Cognitive dispersion and its functional relevance in behavioral variant frontotemporal dementia and prodromal behavioral variant frontotemporal dementia.

OBJECTIVE: Executive dysfunction is characteristic of behavioral variant frontotemporal dementia (bvFTD) but can be challenging to detect. Dispersion-based intraindividual variability (IIV-d) is hypothesized to reflect a sensitive index of executive dysfunction and has demonstrated relevance to functional decline but has not been evaluated in bvFTD. METHOD: We report on 477 demographically matched participants (159 cognitively healthy [CH], 159 clinical Alzheimer's disease [AD], 159 clinical bvFTD/prodromal bvFTD) who completed the Uniform Data Set 3.0 Neuropsychological Battery. IIV-d was measured using the coefficient of variance (CoV; raw and demographically adjusted) across 12 Uniform Data Set 3.0 Neuropsychological Battery indicators and the informant-rated Functional Activities Questionnaire assessed daily functioning. RESULTS: Analysis of covariance showed that participants in the bvFTD/prodromal bvFTD group exhibited higher raw and demographically adjusted CoV compared to CH participants, at a very large effect size (d = 1.28-1.47). Demographically adjusted (but not raw) CoV was lower in the bvFTD/prodromal bvFTD group than the AD group, though the effect size was small (d = .38). Both CoV metrics accurately differentiated the bvFTD/prodromal bvFTD and CH groups (areas under the curve = .84), but not bvFTD/prodromal bvFTD and AD groups (areas under the curve = .59). Regression analyses in the bvFTD/prodromal bvFTD group indicated that higher IIV-d on both metrics was associated with greater daily functioning impairment, over and above covariates. CONCLUSIONS: Compared to healthy adults, individuals with bvFTD/prodromal bvFTD show greater levels of performance variability across a battery of neuropsychological measures, which interferes with everyday functioning. These data demonstrate the clinical utility and ecological validity of IIV-d in bvFTD/prodromal bvFTD, though these findings should be replicated in more diverse samples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ecological validity of cognitive fluctuations in dementia with Lewy bodies.

OBJECTIVES: Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB. METHODS: The study sample included 97 participants with consensus-defined DLB from the National Alzheimer's Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual's performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual's performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ). RESULTS: Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores). CONCLUSIONS: Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.

PROPERTIES OF A COMBINED MEASURE OF READING AND WRITING: THE ASSESSMENT OF WRITING, SELF-MONITORING, AND READING (AWSM READER).

There is significant overlap between reading and writing, but no known standardized measure assesses these jointly. The goal of the present study is to evaluate the properties of a novel measure, the Assessment of Writing, Self-Monitoring, and Reading (AWSM Reader), that simultaneously evaluates both reading comprehension and writing. In doing so, we evaluate reliability (Cronbach's alpha) and various aspects of construct-related validity, including separate criterion measures of reading and writing, and the AWSM Reader's relations with other variables, including language and executive function (EF), both of which are implicated for both reading and writing. Participants were 377 3rd, 4th, and 5th graders with or at-risk for reading and writing difficulties. Reliability was low for the AWSM Reader reading comprehension (α = .58), but good for writing (α = .75-.80). Criterion-related validity indices revealed moderate correlations with other standardized and commonly used reading and writing measures, r = .47 to .50 (all ps < .001). Additionally, validity data supported the relations of both language and EF to AWSM Reader reading and writing, with EF showing unique prediction in both reading and writing domains. Results provide initial support for the measure per se but stress the difficulty in constructing combined reading and writing measures; directions are given for future work. Results also add to data on the contributions of language and EF to both reading and writing.

Indirect Effects of Negative Mood on Opioid Misuse and Dependence via Anxiety Sensitivity Subfacets: Evidence from Adults Reporting Chronic Pain.

Background: Opioid misuse in the context of pain management exacts a significant public health burden. Past work has established linkages between negative mood (i.e., symptoms of anxiety and depression) and opioid misuse/dependence, yet the mechanisms underlying these associations have received little scientific investigation. Anxiety sensitivity (AS), the fear of the negative consequences of internal states, may be relevant to better understanding negative mood-opioid relations among adults with chronic pain. Methods: Simultaneous indirect effects of negative mood on opioid misuse and opioid dependence via lower-order factors of AS (physical, cognitive, and social concerns) were examined cross-sectionally in the present study. The study sample consisted of 428 adults (74.1% female, Mage = 38.27 years, SD = 11.06) who self-reported current moderate to severe chronic pain and opioid use for chronic pain. Results: Results indicated that negative mood was (in part) indirectly related to opioid misuse (in part) via AS physical and cognitive concerns and was (in part) indirectly related to opioid dependence via AS cognitive concerns only. No significant indirect effects via social concerns were observed. Discussion and Conclusions: Findings suggest the importance of further exploring the role of anxiety sensitivity cognitive and physical concerns in terms of opioid misuse and dependence among adults with chronic pain.

Dispersion-based cognitive intra-individual variability in dementia with Lewy bodies.

