bluuebunny/crossref_metadata_2025 huggingface dataset:
81 Developing and Validating for Cognitive Screening Tools for Identifying and Intervening Dementia among Older Persons in Rural Uganda.
Authors: Batange Haruna , Ddumba Isaac , olal Christine Jane
Published: December 2023

Objective:

The study aimed to develop, validate and field test the cognitive screening tool for use in outpatient departments within health facilities in Uganda.

Participants and Methods:

In the rural eastern region of Uganda, twenty-three (23) purposively selected health facilities and administered a scientifically derived cognitive screening tools to all eligible older persons. We conducted an inter-rater reliability in all the health facilities using three raters. Diagnosis of dementia (DSM IV) was classified as a major cognitive impairment and was quality checked by physiatrist who were blinded to results of the screening assessment.

Results:

The area under the receiver operating characterizes (AUROC) curve in health facilities was 0.912. The inter-rater reliability was good (Intra-class correlation coefficient of 0.692 to 0.734). the predictive accuracy of the tool to discriminate between dementia and other cognitive impairment was 0.892. In regression modal, the cognitive screening tool, didn’t appear to be biased by age.

Conclusions:

The cognitive screening tool if performed well among the older persons, can be proved useful for screening dementia in other developing countries.
86 Subjective Executive Dysfunction Mediates Relationship Between Perceived Sleep Quality and Societal Participation in Veterans with TBI
Authors: Ramirez Nathan R. , Walker Nicole C. , Madore Michelle R.
Published: December 2023

Objective:

Perceived poor sleep quality is the most commonly reported issue among veterans with a history of mild traumatic brain injury (mTBI). Poor sleep can impact aspects of objective and subjective executive functioning abilities (e.g., planning, organization, decision-making) and lead to decreased societal participation. However, less is known about how perceived executive dysfunction impacts the relationship between perceived poor sleep and societal participation in veterans with a prior history of mTBI. We hypothesized that executive dysfunction mediates the relationship between subjective sleep quality and societal participation.

Participants and Methods:

Participants included sixty-two U.S. veterans [Age: M=41.73 (SD=13.19); Education: M=15.16 (SD=2.20); 14.5% female]. The participants completed the Mayo-Portland Adaptability Inventory - 4 (MPAI-4; total scores), the Behavior Rating Inventory of Executive Function - Adult (BRIEF-A; subscale planning/organizing), and the Pittsburg Sleep Quality Index (PSQI; total scores). 21 participants met diagnostic criteria for Post-traumatic stress disorder (PTSD) [as determined by a cutoff score of 45 on the PTSD Checklist for DSM-5 (PCL-5)]. A mediation analysis was utilized to examine the impact of executive functions on the relationship between perceived sleep quality and societal participation. Mediation analyses were conducted via linear regression modeling using SPSS Version 27. Post hoc analyses were conducted to control for PTSD, which is common in veteran populations.

Results:

The total PSQI scores significantly predicted MPAI-4 total scores F(1, 53) = 16.740, p < .001 (R2= .55) when controlling for PTSD diagnoses. A mediation analysis showed that BRIEF-A Planning/Organizing T-scores partially mediate the relationship between PSQI scores and MPAI-4 scores when controlling for PTSD diagnoses F(2, 54) = 12.055, p < .001 (R2 = .61).

Conclusions:

Results suggest that per000eived sleep quality impacts societal participation. However, how patients perceive their executive functioning abilities partially mediates the relationship between perceived sleep quality and societal participation, such that perceived poor sleep quality leads to reduced societal participation when there is subjective executive dysfunction. Therefore, clinical interventions should focus on the cognitive rehabilitation of executive functioning among veterans with a history of mTBI to improve their subjective experience. Ultimately, these efforts may improve veterans’ participation and utilization of healthcare services.
92 To know or not to know: A case of CADASIL highlighting the ethical dilemmas of genetic testing among families carrying a highly heritable neurological condition
Authors: Coady Alanna , Piercy Jamie , Miller Harry
Published: December 2023

