Free Recall Scores Research Articles

B - 86 Neurobehavioral Examination Total Memory Score as a Screener for Cognitive Impairment Diagnosis

Abstract Objective The neurobehavioral exam (NBE) quickly assesses patient’s neurological and behavioral status. This study aims to determine whether an individual’s NBE memory subtest is an effective screening tool for predicting cognitive diagnosis following a comprehensive neuropsychological evaluation. Method Data was collected from a clinical population of 173 adults (< 60 years old). Each patient was administered the NBE before comprehensive neuropsychological testing. The Total Memory Free Recall (TMFR) score was compared to the final cognitive diagnosis. Descriptive statistics, linear regression, and receiver operating characteristic (ROC) curve analysis were conducted with IBM SPSS. Results Linear regression indicates that the TMFR accounts for 26.1% of the variance in the cognitive diagnosis (F (1, 171) = 60.29, p = <0.001, adjusted R2 = 0.26). Area under the curve (AUC) indicated good discriminative ability for screening patients with and without cognitive impairment based on their total memory recall score (AUC = 0.83). A TMFR raw score of <6 was determined as the optimal cutoff point for screening cognitive impairment yielding a sensitivity of 0.96 and a specificity of 0.62. Conclusion(s) The analyses completed indicate that TMFR on the NBE is predictive of cognitive diagnosis following comprehensive neuropsychological testing. Total memory recall raw score can be used as a screening measure for identifying cognitive impairment and making appropriate referral for comprehensive neuropsychological assessment.

QOL-23. POTENTIAL MYELIN REPAIR AFTER IRRADIATED PEDIATRIC BRAIN TUMOR: A MAGNETIZATION TRANSFER IMAGING ANALYSIS

Abstract BACKGROUND Exercise training and metformin treatment may improve cognition after cranial irradiation in pediatric brain tumors (PBT), but the neuronal mechanisms underlying the effect of these interventions remains unknown. Magnetization transfer imaging (MTI) is an imaging technique that may be sensitive to white matter microstructure – including myelin. METHODS In this work, we analyzed changes in magnetization transfer ratio (MTR) over a 12-week period in irradiated PBT survivors who participated in pilot clinical trials entailing 12 weeks of exercise training (exercise group, n=17), or metformin treatment (n=12). Pre- and post-intervention assessment included MRI scanning and neurocognitive tests. A no intervention control group, (n=7) was also included and seen before and after a 12 week period of time. We used a longitudinal Tract-Based Spatial Statistics (TBSS) approach to analyze differences in MTR across the 12 weeks in the three groups, using as covariates: age at baseline, sex, handedness, age at diagnosis and delay from diagnosis. Then we performed correlations between mean MTR changes and behavioral outcomes. RESULTS Clusters of significant increase in MTR were observed in the right temporal lobe in the exercise group after intervention and in the right minor forceps in the metformin group after treatment. These changes respectively correlated with higher performance in free recall score in exercise group and with higher performances in inhibitory control and attention in metformin group. There was no difference in MTR changes between groups nor within the control group. DISCUSSION This exploratory work suggests either a 12-week period of exercise training or metformin may promote myelination in PBT survivors in brain regions. These changes appear to be associated with improved memory and executive function, two core domains of neurocognitive deficit in this population.

Exploring auditory temporal resolution and dichotic listening skills among individuals with type 2 diabetes mellitus

