bluuebunny/crossref_metadata_2025_split huggingface dataset:
3 Mind-Wandering in Neuropsychiatry Diseases of Ageing
Authors: O’Callaghan Claire 
Published: December 2023

Objective:Disruptions to mind-wandering are common across neuropsychiatric disorders. Whilst the large-scale brain networks associated with mind-wandering are increasingly well understood, we know very little about what neurobiological mechanisms trigger a mind-wandering episode and sustain the mind-wandering brain state. From a clinical perspective, we aimed to understand dysfunctional mind-wandering in neuropsychiatric diseases of ageing: frontotemporal dementia, Alzheimer’s disease and Parkinson’s disease. We also tested the hypothesis that mind-wandering relates to visual hallucinations in Parkinson’s disease. From a theoretical perspective, we advance the hypothesis that the hippocampal sharp wave-ripple is a compelling candidate for a brain state that can trigger mind-wandering episodes. The occurrence of the sharp wave-ripple is heavily dependent on hippocampal neuromodulatory tone. Neuromodulatory systems that regulate the sharp wave-ripple may be crucial for understanding the disruption to mind-wandering in neuropsychiatric disease.Participants and Methods:We developed a thought-sampling task to probe mind-wandering in neuropsychiatric diseases of ageing. To explore brain patterns related to mind-wandering, we used multi-modal neuroimaging (i.e., resting state and structural scans). In separate studies, we applied these techniques in frontotemporal dementia and Alzheimer’s disease; and in Parkinson’s patients with and without visual hallucinations.Results:We showed reduced mind-wandering in frontotemporal dementia, associated with functional and structural changes across the default network. In Parkinson’s disease, we also found a reduction in mind-wandering compared with healthy controls. However, in patients with visual hallucinations, mind-wandering was preserved and associated with increased connectivity between the default network and early visual regions.Conclusions:Together, disrupted mind-wandering occurs in neuropsychiatric diseases of ageing. It may contribute to some of the more recognisable symptoms in these conditions, including apathy and hallucinations. These findings also provide a unique clinical validation of current brain network models of mind-wandering that have been developed in healthy populations. Neuromodulatory influences over mind-wandering have implications for treating impairments in this process across neuropsychiatric conditions.
2 Computerized Cognitive Practice Effects in Relation to Amyloid and Tau in Preclinical Alzheimer's Disease: Results from a Multi-Site Cohort
Authors: Young Christina B , Mormino Elizabeth C , Poston Kathleen L , Johnson Keith A , Rentz Dorene M , Sperling Reisa A , Papp Kathryn V 
Published: December 2023

AbstractObjective:There is a need to identify scalable cognitive paradigms that are sensitive enough to relate to Alzheimer's disease biomarkers (amyloid and tau) in the preclinical stage. Here, we determine whether initial performance and practice effects on the memory-focused Computerized Cognitive Composite (C3) relate to demographic variables, amyloid status [abnormal (A+), normal (A-)], and regional tau in clinically unimpaired (CU) older adults.Participants and Methods:We examined pre-randomization data from CU older adults screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. We focused on participants who completed the C3 (n=3287), most of whom completed an alternate version of the C3 again approximately 51 days later (n=4141), as well as a subset of preclinical AD participants (i.e., A+ CU) who completed the C3 and tau PET imaging with [18]F-flortaucipir (initial C3: n=354; repeat C3: n=343). C3 initial performance and practice effects were examined in relation to amyloid status (A+, A-) and continuous regional tau burden.Results:Initial C3 performance was associated with amyloid status [B(SE) = -0.075 (0.021), p < 0.001] across all participants, as well as tau burden in the medial temporal lobe (MTL) [B (SE) = -0.728 (0.220), p = 0.001], inferior temporal (IT) cortex [B (SE) = -0.782 (0.264), p = 0.003], and inferior parietal (IP) cortex [B (SE) = -0.721 (0.281), p = 0.011] amongst preclinical AD individuals. Short-term practice effects were also associated with reduced tau burden in MTL [B (SE) = -0.471 (0.202), p = 0.020], IT [B (SE) = -0.640 (0.240), p = 0.008], and IP [B( SE) = - 0.584 (0.255), p = 0.023] amongst preclinical AD participants, but were not associated with amyloid status [B (SE) = -0.018 (0.020), p = 0.348]. Critically, these effects with tau were only detected when baseline performance was accounted for presumably due to opposing influence from both practice effects and regression to the mean effects.Conclusions:This is the first study to show that performance on a brief cognitive battery administered in a multisite context is associated with both amyloid and tau among CU older adults. These findings suggest that computerized assessments may be a cost-effective and scalable approach for early detection efforts. Further, diminished practice effects on memory-based measures are associated with elevated tau burden in preclinical AD, suggesting that high-frequency cognitive testing collected over a short follow-up period may provide additional insights regarding early disease processes than single assessments.
5 Cognitive Rehabilitation Using Teleneuropsychology. A Cohort Study in South America
Authors: Canyazo Carlos Martinez , Fernandez Rodrigo S , Helou Maria B , Arruabarrena Micaela , Corvalan Nicolas , Carello Agostina , Harris Paula , Feldman Monica , Luis Calandri Ismael , Martin Maria E , Allegri Ricardo F , Crivelli Lucia 
Published: December 2023

