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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.
91 Athletic Status Predicts Neurocognitive Dispersion in College Students
- Eric McConathey, Cara Levitch, Eileen Moran, Molly E Zimmerman
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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. 191-192
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Objective:
Studies have reported that athletic conditioning or training may have neuropsychological benefits for adult athletes, including enhanced processing speed, executive function, and working memory and attention. However, others have reported that these benefits may be attenuated by an athlete’s level of exposure to repetitive, subconcussive head impacts, such as heading the ball in soccer. Neurocognitive dispersion, or intraindividual variability (IIV), has become an increasingly popular tool to assess neuropsychological performance in various clinical populations. Less dispersion is typically associated with more consistent and better overall performance (i.e., fewer lapses of reaction time and accuracy). However, few studies have utilized these measures in healthy young adults. The objective of this study was to determine if athletes and non-athletes exhibited different levels of neurocognitive dispersion on a battery of neuropsychological tasks. It was hypothesized that athletes would exhibit less neurocognitive dispersion compared to non-athletes, despite their exposure to repetitive subconcussive head impacts.
Participants and Methods:Division 1 varsity and club team university athletes (n = 74, Mage = 19.93, female = 55%), and non-athlete undergraduate students (N = 154, Mage = 20.12, female = 69%) completed a neuropsychological battery consisting of 13 cognitive tests. Outcomes for each test were converted to standard scores and combined for overall neuropsychological performance. Two measures of IIV, intraindividual standard deviation (ISD) and maximum discrepancy (MD), were calculated across all 13 cognitive tests for each participant. Intraindividual standard deviation was calculated by taking the standard deviation of the mean performance across each task for each participant. Maximum discrepancy was calculated by subtracted the lowest standard score from the highest standard score per participant across all 13 cognitive tests.
Results:Controlling for the impact of premorbid functioning, depressive symptoms, and gender, an analysis of covariance (ANCOVA) found significantly less ISD in athletes (M = 11.28, SD = 2.76) compared to non-athletes (M = 12.56, SD = 3.61) across all 13 neuropsychological tasks (η2 = 0.04, p = .004). Similarly, significantly lower MD scores were found in athletes (M = 40.25, SD = 11.14) compared to non-athletes (M = 44.69, SD = 14.07) across all 13 neuropsychological tasks (η2 = 0.03, p = .008). Post-hoc analyses revealed no significant differences when athletes were divided into contact and non-contact athletes.
Conclusions:Similar to prior findings that aerobic exercise may enhance cognitive performance, both contact and non-contact college athletes exhibited less neurocognitive dispersion (as measured by ISD and MD) compared to non-athlete college students. However, no significant differences were found between non-contact athletes and contact athletes (soccer players) who were exposed to repetitive subconcussive heading events. These findings suggest that athletic performance in college-aged athletes may lead to more consistent and therefore overall better neuropsychological performance despite exposure to repetitive subconcussive head impacts.
77 Symptoms of RBD and Cognitive Performance in Healthy Young Adults
- Theresa Lin, Eileen Moran, Molly E Zimmerman
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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. 585-586
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Objective:
REM sleep behavior disorder (RBD) is a parasomnia characterized by vivid dreams and motor behavior such that people appear to “act out their dreams.” These are sudden and often violent bodily movements such as punching or kicking, or vocalizations such as laughing or shouting. RBD is mostly associated with the older adult male population. However, recent studies show that RBD and REM sleep without atonia (RSWA) also occur in other populations, including women, children, and adolescents. Given the prodromal period before an individual can develop the classic symptoms of RBD and that RBD is not just limited to older adult males, it is important to study subclinical features of RBD. RBD is a parasomnia and poor sleep is well known to affect cognitive domains. Additionally, RBD is separately shown to negatively affect cognition in older adults. Given these connections, the association between RBD symptoms and cognition among young adults warrants further study. The purpose of this study was to evaluate the association between RBD symptoms and cognitive domains, specifically attention, processing speed, executive function, and working memory.
Participants and Methods:University students from the Bronx, NY (N=50, mean age = 19.8, female = 78.4%) completed the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ). Estimated intellectual ability was assessed using the Wechsler Test of Adult Reading (WTAR). Cognitive assessment included the Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test (attention and executive function) and the Cogstate battery (Groton Maze Learning Test (executive function), Chase Test (processing speed), Identification Test (attention), One Back Test (attention), and Two Back Test (working memory)). Psychosocial assessment included the Perceived Stress Scale (PSS), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI).