The study aimed to explore the auditory temporal resolution and dichotic listening skills in patients with type 2 diabetes mellitus (T2DM) and identify associated health-related factors. Using a cross-sectional design, 87 adults with T2DM and 48 non-diabetic controls, all with normal hearing, participated. The two central auditory processing (CAP) skills were assessed through the Gaps-In-Noise (GIN) and Dichotic-Digits Listening (DDL) tests. T2DM participants underwent blood tests to measure various health-related factors. In the GIN test, the shortest gap threshold (GapTh) obtained across both ears was significantly higher in the diabetic group (9.1 ± 2.4 ms) compared to the non-diabetic group (7.5 ± 1.5 ms), and the score of correctly identified gaps (GapSc) in the diabetic group (45±11 %) was significantly lower than GapSc in the non-diabetic group (52±9 %), p < 0.001. In the DDL test, the free-recall score (73.8 ± 18.5 %) across both ears and the right-ear advantage (-1.3 ± 20.6 %) in the diabetic group were significantly lower than the free-recall score (85.8 ± 11.9 %) and right-ear advantage (6.9 ± 11.9 %) in the non-diabetic group, p < 0.005. Furthermore, the duration of diabetes, eGFR level, retinopathy, carotid plaque, fasting blood glucose level, and HDL-C (good cholesterol) level were factors significantly associated with performances in the GIN and/or DDL tests for T2DM participants. In conclusion, individuals with T2DM are at risk of reduced auditory processing skills in temporal resolution and dichotic listening, impacting their speech understanding. Six health-related factors were identified as significantly associated with CAP skills in T2DM patients.

Habitual consumption of anthocyanin is associated with improvements in mood and cognitive performance in older people with memory complaints

The role of flavonoids on cognitive performance in older adults has been intensively studied, with the subclass of anthocyanins showing promising outcomes(1). However, there is conflicting evidence in the case of individuals at high risk of developing dementia, namely those with mild cognitive impairment (MCI). A recent study has suggested that cognitive scores in people with MCI were higher in those who had higher anthocyanin intake (&gt;10 mg)(2). Baseline data from 65 participants of an ongoing clinical trial that had an MIS (Memory Index Score) score ≤ 13 with self-reported subjective memory complaints, (mean age 69.1y ± 6.2) were used to investigate the relationship between dietary anthocyanin intake and indices of mood and cognitive performance. Repeated 24-hour dietary intake was recorded through Intake24 (a computer-based program) for three days (2Xweekday and 1Xweekend day) and anthocyanin intake was quantified using the PhenolExplorer food composition database. The primary outcome of interest was the Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall (FCSRT+IR) (assesses auditory anterograde memory functioning), while other cognitive functions assessed included: Spot the Word-2 (assessing premorbid estimate); Oral Symbol Digit Test (speed of processing); List Sorting (working memory); Trail Making Test A &amp; B (speed of processing/executive function); and Verbal Fluency (language/semantic memory). Subjective memory complaints were assessed using the Memory Assessment Clinic-Q (MAC-Q) and mood was assessed using the Geriatric Depression Scale (GDS). Independent t-tests were used to compare differences in cognitive tasks and mood scores between high (&gt;10 mg/d) and low consumers of anthocyanins (&lt;10 mg/d). There was a trend for high anthocyanin consumers (n = 35, median = 44.87 (10.01, 177.83)) to score better on FCSRT-Delayed Free Recall scores (16.57 ± 3.74) compared to lower consumers (n = 30, median = 0.01 (0, 9.51)), (15.97 ± 0.18) with a mean difference (SE) of −1.06 (0.58) (p = 0.06) suggesting recall of 1.06 more words after a 20-30 minute delay. Higher consumers had a lower GDS score (1.77 ± 3.73) compared to lower consumers (3.73 ± 1.77), p = 0.01. Spot the word test scores (assesses premorbid verbal abilities using a robust lexical decision task) were higher for high anthocyanin consumers (53.06 ± 4.38) compared to lower consumers (50.40 ± 4.38), mean difference (SE) = −2.66 (1.10), p = 0.01, meaning participants with higher intake of dietary anthocyanin were able to point at 2.7 more real words than low consumers. Dietary consumption of anthocyanin in older adults with MIS is associated with beneficial effects on depressive scores and the ability to retrieve words. Further research is warranted to identify optimal dosage for recommended intake. This cross-sectional study used baseline data from a randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ANZCTR):12622000065796.

Health literacy, but not memory, is associated with hippocampal connectivity in adults with low levels of formal education.