Objective:The COVID-19 pandemic has affected the continuity of cognitive rehabilitation (CR) worldwide. However, the use of teleneuropsychology (TNP) to provide CR has contributed significantly to the continuity of treatment. The objective of this study was to measure the effects of CR via the TNP on cognition, neuropsychiatric symptoms, and memory strategies in a cohort of patients with Mild Cognitive Impairment (MCI).Participants and Methods:A sample of 60 patients (60% female; age: 72.4±6.96) with MCI according to Petersen criteria was randomly divided into two groups: 30 cases (treatment group) and 30 controls (waiting list group). Subjects were matched for age, sex, and MMSE or MoCA.The treatment group received ten weekly CR sessions of 45 minutes weekly. Pre-treatment (week 0) and post-treatment (week 10) measures were assessed for both groups. Different Linear Mixed Models were estimated to test treatment effect (CR vs. Controls) on each outcome of interest over Time (Pre/Post), controlling for Diagnosis, Age, Sex, and MMSE/MoCA performance.Results:A significant Group (Control/Treatment) x Time (pre/post) interaction revealed that the treatment group at 10 weeks had better scores in cognitive variables: memory (RAVLT learning trials p=0.030; RAVLT delayed recall p=0.029), phonological fluency(p=0.001), activities of daily living (FAQ p=0.001), satisfaction with memory performance (MMQ Satisfaction p=0.004) and use of memory strategies (MMQ Strategy p=0.00), and a significant reduction of affective symptomatology: depression (GDS p=0.00), neuropsychiatric symptoms (NPIQ p=0.045), Forgetfulness (EDO-10 p=0.00), Stress (DAS Stress p=0.00).Conclusions:This is the first study to test CR using teleNP in South America. Our results suggest that CR through teleNP is an effective intervention to improve performance on cognitive variables and reduce neuropsychiatric symptomatology compared to patients with MCI. These results have great significance in the context of the COVID-19 pandemic in South America, where teleNP is proving to be a valuable tool.
4 Association Between Plasma Neurofilament Light Chain (NfL) and Non-Verbal Abstract Reasoning in a Colombian Cohort with Autosomal Dominant Alzheimer’s Disease
Authors: Cabrera Alex Leonardo Badillo , Aduen Paula A , Martinez Jairo E. , Pineda Ana Baena , Tirado Victoria , Ospina Paula , Lopera Francisco , Quiroz Yakeel T 
Published: December 2023