OBJECTIVE: Cognitive fluctuations are characteristic of dementia with Lewy bodies (DLB) but challenging to measure. Dispersion-based intra-individual variability (IIV-d) captures neurocognitive performance fluctuations across a test battery and may be sensitive to cognitive fluctuations but has not been studied in DLB. METHOD: We report on 5,976 participants that completed the uniform data set 3.0 neuropsychological battery (UDS3NB). IIV-d was calculated via the intra-individual standard deviation across 12 primary UDS3NB indicators. Separate models using mean USD3NB score and the Montreal cognitive assessment (MoCA) total score tested the reproducibility of the incremental value of IIV-d over-and-above global cognition. Binary logistic regressions tested whether IIV-d could classify individuals with and without clinician-rated cognitive fluctuations. Multinomial logistic regressions tested whether IIV-d could differentiate participants with DLB, participants with Alzheimer's disease (AD), and participants with healthy cognition (CH), as well as the incremental diagnostic utility of IIV-d over-and-above clinician-rated cognitive fluctuations. RESULTS: IIV-d exhibited large univariate associations with clinician-rated and non-clinician-informant reported cognitive fluctuations, which persisted when adjusting for MoCA but not the full battery mean. Of diagnostic relevance, greater IIV-d was consistently associated with DLB and AD relative to CH over-and-above global cognition and clinician-rated cognitive fluctuations. Greater IIV-d was less consistently associated with an increased probability of DLB relative to AD when controlling for global cognition. CONCLUSIONS: IIV-d accurately differentiates DLB from CH over-and-above global cognition and clinician-rated cognitive fluctuations. IIV-d may supplement a thorough clinical interview of cognitive fluctuations and serve as a standardized performance-based indicator of this transdiagnostic phenomenon. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Differential Associations Between BDNF and Memory Across Older Black and White Adults With HIV Disease.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) shows consistent associations with memory across many clinical populations, including dementia. Less is understood about the association between BDNF and memory functioning in people living with HIV (PWH). METHODS: A sample of 173 adults aged 50+ (n = 100 HIV+ and n = 73 HIV seronegative) completed a comprehensive neurobehavioral assessment and blood draw. Linear regressions predicting memory domains (learning, delayed recall, and recognition) were conducted including race (White vs. Black/African American), HIV status, BDNF, and their interactions. RESULTS: For learning and delayed recall, significant (P < 0.05) main effects for race and interactions for BDNF x race and HIV status x race were found, whereas for recognition, only a BDNF x race interaction emerged. In adjusted models, BDNF x race interactions remained for learning and delayed recall. To determine effect size, correlations were conducted between BDNF and memory domains stratified by HIV serostatus and race, and small-medium associations between BDNF and learning and delayed recall (rho = 0.29, P < 0.01; rho = 0.22, P = 0.045), but no recognition (rho = 0.12, P = 0.29) were found among Black/African American PWH. BDNF was not significantly associated with memory domains in White PWH or either HIV- sample. Follow-up analyses showed BDNF-memory specificity, such that race X BDNF interactions did not emerge for other cognitive domains. CONCLUSIONS: While limited by cross-sectional design among a small sample, particularly of White individuals, results indicate that BDNF may serve as a promising biomarker reflecting memory functioning in PWH, particularly Black/African Americans. Further work is needed to replicate findings and determine mechanisms for racial differences in BDNF associations with memory.

Predictors of rate of cognitive decline in patients with amnestic mild cognitive impairment.

OBJECTIVE: Amnestic mild cognitive impairment (MCI) is a known risk factor for conversion to Alzheimer's disease (AD). Although substantial research has been conducted on the general profile of amnestic MCI subjects and predictors of conversion to AD, research on predictors of rate of decline has been considerably less extensive. The present study sought to more systematically and comprehensively examine predictors of rate of cognitive decline in a longitudinal sample of individuals with MCI, including age, genetic vulnerability, baseline cognitive performance, and baseline neuropsychiatric severity. METHOD: Participants with single or multi-domain amnestic MCI (N = 151) were assessed at baseline and for a mean of 1.32 follow-up visits (mean interval from baseline to last follow-up = 1.61 years). RESULTS: Results showed that carriers of the ApoE ε4 allele declined more quickly on all three dementia severity measures compared to non-carriers. Older individuals did not decline more rapidly in dementia severity. Participants with lower executive functions composite scores and greater memory impairment severity at baseline predicted faster decline on dementia severity measures. Contrary to hypotheses, those with lower levels of depression at baseline declined more rapidly on dementia severity measures compared to those with higher levels of depression. CONCLUSION: Identifying potential predictors of rate of decline from amnestic MCI to AD could be clinically meaningful for prognostic purposes, understanding risk and protective factors, as well as guiding future treatments and clinical trials that could aim to target and delay progression among those patients who are vulnerable to more quickly convert to AD.

Long-term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy.

BACKGROUND: Proton radiotherapy (PRT) may be associated with less neurocognitive risk than photon RT (XRT) for pediatric brain tumor survivors. We compared neurocognitive and academic outcomes in long-term survivors treated with XRT versus PRT. METHODS: Survivors underwent neurocognitive evaluation >1 year after craniospinal (CSI) or focal PRT or XRT. Groups were compared using separate one-way analyses of covariance for the CSI and focal groups. RESULTS: PRT (n = 58) and XRT (n = 30) subgroups were similar on gender (66% male), age at RT (median = 6.5 years), age at follow-up (median = 14.6 years), and government assistance status (32%). PRT and XRT focal groups differed on follow-up interval, shunt history, and total RT dose (all p < .05), whereas PRT and XRT CSI groups differed on follow-up interval, baseline neurocognitive performance score, boost volume, and CSI dose (all p < .05). The PRT focal group outperformed the XRT focal group on inhibition/switching (p = .04). The PRT CSI group outperformed the XRT CSI group on inattention/impulsivity (both p < .05). Several clinical variables (i.e., RT dose, boost field, baseline performance) predicted neurocognitive outcomes (all p < .05). The PRT focal group performed comparably to population means on most neurocognitive measures, while both CSI groups performed below expectation on multiple measures. The XRT CSI group was most impaired. All groups fell below expectation on processing speed, fine motor, and academic fluency (most p < .01). CONCLUSIONS: Findings suggest generally favorable neurocognitive and academic long-term outcomes following focal PRT. Impairment was greatest following CSI regardless of modality. Dosimetry and baseline characteristics are important determinants of outcome alone or in combination with modality.