17 results
2 Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes
- Kelsey R Thomas, Katherine J Bangen, Alexandra J Weigand, Gema Ortiz, Kayla S Walker, David P Salmon, Mark W Bondi, Emily C Edmonds
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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. 103-104
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Objective:
There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer’s disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults. We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of <129 across subgroups.
Participants and Methods:A hierarchical cluster analysis was conducted using 11 baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (age M=71.93 years, SD=7.51; 55.9% women; 15.6% Hispanic/Latino/a/x/e). A discriminate function analysis was then conducted to test whether the individual neuropsychological scores predicted cluster-group membership. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score <129, by cluster group.
Results:Cluster analysis identified 5 groups: All-Average (n=139), Low-Visuospatial (n=46), Low-Executive (n=51), Low-Memory/Language (n=83), and Low-All Domains (n=46). The discriminant function analysis using the neuropsychological measures to predict group membership into these 5 clusters correctly classified 85.2% of the participants. Subgroups had unique demographic and clinical characteristics. Relative to the All-Average group, the Low-Visuospatial (hazard ratio [HR] 2.39, 95% CI [1.03, 5.56], p=.044), Low-Memory/Language (HR 4.37, 95% CI [2.24, 8.51], p<.001), and Low-All Domains (HR 7.21, 95% CI [3.59, 14.48], p<.001) groups had greater risk of progression to MCI/dementia. The Low-Executive group was also twice as likely to progress to MCI/dementia compared to the AllAverage group, but did not statistically differ (HR 2.03, 95% CI [0.88,4.70], p=.096). A similar pattern of results was found for progression to DRS score <129, with the Low-Executive (HR 2.82, 95% CI [1.26, 6.29], p=.012), Low-Memory/Language (HR 3.70, 95% CI [1.80, 7.56], p<.001) and Low-All Domains (HR 5.79, 95% CI [2.74, 12.27], p<.001) groups at greater risk of progression to a DRS score <129 than the All-Average group. The Low-Visuospatial group was also twice as likely to progress to DRS <129 compared to the All-Average group, but did not statistically differ (HR 2.02, 95% CI [0.80, 5.06], p=.135).
Conclusions:Our results add to a growing literature documenting heterogeneity in the earliest cognitive and pathological presentations associated with Alzheimer’s disease and related disorders. Participants with subtle memory/language, executive, and visuospatial weaknesses all declined at faster rates than the All-Average group, suggesting that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. These results have important implications for early identification of individuals at risk for MCI/dementia. Given that the same classification approach may not be optimal for everyone, determining profiles of subtle cognitive difficulties in CU individuals and implementing neuropsychological test batteries that assess multiple cognitive domains may be a key step towards an individualized approach to early detection and fewer missed opportunities for early intervention.
6 Pulse Pressure and APOE ε4 Dose Interact to Affect Cerebral Blood Flow in Older Adults Without Dementia
- Lauren Edwards, Kelsey R Thomas, Alexandra J Weigand, Emily C Edmonds, Alexandra L Clark, Einat K Brenner, Daniel A Nation, Lisa Delano-Wood, Mark W Bondi, Katherine J Bangen
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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. 107-108
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Objective:
Alterations in cerebral blood flow (CBF) are associated with risk of cognitive decline and Alzheimer’s disease (AD). Although apolipoprotein E (APOE) ε4 and greater vascular risk burden have both been linked to reduced CBF in older adults, less is known about how APOE ε4 status and vascular risk may interact to influence CBF. We aimed to determine whether the effect of vascular risk on CBF varies by gene dose of APOE ε4 alleles (i.e., number of e4 alleles) in older adults without dementia.