Results:A series of general linear models were used to determine the relationship between RBD symptoms and cognition. Race/ethnicity, depressive symptoms, and estimated intellectual ability were included as covariates. Using a cutoff score of five (range: 0-13) on the RBDSQ, the ANCOVAs determined that there was no association between RBD symptoms and the cognitive domains of attention, processing speed, executive function, and working memory. However, there was a trend for attention as measured by the Identification task (F(1,41) = 3.85, p = 0.057). Interestingly, Pearson’s chi-square test revealed that the relationship between depressive symptoms and RBD symptoms was significant (x2 = 6.87, p = 0.009). Those who had high RBD symptoms were more likely to have high depressive symptoms.
Conclusions:Our analyses indicated that in healthy young adults, RBD symptoms are not associated with the cognitive domains of attention, processing speed, executive function, or working memory. However, there may be a trend for attention, which warrants further research with a larger sample size. Of interest, young adults with RBD symptoms were more likely to have clinically significant depressive symptoms. Given that RBD in older adults is associated with incident dementia with Lewy body and Parkinson’s disease, which are associated with cognitive decline and depression, further work is necessary to explore the mechanisms of this connection as well as the development of clinical disorders.
The Impact of Sleep on the Relationship between Soccer Heading Exposure and Neuropsychological Function in College-Age Soccer Players
- Cara F. Levitch, Eric McConathey, Maral Aghvinian, Mark Himmelstein, Michael L. Lipton, Molly E. Zimmerman
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- Journal of the International Neuropsychological Society / Volume 26 / Issue 7 / August 2020
- Published online by Cambridge University Press:
- 26 February 2020, pp. 633-644
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Objective:
Soccer is the most popular sport worldwide and is the only sport where athletes purposely use their head to deflect the ball during play, termed “heading” the ball. These repetitive head impacts (RHI) are associated with worse neuropsychological function; however, factors that can increase risk of injury following exposure to such head impacts have been largely unexamined. The present study provided a novel examination of the modifying role of sleep on the relationship between RHI exposure and neuropsychological function in college-age soccer players.
Methods:Fifty varsity and intramural college soccer players completed questionnaires assessing recent and long-term heading exposure, a self-report measure of sleep function, and a battery of neuropsychological tests.
Results:A high level of recent heading exposure was significantly associated with poorer processing speed, independent of concussion history. With reduced sleep duration, a high level of recent heading exposure was related to worse sustained attention. However, with greater hours of sleep duration, heading exposure was related to preserved neuropsychological outcome in sustained attention.
Conclusions:We replicated our earlier finding of an association between recent head impact exposure and worse processing speed in an independent sample. In addition, we found that sleep may serve as a risk or protective factor for soccer players following extensive exposure to head impacts. Ultimately, this study furthers the understanding of factors impacting neuropsychological function in soccer players and provides empirical support for sleep interventions to help ensure safer soccer play and recovery from injury.
Neuropsychological Function Response to Nocturnal Blue Light Blockage in Individuals With Symptoms of Insomnia: A Pilot Randomized Controlled Study
- Molly E. Zimmerman, Moosun Brad Kim, Christiane Hale, Andrew J. Westwood, Adam M. Brickman, Ari Shechter
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- Journal of the International Neuropsychological Society / Volume 25 / Issue 7 / August 2019
- Published online by Cambridge University Press:
- 20 March 2019, pp. 668-677
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Objectives: Insomnia is associated with neuropsychological dysfunction. Evidence points to the role of nocturnal light exposure in disrupted sleep patterns, particularly blue light emitted through smartphones and computers used before bedtime. This study aimed to test whether blocking nocturnal blue light improves neuropsychological function in individuals with insomnia symptoms. Methods: This study used a randomized, placebo-controlled crossover design. Participants were randomly assigned to a 1-week intervention with amber lenses worn in wrap-around frames (to block blue light) or a 1-week intervention with clear lenses (control) and switched conditions after a 4-week washout period. Neuropsychological function was evaluated with tests from the NIH Toolbox Cognition Battery at three time points: (1) baseline (BL), (2) following the amber lenses intervention, and (3) following the clear lenses intervention. Within-subjects general linear models contrasted neuropsychological test performance following the amber lenses and clear lenses conditions with BL performance. Results: Fourteen participants (mean(standard deviation, SD): age = 46.5(11.4)) with symptoms of insomnia completed the protocol. Compared with BL, individuals performed better on the List Sorting Working Memory task after the amber lenses intervention, but similarly after the clear lenses intervention (F = 5.16; p = .014; η2 = 0.301). A similar pattern emerged on the Pattern Comparison Processing Speed test (F = 7.65; p = 0.002; η2 = 0.370). Consideration of intellectual ability indicated that treatment with amber lenses “normalized” performance on each test from approximately 1 SD below expected performance to expected performance. Conclusions: Using a randomized, placebo-controlled crossover design, we demonstrated improvement in processing speed and working memory with a nocturnal blue light blocking intervention among individuals with insomnia symptoms. (JINS, 2019, 25, 668–677)