Objective:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of cerebral small vessel disease leading to early cerebrovascular changes. These changes result from mutations in the NOTCH3 gene that cause progressive accumulations of granular osmiophilic material (GOM) deposits, thickening arterial walls and reducing or restricting blood flow in the brain. The clinical presentation of CADASIL is characterized by migraines with aura, early and recurrent strokes, progressive cognitive impairment, and psychiatric disturbances. CADASIL is rare but frequently underrecognized or misdiagnosed. A genetic condition with a 50% risk of inheritance from an affected parent, the gold standard for diagnosis is genetic testing to determine the presence of mutations in the NOTCH3 gene. This presentation aims to familiarize neuropsychologists with the condition of CADASIL through a unique case study highlighting important psychological, social, and ethical considerations raised by genetic testing.

Participants and Methods:

This case study presents a 67-year-old, right-handed, married female diagnosed with CADASIL who was referred for neuropsychological evaluation of cognitive function and low mood concerns following multiple ischemic events.

Results:

Results revealed severe cognitive deficits in domains of attention, learning, and memory. Her superior verbal abilities and executive function remained largely intact. Assessment of mood revealed elevations in symptoms of depression and anxiety. The patient was aware of CADASIL in her father, paternal aunt, and younger brother, but elected to forego any genetic testing to confirm whether she had the condition until she experienced a stroke at age 61. She has two adult children who have also elected to forego testing and currently remain asymptomatic. Cognitive profile, mood disturbances, and patient perspectives on refraining from pre-symptomatic genetic testing for CADASIL diagnosis will be discussed.

Conclusions:

Aspects of this case are consistent with a small body of literature evidencing distinct psychological, emotional, and social challenges among families carrying genetic risk of CADASIL. While providing an example of an often underrecognized neurological disorder with which neuropsychologists should be familiar, this case uniquely raises ethical questions relevant to care providers and current treatment guidelines regarding genetic testing among families carrying highly heritable neurological conditions. In particular, personal ethical challenges around deciding to pursue or forego pre-symptomatic testing, and implications for family planning, highlight the importance of genetic counseling for affected families.
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

Objective:

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.
54 Neuropsychiatric Symptoms in Mild Cognitive Impairment and Dementia with Lewy Bodies
Authors: Nayares Claudia , Dadawalla Ali F , Cain Rene , Alving Loren , Lent David D , Wright Matthew J , Woo Ellen
Published: December 2023

Objective:

Neuropsychiatric symptoms (NPS) can be observed in mild cognitive impairment (MCI) and dementia. Hallucinations are a core clinical symptom of Dementia with Lewy Bodies (DLB). In this study, we investigated NPS in healthy control and MCI groups who would later be diagnosed with DLB to determine which symptoms would present early.

Participants and Methods:

Participants included those originally diagnosed as healthy controls (n=55), MCI with DLB etiology (n=215), and DLB (n=1059). The control and MCI groups progressed to DLB at later visits in the study. NPS data were collected using the Neuropsychiatric Inventory Questionnaire (NPI-Q) that was obtained from the National Alzheimer's Coordinating Center.

Results:

To determine which NPS presented early in the DLB course, we ran ANCOVAs to assess the role of original diagnosis on each NPS, using age as a covariate and applying Bonferroni correction. The control and MCI groups, who were later diagnosed with DLB, had greater severity of delusions, hallucinations, agitation, and apathy than the DLB group. The MCI group that would later be diagnosed with DLB had greater severity of anxiety and motor symptoms than the DLB group. The control group had greater irritability severity than the DLB group, and the controls had greater nighttime behavior severity than the MCI group, who had greater severity than the DLB group.