The influence of hippocampal connectivity on memory performance is well established in individuals with high educational attainment. However, the role of hippocampal connectivity in illiterate populations remains poorly understood. Thirty-five illiterate adults were administered a literacy assessment (Test of Functional Health Literacy in Adults [TOFHLA]), structural and resting state functional magnetic resonance imaging, and an episodic memory test (Free and Cued Selective Reminding Test). Illiteracy was defined as a TOFHLA score < 53. We evaluated the correlation between hippocampal connectivity at rest and both free recall and literacy scores. Participants were mostly female (57.1%) and self-declared as being Black individuals (84.8%), with a median age of 50 years. The median TOFHLA literacy score was 28.0 [21.0; 42.5] out of 100 points and the median free recall score was 30.0 [26.2; 35] out of 48 points. The median gray matter volume of both the left and right hippocampi was 2.3 [2.1; 2.4] cm3. We observed a significant connectivity between both hippocampi and the precuneus and the ventral medial prefrontal cortex. The right hippocampal connectivity positively correlated with the literacy scores (β=0.58, P=0.008). There was no significant association between episodic memory and hippocampal connectivity. Neither memory nor literacy scores correlated with hippocampal gray matter volume. Low literacy levels correlated with hippocampal connectivity in illiterate adults. The lack of association with memory scores might be associated with low brain reserve in this sample. A significant link was found between health literacy and hippocampal connectivity.Enhanced hippocampus- ventromedial prefrontal cortex connectivity suggests potential cognitive reserve improvement.Higher cognitive reserve may protect against hippocampal atrophy and neurodegeneration.Health literacy improvements could help prevent cognitive impairment in illiterate populations.Study highlights importance of considering structural racism in brain connectivity research.

Enhanced memory and hippocampal connectivity in humans 2 days after brief resistance exercise.

Exercise has significant health benefits and can enhance learning. A single bout of high-intensity resistance training may be sufficient to improve memory. This study aimed to assess memory enhancement by a single bout of high-intensity resistance training and to examine the neural underpinnings using resting-state functional magnetic resonance imaging (MRI). Sixty young adults (34 men and 26 women), divided into the training and control groups, participated. The first session included verbal memory recall tests (cued- and free-recall), resting-state functional MRI (rs-fMRI), and a single-bout high-intensity resistance training for the training group. Two days later, they underwent post-intervention memory tests and rs-fMRI. The study design was 2 groups×2 sessions for memory tests, and within training group comparisons for rs-fMRI. Compared to the control group without resistance training, the training group showed higher cued-recall performance 2 days after the brief resistance training (training: +0.27, control: -0.13, interaction: p=.01), and their free-recall scores were associated with enhanced left posterior hippocampal connectivity (r=.64, p<.001). These results suggest that brief high-intensity resistance exercise/strength training could enhance memory without repeated exercising. The quick effect of resistance training on memory and hippocampal connectivity could be revealed. A focused and one-shot exercise may be sufficient to enhance memory performance and neural plasticity in a few days.

Plasma p-tau181 as an outcome and predictor of multidomain intervention effects: a secondary analysis of a randomised, controlled, dementia prevention trial.

