INS NYC 2024 Program

Poster	Poster Session 04 Program Schedule 02/15/2024 12:00 pm - 01:15 pm Room: Majestic Complex (Posters 61-120) Poster Session 04: Neuroimaging \| Neurostimulation/Neuromodulation \| Teleneuropsychology/Technology Final Abstract #104 Latent Class Mixed Models Reveal Lower Locus Coeruleus Integrity is Associated with Diminished Practice Effect Response Times in Clinically Unimpaired Older Individuals Lindsay Smegal, Department of Psychology, Georgia State University, Atlanta, United States Christoph Schneider, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, United States Roos Jutten, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, United States Rory Boyle, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, United States Dorene Rentz, Department of Neurology, Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, Boston, United States Keith Johnson, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, United States Reisa Sperling, Department of Neurology, Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, Boston, United States Kathryn Papp, Department of Neurology, Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, Boston, United States Heidi Jacobs, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, United States Category: Dementia (Alzheimer's Disease) Keyword 1: computerized neuropsychological testing Keyword 2: neuroimaging: structural Keyword 3: dementia - Alzheimer's disease Objective: The locus coeruleus (LC) modulates learning and is one of the first regions of hyperphosphorylated tau aggregation in Alzheimer’s disease (AD). Practice effects (PE) are used to detect subtle cognitive changes in preclinical AD, where diminished PE have been associated with greater amyloid burden, tau deposition in the entorhinal cortex, and cognitive decline. Using a data-driven approach, we assessed the relationship between LC integrity and PE. Participants and Methods: Seventy-six clinically unimpaired participants from the Harvard Aging Brain Study (age=77.1±4.8yrs, 62% female, MMSE=29±1.3) completed an at-home computerized face-name letter task (FNLT) and a behavioral pattern separation task (BPSO) monthly over one year. The same version of the FNLT, a delayed recall task, was presented each month, while four versions of the BPSO were alternated each month (A-B-C-D-A-B-C-D-etc.). Participants underwent 3T LC-imaging and PET imaging within one year of baseline. Linear latent class mixed models with spline-based link functions identified two and three classes of time-varying trajectories for FNLT and BPSO accuracy scores and response times (RTs), correcting for baseline age, sex, and years of education. Models with classes N≥5 were evaluated with AIC, BIC, entropy, and ICL. The classes in each model were compared using Kruskal-Wallis tests for the following baseline characteristics: Clinical Dementia Rating Scale, neocortical ¹¹C-Pittsburg Compound-B distribution volume ratio, MMSE, Preclinical Alzheimer’s Cognitive Composite-5 (PACC-5), LC integrity, entorhinal cortex ¹⁸F-Flortaucipir (FTP) standardized uptake value ratio (SUVR), inferior temporal FTP SUVR, and amygdala FTP SUVR. Further group analyses identified baseline differences between the common best and worst learners in terms of RTs and accuracy scores. Participants who learned best over time in both tasks were grouped as “strong”, those who were consistently in the worst class as “weak”, and the remaining as “medium”. Results: A three-class FNLT RT model revealed the group with the slowest RTs across one year had lower LC integrity (p=0.029), and higher entorhinal and amygdala tau burden (p=0.016; p=0.028). A two-class BPSO RT model did not yield significant differences between classes. Overlapping classes based on FNLT and BPSO RT showed a dose-response-like relationship: the “weak” PE RT group exhibiting lowest LC integrity and highest entorhinal tau, and the “medium” and “strong” groups exhibiting gradually higher LC integrity (p=0.007) and lower entorhinal tau (p=0.017). A two-class FNLT accuracy score model revealed the group with diminished PE over one year had lower PACC-5 (p=0.003) and MMSE (p=0.02) scores. Similarly, a two-class BPSO accuracy score model revealed those with diminished PE over one year had lower PACC-5 (p=0.034). Overlapping classes based on FNLT and BPSO accuracy scores showed a dose-response-like relationship: the “weak” PE group exhibiting worst PACC-5 performance, and the “medium” and “strong” groups exhibiting gradually higher PACC-5 performance (p<0.001). Conclusions: These findings suggest PE measured using monthly RTs may be a sensitive measure for early biomarkers such as LC integrity and tau burden, where lower LC integrity and greater entorhinal tau burden are associated with slower RT. Further research should elucidate how these findings relate to longitudinal accumulation in AD pathology and cognitive decline.