Conclusions:

Overall, we found that NPS present early in those who will be diagnosed with DLB, even when they are diagnosed as healthy controls. These results suggest that examination of NPS is important even in healthy adults, and their presence may be the onset of the DLB process before an official diagnosis of the condition.
56 Stereological Densities of Neuronal Tau Inclusions in Corticobasal Degeneration are Anatomically Distinct in PPA vs bvFTD
Authors: Minogue Grace , Kawles Allegra , Zouridakis Antonia , Keszycki Rachel , Coventry Christina , Gill Nathan , Zhang Hui , Rogalski Emily , Weintraub Sandra , Mao Qinwen , Flanagan Margaret , Castellani Rudolph , Mesulam M-Marsel , Geula Changiz , Gefen Tamar
Published: December 2023

Objective:

Primary progressive aphasia (PPA) is a dementia syndrome characterized early in its course by gradual dissolution of language and is associated with asymmetric atrophy in the language-dominant hemisphere (usually left). In contrast, behavioral variant frontotemporal dementia (bvFTD) is a dementia syndrome characterized by a progressive early decline in personality and comportment and is associated with relatively symmetric or rightward predominant bifrontal atrophy. This study analyzed the regional and hemispheric distributions of neuronal tau inclusions of the corticobasal degeneration variant of FTLD-tau pathology (FTLD-CBD) in individuals with PPA or bvFTD. The goal was to establish clinicopathologic concordance between FTLD-CBD and behavioral/comportmental vs aphasic dementia syndromes.

Participants and Methods:

Seven participants were clinically diagnosed with PPA and 6 were diagnosed with bvFTD. All had FTLD-CBD as the principal neuropathologic diagnosis at postmortem study. Sections from the following cortical regions were stained immunohistochemically with AT-8 to visualize neuronal tau inclusions: bilateral middle frontal gyrus (MFG), inferior parietal lobule (IPL), superior temporal gyrus (STG); and unilateral occipital cortex (OCC). Bilateral anterior temporal lobes (ATL) were analyzed in PPA cases only. Unbiased stereological analysis was performed to compare regional and hemispheric distributions between and within PPA vs. bvFTD groups.

Results:

Overall neocortical (MFG+STG+IPL) tau densities were significantly greater in the PPA group compared to the bvFTD group (p<0.05). Within the bvFTD group, the highest densities of tau inclusions were observed in the right MFG (mean=6,871.17; SD=3,220). In the PPA group, highest densities were observed in the left ATL (mean=9,901.81; SD=6,871). There was leftward hemispheric asymmetry of tau inclusions in IPL, STG and ATL which trended towards significance in the latter (p=0.083). Cortical distributions were symmetric or rightward predominant within the bvFTD group. Occipital cortex was devoid of inclusions.

Conclusions:

Preliminary stereological findings of FTLD-CBD tau inclusions suggest that the distributions of pathologic tau are different across two distinct clinical dementia phenotypes. The presence of left-sided neuronal tau inclusions in PPA is concordant with the aphasic phenotype whereas symmetric and frontal-predominant densities in bvFTD are consistent with comportmental dysfunction.
61 The Impact of Cognitive Reserve on Executive Function in Dementia
Authors: Tabaza Raghad , Bennett Lauren , Loza Sandra , Liu Stephanie , Lee Lisa
Published: December 2023

Objective:

Cognitive reserve (CR) refers to how flexibly and efficiently the individual makes use of available brain resources. Early-life education, midlife social and occupational activities, and later-life cognitive and social interactions are associated with greater CR. Years of education, premorbid intellectual (IQ) functioning, linguistic ability, and occupational complexity are often used as proxies of CR. CR theory seeks to explain discrepancies between the extent of disease pathology and clinical presentation amongst individuals with dementia. In the presence of Alzheimer’s Disease (AD) pathology, higher CR is associated with slower declines in executive functioning (EF). The current study examined the correlation between CR and EF performance across various stages of dementia severity as measured by the total score on the Clinical Dementia Rating Scale (CDRS).

Participants and Methods:

The study cohort consisted of 269 individuals who had completed measures of EF and the CDRS from phase 1 of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Individuals who scored less than 2 on the CDRS were included in the MCI group (n=197), while individuals that scored 2 or higher on the CDRS were included in the dementia group (n=73). A simple linear regression was utilized to compare the MCI group to dementia group across CR and EF performance.