It is unknown whether multidomain interventions, which might preserve late-life cognition, affect Alzheimer's disease pathology. Previous studies measured cerebrospinal fluid and imaging Alzheimer's disease biomarkers in small subsamples of multidomain trial participants. Newly developed assays enable the measurement of blood-based Alzheimer's disease biomarkers in larger samples. We aimed to assess whether plasma tau phosphorylated at threonine 181 (p-tau181) was able to detect or predict 3-year multidomain intervention effects. This is a secondary analysis of the randomised, controlled, Multidomain Alzheimer Prevention Trial (MAPT) testing a 3-year multidomain intervention, omega-3 fatty acid supplementation, or both versus placebo, in individuals aged 70 years and older in 13 memory centres in France and Monaco. Plasma p-tau181 was measured in stored blood samples in a subsample of 527 participants on an intention-to-treat basis. Changes in cognitive score were calculated as a composite measure using the average of Z scores for the following tests: Mini Mental State Examination orientation items, Free and Cued Selective Reminding Test (sum of free and total recall scores), category fluency, and Digit Symbol Substitution Test. Intervention effects on 3-year change in p-tau181 concentration were estimated by use of a linear mixed model with centre-specific random intercepts. Recruitment took place between May 30, 2008, and Feb 24, 2011. Median baseline plasma p-tau181 was 8·8 pg/mL (IQR 6·7-11·9) in the total sample, and significantly higher in older individuals, men, APOE ε4 carriers, and participants with renal dysfunction or a positive PET amyloid scan. During 3-year follow-up, individuals with raised baseline p-tau181 underwent greater cognitive decline (eg, mean difference in 3-year change on the composite cognitive score between control group participants with normal and abnormal baseline levels of p-tau was -0·34 [effect size -0·52; 95% CI -0·61 to 0·07] in the fully adjusted model using a 12·4 pg/mL cutoff for abnormal baseline p-tau181), but there were no intervention effects on change in p-tau181 either in this subgroup or the total population, and no effect on cognitive change in individuals with raised baseline p-tau181 (eg, in the fully adjusted model using the 12·4 pg/mL cutoff for p-tau181 abnormality, the mean difference [95% CI] in this subgroup in 3-year decline on the composite cognitive score between the control group and the multidomain + omega-3 group, the omega-3 group, and the multidomain intervention group, was, respectively: 0·13 [-0·21 to 0·47], 0·03 [-0·30 to 0·36], and 0·10 [-0·26 to 0·46]). Surprisingly, individuals with raised baseline p-tau181 showed a decrease in p-tau181 during follow-up (eg, unadjusted mean [95% CI] 3-year change was -3·01 pg/mL (-4·45 to -1·56) in control group subjects with abnormal baseline p-tau181 [using the 12·4 pg/mL abnormal p-tau cutoff]). Our results support the utility of p-tau181 as a prognostic biomarker, but it did not predict or detect intervention effects in this study. Further investigation of its usefulness as a prevention trial outcome measure is required. Toulouse Gérontopôle, French Ministry of Health and Pierre Fabre Research Institute.

Normative data for the Spanish versions of the CVLT, WMS-Logical Memory, and RBMT from a sample of middle-aged and old participants.

Episodic memory (EM), one of the most commonly assessed cognitive domains in aging, is useful for identifying pathological processes such as mild cognitive impairment and dementia. However, EM tests must be culturally adapted, and the influence of sociodemographic variables analyzed, to provide cut-off points that enable correct diagnosis. The aim of this article is to report updated Spanish normative data for three EM tests: the California Verbal Learning Test, the Logical Memory subtest of the Wechsler Memory Test, and the Rivermead Behavioral Memory Test. Measures include immediate, short-, and long-delay free recall, intrusions, and global scores. The entire sample is comprised of 1,193 cognitively unimpaired participants aged +50, recruited from three cohort studies within the Spanish Consortium for Ageing Normative Data. Participants who subsequently developed cognitive impairment, detected at follow-up, were removed from the total sample. Data analysis included transformation of percentile ranges into scalar scores, tests for the effects of education level, age, and sex on performance, and linear regression to calculate scalar adjustments. Tables with percentile ranges and scalar scores for each measure are provided, with adjustments for age, education level, and sex, as required. The normative scores provide robust data for assessing EM in Spanish middle-aged and old populations. Effects of sex, age, and education level in each measure are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Verbal episodic memory in children undergoing temporal lobe epilepsy surgery: a one-year follow-up study.

