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69 Evaluation of Ethnoracial Differences in Self- and Study-Partner Reported Subjective Cognitive Decline
- Talia L Robinson, Hannah M Klinger, Rachel F Buckley, Kacie D Deters, Yakeel T Quiroz, Dorene M Rentz, Reisa A Sperling, Rebecca E Amariglio
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 374-375
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Objective:
1) Evaluate the association of self- and study-partner report of subjective cognitive decline (SCD) to objective cognitive performance across ethnoracial groups. 2) Evaluate the concordance of self- and study partner report of SCD across ethnoracial groups.
Participants and Methods:Participants were 5241 non-Hispanic White (NHW), 267 non-Hispanic Black (NHB), 225 Hispanic, and 228 Asian participants screened for the A4 study (N=5961). Participants completed the Preclinical Alzheimer Cognitive Composite (PACC), and self- and study partner-report of SCD using the Cognitive Function Index (CFI). Analysis of variance was used to assess difference in key variables by ethnoracial group. Regression analyses were conducted to evaluate the association of SCD and objective performance by ethnoracial group, and the association between self-and study partner report of SCD by ethnoracial group.
Results:Asian participants reported the highest mean CFI relative to all other groups, while NHW reported the lowest (F(3,5957)=41.93, p <.001). Asian and NHW participants had higher PACC scores relative to NHB and Hispanic participants (F(3,5957)=41.93, p <.001). Regression analyses revealed higher CFI was associated with lower PACC score across groups, and this association was strongest in the Asian sample relative to other groups (F(10, 5897)=40.49, p<.001,R2=.06). Evaluation of study partner characteristics suggested NBH participants had the highest proportion on non-spousal study partners relative to other groups. Regression analyses revealed no differences in the association of self- and study partner report of SCD across ethnoracial groups (F(10, 5859)=132.9, p<.001, R2=0.18).
Conclusions:Results suggest that that SCD is associated with objective cognitive performance across racial groups, although the strength of this association appears to vary in this sample. There is also consistent concordance between self- and study partner report of SCD across groups, despite differences in study partner relationships. SCD may be considered a valid predictor of subtle cognitive change across groups in the A4 sample. Limitations include small group sizes relative to the large NHW sample. Future work with larger, more representative samples are needed to further validate these findings.
13 Regional White Matter Hyperintensities are Associated with Cognition in Prospective Alzheimer’s Clinical Trial Participants
- Clarissa D. Morales, Dejania Cotton-Samuel, Kay C. Igwe, Patrick J. Lao, Julia F. Chang, Amirreza Sedaghat, Mohamad J. Alshikho, Rafael Lippert, Kelsang C. Bista, Kacie Deters, Molly E. Zimmerman, Adam M. Brickman
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 224-225
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Objective:
Previous research established that white matter hyperintensities (WMH), a biomarker of small vessel cerebrovascular disease, are strong predictors of cognitive function in older adults and associated with clinical presentation of Alzheimer’s disease (AD), particularly when distributed in posterior brain regions. Secondary prevention clinical trials, such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, target amyloid accumulation in asymptomatic amyloid positive individuals, but it is unclear the extent to which small vessel cerebrovascular disease accounts for performance on the primary cognitive outcomes in these trials. The purpose of this study was to examine the relationship between regional WMH volume and performance on the Preclinical Alzheimer Cognitive Composite (PACC) among participants screened for participation in the A4 trial. We also determined whether the association between WMH and cognition is moderated by amyloid positivity status.