Participants and Methods:144 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent arterial spin labeling (ASL) and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure assessment. Vascular risk was assessed using pulse pressure (systolic blood pressure -diastolic blood pressure), which is thought to be a proxy for arterial stiffening. Participants were classified by number of APOE ε4 alleles (n0 alleles = 87, m allele = 46, n2 alleles = 11). CBF in six FreeSurfer-derived a priori regions of interest (ROIs) vulnerable to AD were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regression models tested the interaction between categorical APOE ε4 dose (0, 1, or 2 alleles) and continuous pulse pressure on CBF in each ROI, adjusting for age, sex, cognitive diagnosis (cognitively unimpaired vs. mild cognitive impairment), antihypertensive medication use, cerebral metabolism (FDG-PET composite), reference CBF region (precentral gyrus), and AD biomarker positivity defined using the ADNI-optimized phosphorylated tau/ß-amyloid ratio cut-off of > 0.0251 pg/ml.
Results:A significant pulse pressure X APOE ε4 dose interaction was found on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex (ps < .005). Among participants with two e4 alleles, higher pulse pressure was significantly associated with lower CBF (ps < .001). However, among participants with zero or one ε4 allele, there was no significant association between pulse pressure and CBF (ps > .234). No significant pulse pressure X APOE ε4 dose interaction was found in the inferior temporal cortex, rostral middle frontal gyrus, or medial orbitofrontal cortex (ps > .109). Results remained unchanged when additionally controlling for general vascular risk assessed via the modified Hachinski Ischemic Scale.
Conclusions:These findings demonstrate that the cross-sectional association between pulse pressure and region-specific CBF differs by APOE ε4 dose. In particular, a detrimental effect of elevated pulse pressure on CBF in AD-vulnerable regions was found only among participants with the e4/e4 genotype. Our findings suggest that pulse pressure may play a mechanistic role in neurovascular unit dysregulation for those genetically at greater risk for AD. Given that pulse pressure is just one of many potentially modifiable vascular risk factors for AD, future studies should seek to examine how these other factors (e.g., diabetes, high cholesterol) may interact with APOE genotype to affect cerebrovascular dysfunction.
17 Education Moderates the Association Between Hippocampal CBF and Memory in Women but Not Men
- Einat K Brenner, Alexandra J Weigand, Lauren C Edwards, Amanda T Calcetas, Maria Bordyug, Sarah J Banks, Erin E Sundermann, Kelsey R Thomas, Mark W Bondi, Katherine J Bangen
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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. 227-228
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Objective:
Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.
Participants and Methods:Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.
Results:CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.
Conclusions:These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.
1 Associations between social determinants of health and 10-year change in everyday functioning within Black and White older adults from the ACTIVE study
- Alexandra L. Clark, Alexandra J. Weigand, Olivio J. Clay, Michael Marsiske, Joshua Owens, Jacob Fiala, Michael Crowe, Kelsey R. Thomas
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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. 783-784
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Objective:
Social determinants of health (SDoH) are structural elements of our living and working environments that fundamentally shape health risks and outcomes. The Healthy People 2030 campaign delineated SDoH into five distinct categories that include: economic stability, education access/quality, healthcare access, neighborhood and built environment, and social and community contexts. Recent research has demonstrated that minoritized individuals have greater disadvantage across SDoH domains, which has been linked to poorer cognitive performance in older adulthood. However, the independent effects of SDoH on everyday functioning across and within racial groups remains less clear. The current project explored the association between SDoH factors and 10-year change in everyday functioning in a large sample of community-dwelling Black and White older adults.
Participants and Methods:Data from 2,505 participants without dementia enrolled in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (age M=73.5; 76% women; 28% Black/African American). Sociodemographic, census, and industry classification data were reduced into five SDoH factors: economic stability, education access and quality, healthcare access and quality, neighborhood and built environment, and social and community contexts. The Observed Tasks of Daily Living, a performance-based measure of everyday functioning with tasks involving medication management, finances, and telephone use, was administered at baseline, 1-, 2-, 3-, 5, and 10-year follow up visits. Mixed-effects models with age as the timescale tested (1) racial group differences in OTDL trajectories, (2) race x SDOH interactions on OTDL trajectories, and (3) associations between SDoH and OTDL trajectories stratified within Black and White older adults. Covariates included sex/gender, vocabulary score, Mini-Mental Status Examination, depressive symptoms, visual acuity, general health, training group status, booster status, testing site, and recruitment wave.