Verbal episodic memory (VEM) is often unimpaired in children with focal epilepsy undergoing left temporal lobe resections, unlike what we might expect in the adult brain. The latter findings suggest that epileptiform activity in early life disrupts memory system lateralization, leading to the development of bilateral memory representation. The present study aims to analyze whether the laterality of epilepsy is a major predictor for post-operative VEM prognosis in pediatric temporal lobe epilepsy (TLE) surgery. This research also pretends to provide evidence about the relationship of VEM performance with other relevant demographical and clinical factors such as sex, age at onset of seizures, age at surgery and duration of epilepsy, as well as to study the impact of presurgical VEM performance on postsurgical outcomes. Pre-operative and one-year follow-up post-operative word-list recall scores from 25 children who underwent TLE surgery (left-sided, n = 11; right-sided, n = 14) were extracted from the Hospital Sant Joan de Deu database and were retrospectively analyzed. No significant presurgical intergroup differences were found when comparing VEM scores by laterality of epilepsy (p > 0.5). Looking at the left TLE group, a high negative correlation was found between the onset age and the pre-operative long-term free recall score (rho = -0.72, p = 0.01). No significant pre- to post-operative intragroup changes were found regarding VEM performance, regardless of epilepsy laterality (left TLE group, p > 0.56; right TLE group, p > 0.12). The laterality of epilepsy does not show to be a significant factor in and of itself regarding presurgical VEM outcome and its prognosis one year after surgery, thus supporting the bilateral memory representation hypothesis. Furthermore, a younger age at onset of seizures seems to be related with a better pre-operative VEM performance, likely due to a more efficient reorganization of memory system induced by a greater brain plasticity at lower ages; however, this relationship has been only reported for the left-sided epilepsies in our sample.

The Memory Binding Test: a new tool to assess emerging episodic memory decline in asymptomatic at‐risk individuals to Alzheimer’s disease

AbstractBackgroundEpisodic memory (EM) deficits are a hallmark of Alzheimer’s disease (AD). The Free and Cued Selective Reminding Test (FCSRT) is the most specific official diagnostic tool detecting AD‐linked EM alterations in advanced preclinical stages (Grober et al., 2021). However, new tools that anticipate diagnosis to the at‐risk phase are needed, to reach more meaningful therapies. Based on existing research, we aim to investigate the Memory Binding Test (MBT) promising capacity to detect the appearance of subtle AD‐linked EM alterations and anticipate AD‐diagnosis to an at‐risk phase (Bushcke ey al., 2017; Mowrey et al., 2018).MethodsFCSRT and MBT scores were collected yearly during 5 years from the INSIGHT‐preAD cohort. We selected 3 groups controlled for age, education level, gender, beta‐amyloid burden (AB+), and neurodegeneration status based on 15 individuals who converted to prodromal‐AD during follow‐up, as follows: converters/AB+; non‐converters/AB+; controls/AB‐. Evaluation of both list‐learning tests is mainly based on free recall (FR) and total (cued) recall (TR) scores. The FCSRT uses 1‐list of words to remember while the MBT uses 2‐lists, introducing a binding component sensitive to subtle EM alterations. Data was analysed using mixed effect models including age, gender, and education as covariates.ResultsWhen compared with the FCSRT, the MBT anticipated the detection of AD‐linked EM alterations in the converters/AB+ versus the other groups. In the MBT decline started up to 5 years prior to diagnosis, in delayed FR (mainly associated to executive dysfunction), followed by decline in 4 binding‐associated scores 1 year later (linked to storage deficits associated with the amnesic hippocampal syndrome characteristic of AD). Therefore, at an at‐risk phase, MBT outperformed FCSRT, both in the year of diagnosis and in the number of scores confirming AD‐linked EM deficits.ConclusionWe show the MBT capacity to detect the initial subtle EM alterations and to anticipate diagnosis to the at‐risk phase, while participants remain cognitively normal. We argue that the MBT (at‐risk phase detection) and the FCSRT (preclinical phase classification) could be complementary rather than concurrent tools, fostering meaningful innovative treatments to prolong quality of life in AD, a disease that remains without a cure.

The RESIST Study: Do TNF Inhibitors Protect Against Cognitive Decline in Rheumatoid Arthritis Patients With Mild Cognitive Impairment?

AbstractBackgroundRheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation in the joint synovium. Considering growing research interest into the role that systemic inflammation might play in the pathogenesis of Alzheimer’s disease (AD), studying cognitive decline in RA patients can provide important insights into the potential effects of inflammation on cognitive health. Furthermore, evidence suggests that biological drugs used to treat RA, specifically TNF inhibitors (TNFi), may protect against AD progression by reducing systemic inflammation. The rheumatoid arthritis medication and memory study (RESIST) is a multicentre longitudinal observational study which aims to compare rates of cognitive decline in adults with both RA and mild cognitive impairment who are on either a conventional synthetic disease modifying anti‐rheumatic drug (csDMARD) or a TNFi.Method251 participants were recruited (160 on csDMARDs, 91 on TNFis). Participants completed assessments at six‐month intervals for eighteen months. The primary outcome was performance on the Free and Cued Selective Reminding Test (FCSRT). It was hypothesised that the rate of decline in FCSRT score would be lower among participants taking TNFis.ResultBetween‐groups ANCOVA was conducted to compare mean FCSRT scores at 12/18 months, adjusting for baseline score, age, disease activity, pain, wellbeing, depressive symptoms and physical function. Results showed that neither group declined in FCSRT free recall score on average over the 18 month follow‐up period, and that there was no significant difference between groups at 12 (mean difference = 0.59, 95% CI = ‐1.54, 2.72) or 18 months (mean difference = 1.24, 95% CI = ‐0.99, 3.47).ConclusionThe absence of decline in FCSRT performance in either group was unexpected. These findings raise the possibility that both csDMARDs and TNFis may protect against cognitive decline However, a major limitation of the study was attrition due to the COVID‐19 pandemic, which may have influenced results – those who experienced a greater degree of cognitive decline may have been more likely to withdraw from the study. Additional planned analyses will examine the potential moderating effect of APOE genotype, and the relationship between peripheral serum C reactive protein, cytokine levels and cognitive outcomes.

CASBA neurological assessment: Noninvasive EEG biomarkers classify amyloid‐PET, clinical diagnosis, cognitive dementia rating, and FCSRT free recall scores in patients with cognitive decline

AbstractBackgroundAlzheimer’s Disease (AD) is difficult to diagnose and stage, often relying on burdensome clinical tests for neural protein aggregation and cognitive performance. Delays and errors in the accurate diagnosis of AD reduce patient outcomes and prevent early therapeutic intervention. The CASBA electroencephalography (EEG) system leverages a custom sequence of dynamic visual stimuli to elicit and translate novel and noninvasive neural signals biomarkers into accurate estimates of amyloid burden, cognitive performance, and clinical diagnosis, to facilitate clinical decision‐making in patients with cognitive decline.MethodIn a board‐approved study, human patients with mild cognitive impairment (MCI; 71.2 ± 8.2 years old), subjective cognitive decline (SCD; 70.7 ± 6.3 years old), and AD diagnosis (71.2 ± 6.6 years old), alongside amyloid PET (Anti‐Serum Amyloid P Antibody), cognitive testing (i.e. FCSRT), and clinical dementia rating (CDR). Neural signals were collected on a 64‐channel equidistant EEG system (2048Hz, Ag/AgCl; ANT Neuro, Enschede)]. Automated preprocessing and machine learning classification pipelines were developed to extract EEG features and calculate estimates of physiological and cognitive AD metrics from these EEG biomarkers.ResultCASBA accurately classified normal vs. subnormal FCSRT free recall score (threshold of 18, 77.3% balanced accuracy, 84.0% specificity, 70.6% sensitivity), SCD v. MCI/AD clinical diagnosis (79.4% balanced accuracy, 77.3% specificity, 81.5% sensitivity), CDR (threshold of 1, 79.2% balanced accuracy, 76.9% specificity, 81.5% sensitivity), and amyloid‐PET (composite threshold of 1.25, 83.0% balanced accuracy, 75.0% specificity, 91.9% sensitivity).ConclusionThe CASBA neurological assessment accurately predicts important clinical data including patient diagnosis and staging, amyloid burden, and performance on key evaluations of cognition in AD. CASBA supports physician decision making and patient stratification and suggests a new method for noninvasive tracking and repeat assessment during clinical trials. As such, the CASBA neurological assessment offers a promising new tool to advance clinical care and innovation for patients with neurodegenerative disease.