Results:

There was significant correlation between CR and EF performance in the MCI group as quantified on total CDRS score (F (200) = .353, p = .0, p < .05). CR was not observed to be predictive of EF in the dementia group (F (200) = .031, p = .666, p > .05).

Conclusions:

Findings are consistent with prior research suggesting CR is protective during early stages of dementia, but not in the later disease stages. As prior research has shown the expression of dementia is based on a complex interaction between genetic and lifestyle factors that are unique to each person, future research exploring the potentially protective role of CR amongst pre-symptomatic adults with a genetic predisposition for developing dementia may expand our understanding of the potential role of CR on dementia prevention and progression.
67 Prospective Memory Accuracy and Speed in Mild Cognitive Impairment and Alzheimer's Disease
Authors: Sivaramakrishnan Krithika , Saravia Sarah , Chapp Andrew , Sidhu Jasman , Xiong Kaelyn , Tran Austin , Lent David , Alving Loren , Wright Matthew , Woo Ellen
Published: December 2023

Objective:

Prospective memory (PM) is the ability to execute a planned action in the future (e.g., remembering to take medication before going to bed). Prior work has suggested that PM failure can account for 50-80% of reported memory problems. Research has also shown that PM becomes increasingly impaired in the Alzheimer's disease (AD) process. To our knowledge, most PM studies use PM accuracy as a measure of PM performance. However, examining the speed of the response as it relates to the AD process remains relatively unexplored. In this study, we examined both PM accuracy and speed in healthy aging, mild cognitive impairment (MCI), and AD.

Participants and Methods:

Participants included healthy older controls (N=65), persons with MCI (N=70), and persons with AD (N=11). The PM task was embedded within a working memory task as PM demands often occur during an ongoing activity in everyday life. For the working memory component of the PM task, participants were shown a series of words and asked to continuously monitor the words while maintaining the last 3 in memory. All words were displayed within 1 of 6 background patterns. For the PM component, participants were asked to press "1" on the keyboard whenever they were shown a particular background pattern on the screen. PM abilities were measured using the median response time and total accuracy.

Results:

Age was correlated with PM accuracy. An ANCOVA, controlling for age, and examining the impact of diagnosis on PM accuracy, was significant. Post-hoc tests revealed a trend toward the AD and MCI groups being less accurate than healthy controls. In contrast to accuracy, age was not related to PM speed. An ANOVA examining the impact of diagnosis on PM accuracy found that the AD group responded faster than healthy controls. The MCI group did not show differences in speed from the healthy control and AD groups.

Conclusions:

Overall, the pattern of results differed in accuracy and speed of PM performance. There was a trend for the MCI and AD groups being less accurate than the controls, with no difference in performance between the MCI and AD groups. However, the AD group responded more quickly than the controls, which may have impacted their accuracy. These findings indicate that PM performance differences among groups can be detected by examining speed and not just accuracy. As speed appears to be an essential aspect involved in PM performance, future research should consider incorporating speed as a measure of PM performance when examining PM differences in populations.
72 Boston Naming Test Performance Improves with Increasing Age: What's Wrong with this Picture?
Authors: Hamberger Marla J
Published: December 2023

Objective:

As word finding or "naming" impairment is a symptom of multiple neurological conditions, naming assessment is an integral component of most neuropsychological evaluations. For decades, the Boston Naming Test (BNT) has been, and remains, the most widely used measure of naming. Although it has been shown that naming is generally stable from young adulthood through middle age, we have observed, clinically, that young adults tend to have greater difficulty on the BNT than older adults. Considering that the BNT was developed more than 50 years ago, and that language and culture change over time, we hypothesized that 1) increasing age would be associated with stronger performance on the BNT, whereas 2) there would be no association between age and naming performance on more recently developed naming measures.