Results:Black older adults had a steeper decline of OTDL performance compared to Whites (linear: b = -.25, quadratic b=-.009, ps < .001). There was a significant race x social and community context interaction on linear OTDL trajectories (b =.06, p=.01), but no other significant race x SDoH interactions were observed (bs =-.007-.05, ps=.73-.11). Stratified analyses revealed lower levels of social and community context were associated with steeper age-related linear declines in OTDL performance in Black (b = .08, p=.001), but not White older adults (b =.004, p=.64). Additionally, lower levels of economic stability were associated with steeper age-related linear declines in OTDL performance in Black (b =.07, p=.04), but not White older adults (b =.01, p=.35). Finally, no significant associations between other SDoH and OTDL trajectories were observed in Black (bs = -.04-.01, ps =.09-.80) or White (bs = -.02-.003, ps=.07-.96) older adults.
Conclusions:SDoH, which measure aspects of structural racism, play an important role in accelerating age-related declines in everyday functioning. Lower levels of economic and community-level social resources are two distinct SDoH domains associated with declines in daily functioning that negatively impact Black, but not White, older adults. It is imperative that future efforts focus on both identifying and acting upon upstream drivers of SDoH-related inequities. Within the United States, this will require addressing more than a century of antiBlack sentiment, White supremacy, and unjust systems of power and policies designed to intentionally disadvantage minoritized groups.
3 Type 2 Diabetes Moderates the Association between Amyloid PET and Attention/Executive Functioning in Older Veterans
- Rachel Membreno Almendares, Katherine J Bangen, Monica T Ly, Kayla S Walker, Sunder Mudaliar, Kelsey R Thomas
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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. 104-105
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Objective:
Type 2 diabetes (T2D) is a risk factor for cognitive impairment/dementia and has been shown to modify the impact of Alzheimer’s disease (AD) biomarkers on cognition and everyday functioning. Studies examining amyloid-ß (Aß), one of the hallmark AD pathologies, have shown mixed results regarding associations of Aß biomarkers with cross-sectional cognition as well as T2D, though Aß is generally associated with future cognitive declines. The purpose of the present study is to examine whether T2D impacts the associations between amyloid positron emission tomography (PET) and cognition in older Veterans.
Participants and Methods:The current study included 202 mostly male Vietnam-Era Veterans from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DOD ADNI) study (age M=69.38 years, SD=4.37; 40% with self-reported T2D) who completed neuropsychological testing and florbetapir PET imaging. The Aß PET standardized uptake variable ratio (SUVR) was measured using a previously-validated summary SUVR calculated by dividing the mean uptake across 4 AD-vulnerable cortical regions by whole cerebellar uptake. General linear models examined whether T2D moderated the relationship of Aß PET with memory, attention/executive functioning, and language composite scores. Models adjusted for age, education, apolipoprotein E e4 carrier status, vascular risk burden, depressive symptoms, post-traumatic stress disorder (PTSD) symptom severity, and history of traumatic brain injury (TBI).
Results:There was no main effect of diabetes on memory, attention/executive functioning, or language performance, and higher Aß PET SUVR was only associated with worse attention/executive functioning performance (ß=-.146, 95% CI [-.261, -.031], p=.013). The Aß PET x T2D interaction was significant for attention/executive functioning such that higher Aß PET SUVR was associated with lower attention/executive functioning scores, but only in those with T2D (ß=-.116, [-.225, -.006], p=.038). This interaction was not significant for language or memory.
Conclusions:The results show that Aß may negatively impact attention/executive functioning, but this effect was only found in Veterans with T2D. Prior work has suggested that T2D may be more associated with tau biomarkers than markers of Aß, so it is possible that the current results are due to a compounding effect of Aß pathology plus microvascular and/or tau pathology. Notably, the sample was relatively young, a relatively large proportion had elevated PTSD symptoms and/or a TBI history (which have both been shown to relate to attention/executive function), and the measures that made up the attention/executive composite (Trail Making Test A and B) have been shown to be particularly sensitive - all of which may have contributed to the domain-specific effects. Future research is needed to investigate the role that tau and vascular pathology may play in cognition among individuals with T2D. Longitudinal studies are also needed to better understand the timing and progression of these relationships.