Recent and Long-Term Soccer Heading Exposure Is Differentially Associated With Neuropsychological Function in Amateur Players
- Cara F. Levitch, Molly E. Zimmerman, Naomi Lubin, Namhee Kim, Richard B. Lipton, Walter F. Stewart, Mimi Kim, Michael L. Lipton
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- Journal of the International Neuropsychological Society / Volume 24 / Issue 2 / February 2018
- Published online by Cambridge University Press:
- 22 August 2017, pp. 147-155
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Objectives: The present study examined the relative contribution of recent or long-term heading to neuropsychological function in amateur adult soccer players. Participants and Methods: Soccer players completed a baseline questionnaire (HeadCount-12m) to ascertain heading during the prior 12 months (long-term heading, LTH) and an online questionnaire (HeadCount-2w) every 3 months to ascertain heading during the prior 2 weeks (recent heading, RH). Cogstate, a battery of six neuropsychological tests, was administered to assess neuropsychological function. Generalized estimating equations were used to test if LTH or RH was associated with neuropsychological function while accounting for the role of recognized concussion. Results: A total of 311 soccer players completed 630 HeadCount-2w. Participants had an average age of 26 years. Participants headed the ball a median of 611 times/year (mean=1,384.03) and 9.50 times/2 weeks (mean=34.17). High levels of RH were significantly associated with reduced performance on a task of psychomotor speed (p=.02), while high levels of LTH were significantly associated with poorer performance on tasks of verbal learning (p=.03) and verbal memory (p=.04). Significantly better attention (p=.02) was detectable at moderately high levels of RH, but not at the highest level of RH. One hundred and seven (34.4%) participants reported a lifetime history of concussion, but this was not related to neuropsychological function and did not modify the association of RH or LTH with neuropsychological function. Conclusion: High levels of both RH and LTH were associated with poorer neuropsychological function, but on different domains. The clinical manifestations following repetitive exposure to heading could change with chronicity of exposure. (JINS, 2018, 24, 147–155)
Sleep Onset/Maintenance Difficulties and Cognitive Function in Nondemented Older Adults: The Role of Cognitive Reserve
- Molly E. Zimmerman, Marcelo E. Bigal, Mindy J. Katz, Adam M. Brickman, Richard B. Lipton
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- Journal of the International Neuropsychological Society / Volume 18 / Issue 3 / May 2012
- Published online by Cambridge University Press:
- 09 February 2012, pp. 461-470
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This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects. The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based cohort. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower: ⩽12 years; higher: >12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates. Participants were an average age of 79.7 ± 5.0 years (range = 71–97 years). Fifty-seven percent (n = 314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0; p < .001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD × education interaction (F(1,536) = 14.5; p = .00)). Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency. (JINS, 2012, 18, 461–470)
Level of Recall, Retrieval Speed, and Variability on the Cued-Recall Retrieval Speed Task (CRRST) in Individuals with Amnestic Mild Cognitive Impairment
- Wendy S. Ramratan, Laura A. Rabin, Cuiling Wang, Molly E. Zimmerman, Mindy J. Katz, Richard B. Lipton, Herman Buschke
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- Journal of the International Neuropsychological Society / Volume 18 / Issue 2 / March 2012
- Published online by Cambridge University Press:
- 23 January 2012, pp. 260-268
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Individuals with amnestic mild cognitive impairment (aMCI) show deficits on traditional episodic memory tasks and reductions in speed of performance on reaction time tasks. We present results on a novel task, the Cued-Recall Retrieval Speed Task (CRRST), designed to simultaneously measure level and speed of retrieval. A total of 390 older adults (mean age, 80.2 years), learned 16 words based on corresponding categorical cues. In the retrieval phase, we measured accuracy (% correct) and retrieval speed/reaction time (RT; time from cue presentation to voice onset of a correct response) across 6 trials. Compared to healthy elderly adults (HEA, n = 303), those with aMCI (n = 87) exhibited poorer performance in retrieval speed (difference = −0.13; p < .0001) and accuracy on the first trial (difference = −0.19; p < .0001), and their rate of improvement in retrieval speed was slower over subsequent trials. Those with aMCI also had greater within-person variability in processing speed (variance ratio = 1.22; p = .0098) and greater between-person variability in accuracy (variance ratio = 2.08; p = .0001) relative to HEA. Results are discussed in relation to the possibility that computer-based measures of cued-learning and processing speed variability may facilitate early detection of dementia in at-risk older adults. (JINS, 2012, 18, 260–268)