Poster

02/15/2024
12:00 pm - 01:15 pm
Room: Majestic Complex (Posters 61-120)

Poster Session 04: Neuroimaging | Neurostimulation/Neuromodulation | Teleneuropsychology/Technology

Final Abstract #104

Latent Class Mixed Models Reveal Lower Locus Coeruleus Integrity is Associated with Diminished Practice Effect Response Times in Clinically Unimpaired Older Individuals

Lindsay Smegal, Department of Psychology, Georgia State University, Atlanta, United States
Christoph Schneider, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Roos Jutten, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Rory Boyle, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Dorene Rentz, Department of Neurology, Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, Boston, United States
Keith Johnson, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, United States
Reisa Sperling, Department of Neurology, Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, Boston, United States
Kathryn Papp, Department of Neurology, Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, Boston, United States
Heidi Jacobs, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: computerized neuropsychological testing
Keyword 2: neuroimaging: structural
Keyword 3: dementia - Alzheimer's disease

Objective:

The locus coeruleus (LC) modulates learning and is one of the first regions of hyperphosphorylated tau aggregation in Alzheimer’s disease (AD). Practice effects (PE) are used to detect subtle cognitive changes in preclinical AD, where diminished PE have been associated with greater amyloid burden, tau deposition in the entorhinal cortex, and cognitive decline. Using a data-driven approach, we assessed the relationship between LC integrity and PE.

Participants and Methods:

Seventy-six clinically unimpaired participants from the Harvard Aging Brain Study (age=77.1±4.8yrs, 62% female, MMSE=29±1.3) completed an at-home computerized face-name letter task (FNLT) and a behavioral pattern separation task (BPSO) monthly over one year. The same version of the FNLT, a delayed recall task, was presented each month, while four versions of the BPSO were alternated each month (A-B-C-D-A-B-C-D-etc.). Participants underwent 3T LC-imaging and PET imaging within one year of baseline. Linear latent class mixed models with spline-based link functions identified two and three classes of time-varying trajectories for FNLT and BPSO accuracy scores and response times (RTs), correcting for baseline age, sex, and years of education. Models with classes N≥5 were evaluated with AIC, BIC, entropy, and ICL. The classes in each model were compared using Kruskal-Wallis tests for the following baseline characteristics: Clinical Dementia Rating Scale, neocortical ¹¹C-Pittsburg Compound-B distribution volume ratio, MMSE, Preclinical Alzheimer’s Cognitive Composite-5 (PACC-5), LC integrity, entorhinal cortex ¹⁸F-Flortaucipir (FTP) standardized uptake value ratio (SUVR), inferior temporal FTP SUVR, and amygdala FTP SUVR. Further group analyses identified baseline differences between the common best and worst learners in terms of RTs and accuracy scores. Participants who learned best over time in both tasks were grouped as “strong”, those who were consistently in the worst class as “weak”, and the remaining as “medium”.

Results:

A three-class FNLT RT model revealed the group with the slowest RTs across one year had lower LC integrity (p=0.029), and higher entorhinal and amygdala tau burden (p=0.016; p=0.028). A two-class BPSO RT model did not yield significant differences between classes. Overlapping classes based on FNLT and BPSO RT showed a dose-response-like relationship: the “weak” PE RT group exhibiting lowest LC integrity and highest entorhinal tau, and the “medium” and “strong” groups exhibiting gradually higher LC integrity (p=0.007) and lower entorhinal tau (p=0.017). A two-class FNLT accuracy score model revealed the group with diminished PE over one year had lower PACC-5 (p=0.003) and MMSE (p=0.02) scores. Similarly, a two-class BPSO accuracy score model revealed those with diminished PE over one year had lower PACC-5 (p=0.034). Overlapping classes based on FNLT and BPSO accuracy scores showed a dose-response-like relationship: the “weak” PE group exhibiting worst PACC-5 performance, and the “medium” and “strong” groups exhibiting gradually higher PACC-5 performance (p<0.001).

Conclusions:

These findings suggest PE measured using monthly RTs may be a sensitive measure for early biomarkers such as LC integrity and tau burden, where lower LC integrity and greater entorhinal tau burden are associated with slower RT. Further research should elucidate how these findings relate to longitudinal accumulation in AD pathology and cognitive decline.