56 TBI Severity Moderates the Association between Subjective and Objective Attention in Older Veterans
- Peter P Rantins, Monica Ly, Alexandra L Clark, Alexandra J Weigand, Kayla S Walker, Victoria C Merritt, Katherine J Bangen, Kelsey R Thomas
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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. 363-364
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Objective:
Prior work on associations between self-reported cognition and objective cognitive performance in Veterans has yielded mixed findings, with some evidence indicating that mild traumatic brain injury (TBI) may not impact the associations between subjective and objective cognition. However, few studies have examined these relationships in both mild and moderate-to-severe TBI, in older Veterans, and within specific cognitive domains. Therefore, we assessed the moderating effect of TBI severity on subjective and objective cognition across multiple cognitive domains.
Participants and Methods:This study included 246 predominately male Vietnam-Era Veterans (age M=69.61, SD=4.18, Range = 60.87 – 85.16) who completed neuropsychological testing and symptom questionnaires as part of the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI). Participants were classified as having history of no TBI (n=81), mild TBI (n=80), or moderate-tosevere TBI (n=85). Neuropsychological composite scores in the domains of memory, attention/executive functioning, and language were included as the outcome variables. The Everyday Cognition (ECog) measure was used to capture subjective cognition and, specifically, the ECog domain scores of memory, divided attention, and language were chosen as independent variables to mirror the objective cognitive domains. General linear models, adjusting for age, education, apolipoprotein E ε4 carrier status, pulse pressure, depressive symptom severity, and PTSD symptom severity, tested whether TBI severity moderated the associations of domain-specific subjective and objective cognition.
Results:Across the sample, subjective memory was associated with objective memory (β=-.205, 95% CI [-.332, -.078], p=.002) and subjective language was associated with objective language (β=-.267, 95% CI [-.399, -.134], p<.001). However, the main effect of subjective divided attention was not associated with objective attention/executive functioning (p=.124). The main effect of TBI severity was not associated with any of the objective cognitive domain scores after adjusting for the other variables in the model. The TBI severity x subjective cognition interaction was significant for attention/executive functioning [F(2,234)=5.18, p=.006]. Specifically, relative to Veterans without a TBI, participants with mild TBI (β=-.311, 95% CI [-.620, -.002], p=.048) and moderate-to-severe TBI (β=-.499, 95% CI [-.806, -.193], p=.002) showed stronger negative associations between subjective divided attention and objective attention/executive functioning. TBI severity did not moderate the associations between subjective and objective cognition for memory or language domains. The pattern of results did not change when the total number of TBIs was included in the models.
Conclusions:In this DoD-ADNI sample, stronger associations between subjective and objective attention were evident among individuals with mild and moderate-to-severe TBI compared to Veterans without a TBI history. Attention/executive functioning measures (Trails A and B) may be particularly sensitive to detecting subtle cognitive difficulties related to TBI and/or comorbid psychiatric symptoms, which may contribute to these attention-specific findings. The strongest associations were among those with moderate-to-severe TBI, potentially because the extent to which their attention difficulties are affecting their daily lives are more apparent despite no significant differences in objective attention performance by TBI group. This study highlights the importance of assessing both subjective and objective cognition in older Veterans and the particular relevance of the attention domain within the context of TBI.
1 Associations of Locus of Control and Memory Self-Awareness in Older Adults with and without MCI
- Mary E Garcia, Jeanine M Parisi, Sarah Cook, Ian McDonough, Alexandra J Weigand, Alexandra L Clark, Michael Marsiske, Kelsey R Thomas
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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. 676-677
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Objective:
While loss of insight into one’s cognitive impairment (anosognosia) is a feature in Alzheimer’s disease dementia, less is known about memory self-awareness in cognitively unimpaired (CU) older adults or mild cognitive impairment (MCI) or factors that may impact self-awareness. Locus of control, specifically external locus of control, has been linked to worse cognitive/health outcomes, though little work has examined locus of control as it relates to self-awareness of memory functioning or across cognitive impairment status. Therefore, we examined associations between locus of control and memory self-awareness and whether MCI status impacted these associations.