Participants and Methods:

Participants were healthy adults who served as normative subjects in the revision study of the Auditory (ANT) and Visual Naming (VNT) Tests. Due to known effects of education level on BNT performance, we excluded those with less than 16 years of education, targeting young adults through middle age, resulting in 118 adults, 20 through 50 years of age (mean age: 32.9 ± 9.2 years; mean education: 16.8 ± 1.2 years; mean FSIQ: 106.0 ± 12. 6). All participants were native English speakers or learned English by age 5 and were fully educated in English. Untimed accuracy (i.e., response within 20 seconds) is the standard performance measure for the BNT; the ANT and VNT additionally include tip-of-the-tongue (TOT) scores, which incorporate response time and reliance on phonemic cueing (TOT score = number of items named in > 2 seconds but < 20 seconds, plus items named correctly after 20 seconds, following a phonemic cue). Pearson correlations examined the relation between age and naming performance on the BNT, ANT and VNT.

Results:

Pearson correlations revealed a small but significant, positive correlation between age and BNT performance (r =.22, p = .017), yet no correlation between age and performance on the ANT (ANT Accuracy: r = .05, p=.60, ANT-TOT: r = -.14, p = .12) or VNT (VNT Accuracy: r = .04, p=.67, VNT-TOT; r = -.03, p = .72).

Conclusions:

In this sample of healthy adults, naming performance improved with increasing age on the BNT; however, while vocabulary knowledge may broaden, naming efficiency should not improve with age. By contrast, we found no relation between age and naming performance on the more recently developed ANT and VNT. Results underscore the need to revise test stimuli on verbal measures, particularly those that assess naming, and suggest caution in interpreting BNT performance in young adults, as poor BNT performance might not accurately represent their true naming ability.
76 Follow-up of the Therapeutic Effects of Integrative Neuropsychological Training Model for Executive Functions Deficits in School-age Children Born Very Low Birth Weight with Normal Early Development-A Preliminary Report
Authors: Shen Ching Hua , Huang Chao Ching , Lin Chii Jeng , Guo Nai Wen
Published: December 2023

Objective:

The preschool children born very low birth weight(VLBW) still have executive functions(EFs) deficits even with normal early development(Ni, Huang, & Guo, 2011). Consequently, early intervention might be more important than expected. This study aims to investigate the follow-up outcome of the therapeutic effects of integrative neuropsychological training model(INTM) focused on EFs for school-age VLBW children with EFs deficits.

Participants and Methods:

The VLBW children, recruited from the Regional Cohort Network for premature infants who were admitted to neonatal intensive care units, had normal scores in Bayley and Wechsler Intelligence systems before 6 years old. They also received follow-up neuropsychological assessment for EFs at 6 or 8-year-old. The deficits of EFs were defined from the result of Digit Span Subtest of WISC-IV, Knox's Cube Test(KCT), Tower of London(ToL), Wisconsin Card Sorting Test(WCST), and Comprehensive Nonverbal Attention Test Battery(CNAT). A total of 8 VLBW children with EFs deficits were recruited and received EFs training at 6 or 8-year-old. The INTM combined with Comprehensive Memory Training System(CMTS), Executive FUNction Training(EFT), and multi-ecological materials focused on enhancing the four aspects of EFs, including working memory, planning, cognitive flexibility, and inhibition ability. Then, they received follow-up neuropsychological assessment for EFs at 8 or 10-year-old.

Results:

The results showed that all children got benefits from 20 hours of INTM and most of the EF aspects remained improved at follow-up. A total of 8 VLBW children with an average of 3.4 aspects EFs deficits had an average of 1.4 aspects of EFs deficits left at the follow-up. More precisely, 5 of them had 1 aspects of EFs deficits and 3 of them had 2 aspects of EFs deficits.

Conclusions:

This study revealed that such a short-term INTM had long-term effects in enhancing the EFs of those VLBW children who had normal early development but later grew into EFs deficits at school-age. Besides, their EFs are still improving even after two years of intervention. Further study on more subjects with longer follow-up might help VLBW children to achieve better neuropsychological function.