Pre-reading activities may reduce processing demands in working memory

Reading research has found that pre-reading activities positively affect comprehension, which might also act as a tool to reduce the processing demands in working memory (ROSCIOLI; TOMITCH, 2022). The present study investigated whether there was a correlation between pre-intermediate and advanced Brazilian EFL students’ working memory capacity as measured by the Reading Span Test and their results obtained in comprehension tests after receiving treatment with two pre-reading activities: Contextual Redefinition and Graphic Organizer (MOORE; READENCE; RICKELMAN, 1999). The former focused on building vocabulary, whereas the latter targeted the organizational pattern of the text. There were two dependent measures: written free recall and comprehension questions. We hypothesized that the treatments would change the correlations between readers’ working memory capacity and task performance. Specifically, we expected the correlations between reading span and comprehension to be smaller in the treatment conditions compared to the control. The findings reveal that the activities can affect reading comprehension differently depending on students’ proficiency. The correlations between reading span and comprehension questions scores were smaller when advanced participants received treatment with the Contextual Redefinition. Conversely, there was an increase in the correlations between reading span and written free recall scores when the pre-intermediate group received treatment with the same pre-reading activity. Also, there was a decrease in the correlations between reading span and written free recall scores when pre-intermediate participants received treatment with the Graphic Organizer. Altogether, the Contextual Redefinition reduced processing demands for the advanced participants, whereas the Graphic Organizer did the same for the pre-intermediate group.

47 Amyloid/Tau Ratio and Early Predictors of Alzheimer's Disease

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.

6 The Moderating Role of Physical Activity on Hippocampal Iron Deposition and Memory Outcomes in Typically Aging Older Adults

Objective:Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.Participants and Methods:62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.Results:Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p &gt; 0.05) or interact with physical activity on verbal memory outcomes (p &gt; 0.05).Conclusions:Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.

Cognitive Profile in Parkinson’s Disease Dementia Patients with Low versus Normal Cerebrospinal Fluid Amyloid Beta

Introduction: In patients with Parkinson’s disease (PD), low cerebrospinal fluid (CSF) amyloid beta 1-42 (Ab42) at baseline is the most consistent CSF biomarker as a risk factor for developing dementia. Low CSF Ab42 is, however, a typical hallmark of Alzheimer’s disease (AD). Hence, low CSF Ab42 in patients with PD may indicate presence of comorbid AD pathology and may predict a more AD-like cognitive profile when they develop dementia. Our study aimed to investigate if low CSF Ab42 at baseline is associated with a more AD-like cognitive profile in PD patients with dementia. Methods: In a prospectively followed-up, population-based cohort of newly diagnosed PD patients, we compared the cognitive profile of dementia in those with a low CSF Ab42 level at baseline with that of patients who had normal levels at the time when they developed dementia. Four different cognitive domain z-scores (memory, attention, executive, visuospatial) were calculated. Patients were subdivided into three tertiles or categorized dichotomously based on the baseline CSF Ab42 levels as measured by electrochemiluminescence and ELISA. Results: During 10-year follow-up, 37 patients met the inclusion criteria. Memory domain composite z-scores, memory subtest z-scores, and the difference between long-delay free recall versus recognition scores were not significantly different between the groups. Composite z-scores of visuospatial functions significantly differed between the tertiles, which was not significant after Bonferroni correction. In the dichotomous group analysis, z-scores of visuospatial functions significantly differed between the two groups. The other cognitive domain z-scores were not significantly different. Conclusions: In patients with PD dementia, low CSF Ab42 level at baseline is not associated with a specific cognitive profile.

Verbal memory depends on structural hippocampal subfield volume.

To investigate correlates in hippocampal subfield volume and verbal and visual memory function in patients with temporal lobe epilepsy (TLE), mild amnestic cognitive impairment (MCI) and heathy participants (HP). 50 right-handed participants were included in this study; 11 patients with temporal lobe epilepsy (TLE), 18 patients with mild amnestic cognitive impairment (MCI) and 21 healthy participants (HP). Verbal memory performance was evaluated via the verbal memory test (VLMT) and visual memory performance via the diagnosticum for cerebral damage (DCM). Hippocampal subfield volumes of T1-weighted Magnetic Resonance Imaging (MRI) scans were computed with FreeSurfer version 7.1. Stepwise correlation analyses were performed between the left hippocampal subfield volumes and learning, free recall, consolidation and recognition performance scores of the VLMT as well as between right hippocampal subfield volumes and visual memory performance. The volume of the left subicular complex was highly correlated to learning performance (β = 0.284; p = 0.042) and free recall performance in the VLMT (β = 0.434; p = 0.001). The volume of the left CA3 subfield showed a significant correlation to the consolidation performance in the VLMT (β = 0.378; p = 0.006) and recognition performance in the VLMT (β = 0.290; p = 0.037). There was no significant correlation identified between the right hippocampal subfields and the visual memory performance. The results of this study show verbal memory correlates with hippocampal subfields and support the role of left subiculum and left CA2/CA3 in verbal memory performance.