Participants and Methods:Participants from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (mean age=73.51; 76% women; 26% Black/African American) were classified as CU (n=2177) or MCI (amnestic n=313; non-amnestic n=170) using Neuropsychological Criteria. A memory composite score measured objective memory performance and the Memory Functioning Questionnaire measured subjective memory. Memory self-awareness was defined as objective memory minus subjective memory, with positive values indicating overreporting of memory difficulties relative to actual performance (hypernosognosia) and negative values indicating underreporting (hyponosognosia). Internal (i.e., personal skills/attributes dictate life events) and external (i.e., environment/others dictate life events) locus of control scores came from the Personality in Intellectual Aging Contexts Inventory. General linear models, adjusting for age, education, sex/gender, depressive symptoms, general health, and vocabulary examined the effects of internal and external locus of control on memory self-awareness and whether MCI status moderated these associations.
Results:Amnestic and non-amnestic MCI participants reported lower internal and higher external locus of control than CU participants. There was a main effect of MCI status on memory self-awareness such that amnestic MCI participants showed the greatest degree of hyponosognosia/underreporting, followed by non-amnestic MCI, and CU participants slightly overreported their memory difficulties. While, on average, participants were fairly accurate at reporting their degree of memory difficulty, internal locus of control was negatively associated with self-awareness such that higher internal locus of control was associated with greater underreporting (ß=-.127, 95% CI [-.164, -.089], p<.001). MCI status did not moderate this association. External locus of control was positively associated with self-awareness such that higher external locus of control was associated with greater hypernosonosia/overreporting (ß=.259, 95% CI [.218, .300], p<.001). Relative to CU, amnestic, but not non-amnestic, MCI showed a stronger association between external locus of control and memory self-awareness. Specifically, higher external locus of control was associated with less underreporting of cognitive difficulties in amnestic MCI (ß=.107, 95% CI [.006, .208], p=.038).
Conclusions:In CU participants, higher external locus of control was associated with greater hypernosognosia/overreporting. In amnestic MCI, the lower external locus of control associations with greater underreporting of objective cognitive difficulties suggests that perhaps reduced insight in some people with MCI may result in not realizing the need for external supports, and therefore not asking for help from others. Alternatively, in amnestic participants with greater external locus of control, perhaps the environmental cues/feedback translate to greater accuracy in their memory self-perceptions. Longitudinal analyses are needed to determine how memory self-awareness is related to future cognitive declines.
Greater accelerometer-measured physical activity is associated with better cognition and cerebrovascular health in older adults
- Katherine J. Bangen, Amanda T. Calcetas, Kelsey R. Thomas, Christina Wierenga, Christine N. Smith, Maria Bordyug, Einat K. Brenner, David Wing, Conan Chen, Thomas T. Liu, Zvinka Z. Zlatar
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 9 / November 2023
- Published online by Cambridge University Press:
- 15 February 2023, pp. 859-869
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Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults.
Method:Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week.
Results:Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume.
Conclusions:Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.
Cognitive dispersion is elevated in amyloid-positive older adults and associated with regional hypoperfusion
- Sophia L. Holmqvist, Kelsey R. Thomas, Emily C. Edmonds, Amanda Calcetas, Lauren Edwards, Katherine J. Bangen, for the Alzheimer’s Disease Neuroimaging Initiative
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- Journal of the International Neuropsychological Society / Volume 29 / Issue 7 / August 2023
- Published online by Cambridge University Press:
- 12 September 2022, pp. 621-631
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Objective:
Cognitive dispersion across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). However, little is known regarding brain changes underlying cognitive dispersion, and the association of cognitive dispersion with in vivo AD biomarkers and regional cerebral blood flow (CBF) has received limited study. We therefore examined associations among cognitive dispersion, amyloid-beta (Aβ) positivity, and regional CBF among older adults free of dementia.
