 0.94) 0.77* (0.52, 1.00) 0.70 (0.49, 0.91) 0.74* (0.53, 0.94) 0.72* (0.49, 0.96)
0.0019 0.0987 0.0904 0.0798 0.0838 0.0474
*P <.05, **P <.01. a Based on the cutoff values (i.e., 75 percentiles). CVLT ¼ California Verbal Learning Test.
P823
AD group showed less rapid, though demonstrable perceptual learning during the first experimental session, with substantial additional adaptation after taking donepezil. The interaction between group (patient vs controls) and session (pre vs post) was significant, driven by improved performance in the post-donepezil session in the patient group: there was no control ceiling effect. Patients’ performance on standard neuropsychological tasks was not similarly affected by acetylcholinesterase inhibition. There was a significant association between disease severity and strength of improvement on the perceptual learning task. Conclusions: These findings suggest that cholinesterase inhibitors may enhance perceptual learning in AD, particularly for patients with more severe cholinergic deficits. This work has implications for the design of future cognitive rehabilitation strategies and understanding of the neurobiological mechanisms underlying acetylcholinesterase inhibitors.
the Posterior Cingulate Cortex (PCC). Conclusions: Low self-awareness of cognitive deficits is associated with decreased metabolism in the PCC, brain’s implicated in self-referential processing.
P2-477
DONEPEZIL MODULATES PERCEPTUAL LEARNING IN ALZHEIMER’S DISEASE
Chris JD. Hardy1, Yun T. Hwang1, Charles R. Marshall2, Rebecca L. Bond1, Basil H. Ridha2, Sebastian J. Crutch2, Martin N. Rossor2, Jason D. Warren1, 1Institute of Neurology, University College London, London, United Kingdom; 2Dementia Research Centre, Institute of Neurology, University College London, London, United Kingdom. Contact e-mail: c.hardy.12@ ucl.ac.uk Background: Acetylcholinesterase
inhibitors are the mostcommonly prescribed medications for AD, but little information is currently available concerning the impact of these drugs on cognitive domains beyond memory. On neurobiological grounds, one might anticipate a modulatory effect on perceptual learning processes but this has not been established in AD. Here we explored the effect of acetylcholinesterase inhibitors on perceptual learning processes in Alzheimer’s disease (AD). Methods: We assessed the effect of cholinesterase inhibition on auditory perceptual learning using the paradigm of sinewave speech - a classical technique for degrading speech signals (removing spectral detail from speech sounds) that is rapidly and spontaneously compensated by the healthy brain. In a cohort of 15 patients with typical AD, we assessed comprehension of sinewave speech (three digit numbers) pre- and post- a single 10mg dose of donepezil, referenced to repeat sessions in a healthy control group who did not receive donepezil. Results: The healthy control group showed evidence of rapid perceptual learning of sinewave speech across experimental sessions. The
P2-478
DISTINGUISHING NON-AMNESTIC FROM AMNESTIC VARIANTS OF EARLY-ONSET ALZHEIMER’S DISEASE ON NEUROPSYCHOLOGICAL TESTS
Mario F. Mendez1, Lorena Montserratt1, Andrew R. Carr1, Elvira E. Jimenez1, Edmond Teng2, 1University of California at Los Angeles, Los Angeles, CA, USA; 2Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, Los Angeles, CA, USA. Contact e-mail: [email protected] Background: Patients with early-onset Alzheimer’s disease (AD)
include those with typical amnestic AD and those with atypical, non-amnestic presentations, including language, visuospatial, or executive disturbances, who have more focal neocortical localization early in the disease. There are no neuropsychological profiles to distinguish these non-amnestic variants as a group from typical amnestic presentations. Methods: We compared neuropsychological measures of 41 patients meeting AA-NIA criteria for AD and having an age of onset of <65 years of age. Based on the initial extensive physician clinical evaluation, these 41 patients were divided into amnestic (n¼22 including 14 male/8 female; mean years for age-58.4, disease duration-3.2, education-16.1 years) vs. non-amnestic (n¼19 including 8 male/11 female; mean years for age59.7, disease duration-4.0, education-16.2). The two patient groups were of comparable severity on functional measures and had fluorodeoxyglucose positron emission tomography (FDG-PET) or cerebrospinal fluid biomarker confirmation of their disease. We then analyzed neuropsychological differences between these two groups. Results: Six measures emerged as having either sensitivities of 0.8 or specificities of 0.9 for typical amnestic vs. non-amnestic AD (See Table 1). The amnestic EOAD patients were worse on the California Verbal Learning Test (CVLT) delayed recall scores, including “Savings Score” (free long-delayed recall/last
Selected Neuro-psych Tests
Sensitivitya
Specificitya
AUC
T-Test (P-Value)
Forward Digit Span Boston Naming Test Trailmaking B Time CVLT Memory Registration CVLT Recognition False Positives S. California Figure-Ground Test
84.6% 80.0% 37.5% 81.8% 100% 81.1%
45.0% 50.0% 91.7% 42.1% 40.0% 51.0%
0.80** (0.62, 0.98) 0.71 (0.47, 0.94) 0.77* (0.52, 1.00) 0.70 (0.49, 0.91) 0.74* (0.53, 0.94) 0.72* (0.49, 0.96)
0.0019 0.0987 0.0904 0.0798 0.0838 0.0474
*P <.05, **P <.01. a Based on the cutoff values (i.e., 75 percentiles). CVLT ¼ California Verbal Learning Test.