Motivational and cognitive predictors of apathy after subthalamic nucleus stimulation in Parkinson's disease.

Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1 year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy.

Impact of MCI on testing performance in different cognitive domains

AbstractBackgroundImpaired memory affects cognitive testing performance. This study examined in elderly adults the impact of mild cognitive impairment (MCI) on testing performance in different cognitive domains.MethodAfter giving their IRB‐approved written consent, 10 cognitively normal subjects (65±2 years old) and 10 patients with amnestic MCI (68±2 years old) completed the Mini‐Mental State Examination (MMSE), Digit‐Span test, California Verbal Leaning Test –2nd edition (CVLT‐II), and Trail Making Test – B version (TMT‐B). Cognitive performances of the MCI and normal groups were compared by standard t tests. ANOVA was applied to evaluate the impacts of the group and trial‐number factors on immediate Free‐Recall (FR) performance in CVLT‐II.ResultThe group MMSE scores were 24.8±0.4 in the MCI group vs 29.2±0.3 in the normal subjects (P&lt;0.0001). The time to complete TMT‐B was prolonged markedly in the MCI (154±28 s) vs. normal (56±6 s) subjects (P = 0.007). Forward performance score in the Digit‐Span test did not differ between the groups (MCI 9.0±0.6 vs normal 8.5±0.9), although backward Digit‐Span performance was superior (P = 0.021) in the normal (7.0±0.6) vs. MCI (5.1±0.4) groups. CVLT‐II immediate FR scores improved with successive trials in both MCI and normal subjects (trial‐number factor P&lt;0.0001). Although the FR scores from the first 2 trials did not differ between the groups, there was a significant difference appeared in the FR scores of the 3rd and the overall FR scores were appreciably lower in the MCI subjects (group factor P = 0.006). Moreover, 30‐sec Short‐Delay (S‐D) and 10‐min Long‐Delay (L‐D) FR scores were significantly lower in the MCI subjects (Table).ConclusionBoth short‐term memory and visuospatial‐executive function were significantly impaired in the MCI patients as compared with the age‐matched cognitively normal cohort. Repeated trials improve the immediate Free‐Recall in both groups. The backward Digit‐Span test was more sensitive than the forward test to detect the impairment of short‐term memory and attention in the elderly adults with MCI.

Differences in learning retention and experience of augmented reality notes compared to traditional paper notes in a chiropractic technique course: A randomized trial.

To investigate if a written guide or augmented reality (AR) guide improves free recall of diversified chiropractic adjusting technique and to capture participants' impressions of the study in a poststudy questionnaire. Thirty-eight chiropractic students were evaluated for diversified listing (a nomenclature denoting vertebral malposition and correction) recall, pre-AR and post-AR, or written guide review. The vertebral segments used were C7 and T6. Two randomized groups reviewed an original course written guide (n = 18) or a new AR guide (n = 20). A Wilcoxon-Mann-Whitney (C7) and t test (T6) compared group differences in reevaluation scores. A poststudy questionnaire was given to capture participants' impressions of the study. Both groups showed no significant differences in free recall scores after reviewing the guides for C7 or T6. The poststudy questionnaire suggested a number of strategies could be used to improve current teaching material such as more detail in the written guides and organizing content into smaller blocks. Use of an AR or written guide does not seem to change participants' free recall ability when used to review diversified technique listings. The poststudy questionnaire was useful to identify strategies to improve currently used teaching material.