Method:One hundred and forty-eight Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent neuropsychological testing and neuroimaging. Pulsed arterial spin labeling (ASL) magnetic resonance imaging (MRI) was acquired to quantify CBF. Florbetapir positron emission tomography (PET) imaging determined Aβ positivity.
Results:Adjusting for age, gender, education, and mean cognitive performance, older adults who were Aβ+ showed higher cognitive dispersion relative to those who were Aβ-. Across the entire sample, higher cognitive dispersion was associated with reduced CBF in inferior parietal and temporal regions. Secondary analyses stratified by Aβ status demonstrated that higher cognitive dispersion was associated with reduced CBF among Aβ+ individuals but not among those who were Aβ-.
Conclusions:Cognitive dispersion may be sensitive to early Aβ accumulation and cerebrovascular changes adjusting for demographics and mean neuropsychological performance. Associations between cognitive dispersion and CBF were observed among Aβ+ individuals, suggesting that cognitive dispersion may be a marker of brain changes among individuals on the AD continuum. Future studies should examine whether cognitive dispersion predicts brain changes in diverse samples and among those with greater vascular risk burden.
When wrong answers lead us down the right path
- Kelsey R. Thomas, Rhoda Au
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- International Psychogeriatrics / Volume 34 / Issue 11 / November 2022
- Published online by Cambridge University Press:
- 01 October 2021, pp. 959-961
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Discrepancy-Based Evidence for Loss of Thinking Abilities (DELTA): Development and Validation of a Novel Approach to Identifying Cognitive Changes
- Breton M. Asken, Kelsey R. Thomas, Athene Lee, Jennifer D. Davis, Paul F. Malloy, Stephen P. Salloway, Stephen Correia
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- Journal of the International Neuropsychological Society / Volume 26 / Issue 5 / May 2020
- Published online by Cambridge University Press:
- 11 December 2019, pp. 464-479
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Objective:
To develop and validate the Discrepancy-based Evidence for Loss of Thinking Abilities (DELTA) score. The DELTA score characterizes the strength of evidence for cognitive decline on a continuous spectrum using well-established psychometric principles for improving detection of cognitive changes.
Methods:DELTA score development used neuropsychological test scores from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (two tests each from Memory, Executive Function, and Language domains). We derived regression-based normative reference scores using age, gender, years of education, and word-reading ability from robust cognitively normal ADNI participants. Discrepancies between predicted and observed scores were used for calculating the DELTA score (range 0–15). We validated DELTA scores primarily against longitudinal Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Functional Activities Questionnaire (FAQ) scores (baseline assessment through Year 3) using linear mixed models and secondarily against cross-sectional Alzheimer’s biomarkers.
Results:There were 1359 ADNI participants with calculable baseline DELTA scores (age 73.7 ± 7.1 years, 55.4% female, 100% white/Caucasian). Higher baseline DELTA scores (stronger evidence of cognitive decline) predicted higher baseline CDR-SOB (ΔR2 = .318) and faster rates of CDR-SOB increase over time (ΔR2 = .209). Longitudinal changes in DELTA scores tracked closely and in the same direction as CDR-SOB scores (fixed and random effects of mean + mean-centered DELTA, ΔR2 > .7). Results were similar for FAQ scores. High DELTA scores predicted higher PET-Aβ SUVr (ρ = 324), higher CSF-pTau/CSF-Aβ ratio (ρ = .460), and demonstrated PPV > .9 for positive Alzheimer’s disease biomarker classification.
Conclusions:Data support initial development and validation of the DELTA score through its associations with longitudinal functional changes and Alzheimer’s biomarkers. We provide several considerations for future research and include an automated scoring program for clinical use.