Participants and Methods:We assessed demographic, amyloid PET status, cognitive screening, and raw MRI data for participants in the A4 trial and quantitated regional (by cerebral lobe) WMH volumes from T2-weighted FLAIR in amyloid positive and amyloid negative participants at screening. Cognition was assessed using PACC scores, a z-score sum of four cognitive tests: The Mini-Mental State Examination (MMSE), the Free and Cued Selective Reminding Test, Logical Memory Test, and Digit Symbol Substitution Test. We included 1329 amyloid positive and 329 amyloid negative individuals (981 women; mean age=71.79 years; mean education=16.58 years) at the time of the analysis. The sample included Latinx (n=50; 3%), non-Latinx (n=1590; 95.9%), or unspecified ethnicity (n=18; 1.1%) individuals who identified as American Indian/Alaskan Native (n=7; 0.4%), Asian (n=38; 2.3%), Black/African American (n=41; 2.5%), White (n=1551 ; 93.5%), or unspecified (n=21; 1.3%) race. We first examined the associations of total and regional WMH volume and amyloid positivity on PACC scores (the primary cognitive outcome measure for A4) using separate general linear models and then determined whether amyloid positivity status and regional WMH statistically interacted for those WMH regions that showed significant main effects.
Results:Both increased WMH, in the frontal and parietal lobes particularly, and amyloid positivity were independently associated with poorer performance on the PACC, with similar magnitude. In subsequent models, WMH volume did not interact with amyloid positivity status on PACC scores.
Conclusions:Regionally distributed WMH are independently associated with cognitive functioning in typical participants enrolled in a secondary prevention clinical trial for AD. These effects are of similar magnitude to the effects of amyloid positivity on cognition, highlighting the extent to which small vessel cerebrovascular disease potentially drives AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered explicitly when evaluating outcomes in trials, both as potential effect modifiers and as possible targets for intervention or prevention. The findings from this study cannot be generalized widely, as the participants are not representative of the overall population.
36 Regional Amyloid and Memory in Amyloid Positive and Negative Older Adults
- Kyla G. Cummings, Clarissa D. Morales, Dejania Cotton-Samuel, Patrick J. Lao, Kacie D. Deters, Molly E. Zimmerman, Adam M. Brickman
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 346-347
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Objective:
Alzheimer’s disease (AD) pathophysiology, including β-amyloid (Aβ), can be appreciated with molecular PET imaging. Among older adults, the distribution of Aβ standard uptake value ratios (SUVR) is typically bimodal and a diagnostic cut is applied to define those who are amyloid ‘positive’ and ‘negative’. However, it is unclear whether the dynamic range of SUVRs in amyloid positive and negative individuals is meaningful and associated with cognition. Previous work by Insel and colleagues (2020) used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) trial to demonstrate subtle associations between a cortical summary SUVR and cognition, particularly on the Free and Cued Selective Reminding Test (FCSRT). We followed up this study to determine the extent to which regional SUVR is associated with performance on the FCSRT in amyloid positive and negative participants screened for participation in the A4 study.
Participants and Methods:We accessed regional Aβ SUVR, including anterior cingulate, posterior cingulate, parietal, precuneus, temporal, and medial/orbital frontal regions, along with FCSRT15 and demographic data from 4492 A4 participants at screening. Participants were coded as amyloid positive (n=1329; 30%) or amyloid negative (n=3169; 70%) based on a summary SUVR of greater than or equal to 1.15. We used separate general linear models to examine the association of total or regional SUVR, amyloid positivity status, and the interaction of SUVR and amyloid status with FCSRT scores. We compared model fits across regions with the Akaike Information Criterion (AIC). We ran post hoc correlational analyses examining the relationship between SUVR and FCSRT scores stratified by amyloid status in the case of significant interactions. Results were similar with and without demographic adjustment.
Results:There was a significant interaction of summary and all regional SUVR with FCSRT scores in addition to main effects of amyloid positivity. In all models, there were small negative associations between SUVR and memory in amyloid positive individuals. For amyloid negative individuals, there was a significant and very small negative association between SUVR and FCSRT scores only in the parietal lobes and precuneus regions. Model fits were generally similar across the different analyses.
Conclusions:In this sample of individuals screened for a secondary prevention trial of AD, there were consistent associations between Aβ SUVR in all regions and memory for those considered amyloid positive. However, for individuals considered amyloid negative, there were only very small associations between SUVR and memory in parietal and precuneus regions. We conclude that the dynamic range of amyloid may be relevant among those with diagnostic evidence of amyloidosis, but that subtle Aβ accumulation in posterior regions may relate to declining memory in “subthreshold” states.