Objective:Neurofilament light chain (NfL), a plasma-based biomarker for neurodegeneration, is a promising marker for early Alzheimer disease (AD) detection in individuals at increased risk. We previously reported that Presenilin1 (PSEN1) E280A carriers have increased levels of plasma NfL relative to non-carrier family members twenty years before the onset of clinical symptoms. Abstract reasoning is one of the first cognitive abilities to deteriorate in AD. Here, we examined whether levels of plasma NfL were associated with non-verbal abstract reasoning performance in non-demented PSEN1-E280A carriers and non-carriers.Participants and Methods:A total of 798 members of the Colombian kindred with the PSEN1 E280A mutation (462 cognitively-unimpaired and 336 non-carriers; mean age= 34.02 (10.53), mean education= 8.23(4.60), 57% females and 43% males) were included in the study. Participants completed the Raven’s Progressive Matrices (RPM), Mini Mental State Examination (MMSE), and underwent blood sampling. Plasma NfL concentrations were measured with a single molecule array (Simoa) method. Mann-Whitney U test and education-adjusted Spearman partial correlation were used to examine group differences and associations between abstract reasoning performance and NfL levels.Results:Non-carriers were older (p<.001) and had higher levels of education than carriers (p=.025). Compared to non-carriers, carriers had higher levels of NfL (p=.014), lower performance on the MMSE (p<.001) and on the RPM (p=.001). In the whole sample, performance on the RPM was significantly associated with age (r= -.144, p<.001), and MMSE score (r=.198, p<.001). In carriers only, performance on the RPM was negatively associated with NfL levels (r=-.121, p=.009). This association was not significant in non-carriers.Conclusions:Our findings support the hypothesis that plasma NfL levels may be indicators of disease progression and early cognitive dysfunction in autosomal dominant AD. Future work with NfL, abstract reasoning and memory with larger samples across the preclinical/prodromal spectrum will allow a more comprehensive examination of these associations.
16 Increased Financial Altruism is Associated with Alzheimer’s Disease Neurocognitive Profile in Older Adults
Authors: Weissberger Gali H. , Samek Anya , Mosqueda Laura , Nguyen Annie , Lim Aaron C. , Fenton Laura , Han Duke 
Published: December 2023

Objective:Older age is associated with an increase in altruistic behaviors such as charitable giving. However, few studies have investigated the cognitive correlates of financial altruism in older adults. This study investigated the cognitive correlates of financial altruism measured using an altruistic choice paradigm in a community-based sample of older adults.Participants and Methods:In the present study, a sample of older adults (N = 67; M age = 69.21, SD = 11.23; M education years = 15.97, SD = 2.51; 58.2% female; 71.6% Non-Hispanic White) completed a comprehensive neuropsychological assessment and an altruistic choice paradigm in which they made decisions about allocating money between themselves and an anonymous person.Results:In multiple linear regression analyses that controlled for age, education, and sex, financial altruism was negatively associated with performance on cognitive measures typically sensitive to early Alzheimer’s Disease. These included CVLT-II Short Delay Free Recall (Beta=-0.26, p=0.03); CVLT-II Long Delay Cued Recall (Beta=-0.32, p=0.04), Craft Story 21 Delayed Recall (Beta=-0.32, p=0.01), and Animal Fluency (Beta=-0.27, p=0.02). Findings held when responses were grouped according to how much was given (Gave Equally, Gave More, Gave Less) for word list memory and story memory measures.Conclusions:Findings of this study point to a negative relationship between financial altruism and cognitive functioning in older adults on measures known to be sensitive to Alzheimer’s Disease (AD). Findings also point to a potential link between financial exploitation risk and AD in older age.
21 Assessment of Semantic Memory Decline in aMCI : Naming and Semantic Knowledge of Unique and Non-Unique Entities
Authors: Roy-Cöte Frederique , Joubert Sven , Cole Jessica , Chasles Marie-Joelle , Delage Emilie , Montembeault Maxime , Rouleau Isabelle 
Published: December 2023