Psychological Symptoms and Rates of Performance Validity Improve Following Trauma-Focused Treatment in Veterans with PTSD and History of Mild-to-Moderate TBI
- Sarah M. Jurick, Laura D. Crocker, Victoria C. Merritt, Samantha N. Hoffman, Amber V. Keller, Graham M. L. Eglit, Kelsey R. Thomas, Sonya B. Norman, Dawn M. Schiehser, Carie S. Rodgers, Elizabeth W. Twamley, Amy J. Jak
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- Journal:
- Journal of the International Neuropsychological Society / Volume 26 / Issue 1 / January 2020
- Published online by Cambridge University Press:
- 29 October 2019, pp. 108-118
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Objective:
Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance.
Method:Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass).
Results:Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition.
Conclusion:Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.
Increasing Inaccuracy of Self-Reported Subjective Cognitive Complaints Over 24 Months in Empirically Derived Subtypes of Mild Cognitive Impairment
- Emily C. Edmonds, Alexandra J. Weigand, Kelsey R. Thomas, Joel Eppig, Lisa Delano-Wood, Douglas R. Galasko, David P. Salmon, Mark W. Bondi
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- Journal:
- Journal of the International Neuropsychological Society / Volume 24 / Issue 8 / September 2018
- Published online by Cambridge University Press:
- 02 October 2018, pp. 842-853
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Objectives: Although subjective cognitive complaints (SCC) are an integral component of the diagnostic criteria for mild cognitive impairment (MCI), previous findings indicate they may not accurately reflect cognitive ability. Within the Alzheimer’s Disease Neuroimaging Initiative, we investigated longitudinal change in the discrepancy between self- and informant-reported SCC across empirically derived subtypes of MCI and normal control (NC) participants. Methods: Data were obtained for 353 MCI participants and 122 “robust” NC participants. Participants were classified into three subtypes at baseline via cluster analysis: amnestic MCI, mixed MCI, and cluster-derived normal (CDN), a presumptive false-positive group who performed within normal limits on neuropsychological testing. SCC at baseline and two annual follow-up visits were assessed via the Everyday Cognition Questionnaire (ECog), and discrepancy scores between self- and informant-report were calculated. Analysis of change was conducted using analysis of covariance. Results: The amnestic and mixed MCI subtypes demonstrated increasing ECog discrepancy scores over time. This was driven by an increase in informant-reported SCC, which corresponded to participants’ objective cognitive decline, despite stable self-reported SCC. Increasing unawareness was associated with cerebrospinal fluid Alzheimer’s disease biomarker positivity and progression to Alzheimer’s disease. In contrast, CDN and NC groups over-reported cognitive difficulty and demonstrated normal cognition at all time points. Conclusions: MCI participants’ discrepancy scores indicate progressive underappreciation of their evolving cognitive deficits. Consistent over-reporting in the CDN and NC groups despite normal objective cognition suggests that self-reported SCC do not predict impending cognitive decline. Results demonstrate that self-reported SCC become increasingly misleading as objective cognitive impairment becomes more pronounced. (JINS, 2018, 24, 842–853)
Self-perceived Difficulties in Everyday Function Precede Cognitive Decline among Older Adults in the ACTIVE Study
- Sarah Tomaszewski Farias, Tania Giovannetti, Brennan R. Payne, Michael Marsiske, George W. Rebok, K. Warner Schaie, Kelsey R. Thomas, Sherry L. Willis, Joseph M. Dzierzewski, Frederick Unverzagt, Alden L. Gross
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- Journal:
- Journal of the International Neuropsychological Society / Volume 24 / Issue 1 / January 2018
- Published online by Cambridge University Press:
- 11 August 2017, pp. 104-112
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Objectives: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. Methods: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. Results: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. Conclusions: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104–112)
Longitudinal Trajectories of Informant-Reported Daily Functioning in Empirically Defined Subtypes of Mild Cognitive Impairment
- Kelsey R. Thomas, Emily C. Edmonds, Lisa Delano-Wood, Mark W. Bondi
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- Journal:
- Journal of the International Neuropsychological Society / Volume 23 / Issue 6 / July 2017
- Published online by Cambridge University Press:
- 10 May 2017, pp. 521-527
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Objectives: Within the Alzheimer’s Disease Neuroimaging Initiative (ADNI)’s mild cognitive impairment (MCI) cohort, we previously identified MCI subtypes as well as participants initially diagnosed with MCI but found to have normal neuropsychological, biomarker, and neuroimaging profiles. We investigated the functional change over time in these empirically derived MCI subgroups. Methods: ADNI MCI participants (n=654) were classified using cluster analysis as Amnestic MCI (single-domain memory impairment), Dysnomic MCI (memory+language impairments), Dysexecutive/Mixed MCI (memory+language+attention/executive impairments), or Cluster-Derived Normal (CDN). Robust normal control participants (NCs; n=284) were also examined. The Functional Activities Questionnaire (FAQ) was administered at baseline through 48-month follow-up. Multilevel modeling examined FAQ trajectories by cognitive subgroup. Results: The Dysexecutive/Mixed group demonstrated the fastest rate of decline across all groups. Amnestic and Dysnomic groups showed steeper rates of decline than CDNs. While CDNs had more functional difficulty than NCs across visits, both groups’ mean FAQ scores remained below its suggested cutoff at all visits. Conclusions: Results (a) show the importance of executive dysfunction in the context of other impaired cognitive domains when predicting functional decline in at-risk elders, and (b) support our previous work demonstrating that ADNI’s MCI criteria may have resulted in false-positive MCI diagnoses, given the CDN’s better FAQ trajectory than those of the cognitively impaired MCI groups. (JINS, 2017, 23, 521–527)
Contributors
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- By Alaine Auger, Kathleen Brager, Christopher M. Buddle, Jaret Daniels, Thomas A. Delamere, Adam Dodd, Crystal M. Ernst, Brian D. Farrell, Adrian Franklin, Donna J. Giberson, C. Michael Hall, Yupa Hanboonsong, Glen T. Hvenegaard, Kelsey Johansen, Akito Y. Kawahara, Raynald Harvey Lemelin, Jeff Lockwood, Forrest L. Mitchell, Tim R. New, David L. Pearson, Robert M. Pyle, Jessica J. Rykken, Michael J. Samways, Matt Shardlow, Edward M. Spevak, Arnold van Huis, Ko Veltman, Kristen M. Vinke, Alan L. Yen
- Edited by Raynald Harvey Lemelin, Lakehead University, Ontario
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- Book:
- The Management of Insects in Recreation and Tourism
- Published online:
- 05 December 2012
- Print publication:
- 22 November 2012, pp x-xiv
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Identification of Mild Cognitive Impairment in ACTIVE: Algorithmic Classification and Stability
- Sarah E. Cook, Michael Marsiske, Kelsey R. Thomas, Frederick W. Unverzagt, Virginia G. Wadley, Jessica B.S. Langbaum, Michael Crowe
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- Journal:
- Journal of the International Neuropsychological Society / Volume 19 / Issue 1 / January 2013
- Published online by Cambridge University Press:
- 25 October 2012, pp. 73-87
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Rates of mild cognitive impairment (MCI) have varied substantially, depending on the criteria used and the samples surveyed. The present investigation used a psychometric algorithm for identifying MCI and its stability to determine if low cognitive functioning was related to poorer longitudinal outcomes. The Advanced Cognitive Training of Independent and Vital Elders (ACTIVE) study is a multi-site longitudinal investigation of long-term effects of cognitive training with older adults. ACTIVE exclusion criteria eliminated participants at highest risk for dementia (i.e., Mini-Mental State Examination < 23). Using composite normative for sample- and training-corrected psychometric data, 8.07% of the sample had amnestic impairment, while 25.09% had a non-amnestic impairment at baseline. Poorer baseline functional scores were observed in those with impairment at the first visit, including a higher rate of attrition, depressive symptoms, and self-reported physical functioning. Participants were then classified based upon the stability of their classification. Those who were stably impaired over the 5-year interval had the worst functional outcomes (e.g., Instrumental Activities of Daily Living performance), and inconsistency in classification over time also appeared to be associated increased risk. These findings suggest that there is prognostic value in assessing and tracking cognition to assist in identifying the critical baseline features associated with poorer outcomes. (JINS, 2012, 18, 1–15)