Objective:Semantic memory deficits have been reported in both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, the nature of this decline is still a matter of debate. The aim of this study was to explore the patterns of semantic memory impairment in aMCI by examining performance on naming tasks, and on tests assessing both general and specific semantic knowledge.Participants and Methods:Participants were divided in two groups matched for age and education, one comprising 33 aMCI individuals and the other 39 healthy controls. Three experimental tests assessing naming and semantic knowledge of unique items of famous persons (FACE) and places (PLACE), logos recognition (LOGO: brands and pictograms), and non-unique entities (Boston Naming Test: BNT) were administered, and the performance of the two groups was compared.Results:Lower scores were observed on all naming tests (PLACE, FACE, LOGO and BNT) in the aMCI group compared to controls. On the PLACE test, the general knowledge mean score (M=84.5, SD=12.9) was significantly higher than the specific knowledge mean score (M=54.2, SD=18.5) in aMCI participants (t(31)=11.9, p<.001), but not in controls (general: M=92.2, SD=11.1; specific: M=73.7, SD=15.8), and there was a significant Group X Type of knowledge interaction (F(1,1)=15.13, p <.001, n2 = 18). On the FACE test, in addition to significant group and condition (naming, semantic questions) main effects, a significant interaction was found (F(1,1)=7.19, p = .009, n2 = .09). On the LOGO task, controls were significantly better on brand items (M= 94.4, SD=10.5) than on pictograms (M=83.3, SD=12.2), while no significant difference was noted in aMCI (brands: M=81.5, SD=22.6; pictograms: M=77.5, SD=14.1). Lastly, on the BNT, aMCI participants benefited more from phonemic cues than controls (F(1,1)=16.56, p<.001, n2=19), suggesting a lexical access deficit, in addition to their semantic memory impairment.Conclusions:This study adds to the growing evidence confirming the presence of semantic memory deficits in aMCI. Specific semantic knowledge seems to be more affected than general semantic knowledge, a finding reported in previous studies. Lexical access deficits, in addition to semantic decline, were also observed in the aMCI group. These results allow for a better understanding of the pattern of semantic memory deficits in the prodromal stage of AD and could potentially facilitate diagnosis of aMCI.
28 Traumatic Brain Injury and Genetic Risk for Alzheimer's Disease Influence ß-Amyloid Levels
Authors: Moody Jena N , Howard Erica , Prieto Sarah , Valerio Kate E , Hayes Jasmeet P 
Published: December 2023

Objective:Traumatic brain injuries (TBIs) are a common occurrence among Veterans and may increase risk for neurodegenerative diseases, such as Alzheimer's disease (AD). Neuropathological correlates of AD, including buildup of ß-amyloid (Aß) plaques, formation of neurofibrillary tangles, and cortical atrophy, begin years before the onset of noticeable clinical and cognitive symptoms, emphasizing the importance of identifying early risk factors that could be targeted to prevent the development of AD. Of note, Aß ratios (e.g., Aß 42/40) have been shown to efficiently capture brain amyloid accumulation in prodromal AD, and thus may serve as a useful biological marker of preclinical AD. The present study investigates the mechanism by which TBI is associated with AD by examining the synergistic effects of TBI and genetic risk for AD on Aß among aging Veterans without dementia.Participants and Methods:Participants included 88 White, Non-Hispanic/Latino male Vietnam War Veterans (Mage = 68.3 years) from the Alzheimer's Disease Neuroimaging Initiative Department of Defense (ADNI DoD) cohort, 49 of whom reported a history of at least one mild, moderate, or severe TBI. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Aß levels were extracted from cerebrospinal fluid and Aß 42/40 ratios were calculated as an index of Aß deposition in the brain. Linear regression models were run to determine if TBI history and polygenic risk influence Aß 42/40 levels. An ANCOVA was implemented to examine the interaction between TBI severity and polygenic risk. Covariates in all models included age, education, and posttraumatic stress disorder symptoms.Results:Results demonstrated a significant interaction between TBI and genetic risk on Aß 42/40 (B = -0.45, Puncorrected = 0.029, Pcorrected = 0.0495). Specifically, higher polygenic risk was associated with lower Aß 42/40 ratio, suggesting greater Aß burden in the brain, among those with a history of TBI (pr = -0.33, P = 0.024) compared to individuals without a history of TBI (pr = 0.17, P = 0.308). This relationship trended towards being stronger as a function of increasing TBI severity (F(2, 77) = 3.01, P = 0.055).Conclusions:These results show that, in the context of TBI, higher genetic risk for AD is associated with greater AD-related pathology, particularly with more severe injuries. TBI and polygenic risk may implicate similar biological pathways, notably amyloid precursor protein processing, to increase Aß burden in the brain and likelihood of progression to AD in future years. These findings could inform early intervention techniques to delay or preclude conversion to AD.
32 Altered Resting State EEG Spectral Properties in Older Individuals at High Risk for Alzheimer’s Disease
Authors: Zakrzewski Jessica J. , Gemelli Zachary , Korthauer Laura 
Published: December 2023

Objective:Onset of Alzheimer’s disease (AD) pathology is estimated to begin 20-30 years prior to clinical symptom onset. Resting state EEG may yield useful early biomarkers of pathology, but its use along the AD clinical continuum is still limited, especially in individuals who are at high risk for AD but have yet to show symptoms. EEG waveform oscillations are classified based by frequency range (alpha, beta, theta, delta). Changes within these frequency bands have been identified in individuals with AD-dementia as compared to those with MCI and normal aging. Typical changes involve increases in low frequency power bands of delta and theta and decreases in beta and alpha frequencies, particularly in more posterior brain regions. However, these methods have yet to be explored in cognitively normal individuals who are at high risk for AD, as work has shown between individuals with MCI and healthy older adults.Participants and Methods:We compared differences in resting state EEG between older adults (age 60+) at high risk for AD (positive family history, genetic risk defined as carrying 1 + ApoE ε4 alleles) and individuals at low risk (negative family history, no ε4 allele). We collected 1) neuropsychological test performance; 2) self-report measures of subjective cognitive complaints and cognitive reserve; and 3) five minutes of eyes-open resting state EEG using 64-channel active electrodes. Clusters of three electrodes were average for regions and absolute power within 5 frequency bands was calculated. Theta/beta ratio was calculated by dividing absolute power of bands at its respective site. Correlations between absolute power for specific regions, self-report measures, and neuropsychological test scores.Results:Analysis of 20 individuals collected to date (14 high risk, 6 low risk) found associations (p<0.05) between risk group and beta and gamma power across multiple electrode clusters, with high-risk individuals having higher power. Significant correlations were also found between calculated measures of cognitive reserve and posterior theta/beta ratio, subjective cognitive complaints and beta power, and neuropsychological test composites of learning performance with delta and executive functioning with frontal theta power.Conclusions:This work provides preliminary evidence for differences in resting state EEG activity in those at risk for AD, prior to onset of clinical symptoms. Future work will examine patients with mild cognitive impairment as a comparison group to characterize resting state EEG across the early AD continuum.
47 Amyloid/Tau Ratio and Early Predictors of Alzheimer's Disease
Authors: Rising Shant , Kim Sung , Nolty Anne , Arakaki Xianghong 
Published: December 2023

Objective:Early cognitive signs of Alzheimer's disease are often subtle and go unnoticed until they become more prominent and debilitating. Thus, symptoms begin long before an actual Alzheimer's diagnosis is given. However, it is known that cognitively healthy older individuals with lower amyloid/tau ratios (PAT) are more likely to develop Alzheimer's disease than those with higher amyloid/tau ratios (NAT). Therefore, we explored whether this ratio can be used in conjunction with neuropsychological tests to isolate cognitive predictors of Alzheimer's disease amongst cognitively healthy older adults. We were interested in potential group differences on the California Verbal Learning Test, Second Edition (CVLT-II) Long Delay Free Recall scores and Cued Recall scores. We hypothesized that: (a) individuals in the PAT group would have weaker CVLT-II Long Delay Free Recall scores than individuals in the NAT group; and (b) individuals in the PAT group would recall fewer words on the CVLT-II Long Delay Cued Recall trial than individuals in the NAT group.Participants and Methods:There were 115 older individuals recruited via Huntington Medical Research Institutes and the University of Southern California who had their cerebral spinal fluid extracted to measure amyloid/tau ratios. They completed the California Verbal Learning Test-II as part of a larger neuropsychological battery and were determined to be cognitively healthy. The mean age of these participants was 74.5 years (SD = 8.3), and there were 36 who met the threshold for the amyloid/tau ratio associated with Alzheimer's disease (PAT) while the other 79 did not (NAT). A hierarchical linear regression tested the hypotheses, with two blocks used for the analyses. Block 1 for both analyses contained variables to control for the potential effects of various factors in performance on the Long Delay tasks. Block 2 consisted of the amyloid groups (NAT vs. PAT).Results:After controlling for age, sex, education, body mass index, Montreal Cognitive Assessment scores, and depression, we found no significant difference between CVLT-II Long Delay Free Recall scores or Long Delay Cued Recall scores for the two groups.Conclusions:While no significant difference was found on the long delay trials of the CVLT-II, it is important to note that it is unclear at what stage Alzheimer's related decline begins or can be detected using cognitive testing. Longitudinal studies would help to better understand if this lack of association holds true over time. Other aspects of the CVLT-II, such as intrusions and repetitions, would also help to better understand the different ways that symptoms of Alzheimer's disease can manifest early on.