Complex Figure Research Articles

Clinical Manifestations.

Accelerated Long-term Forgetting (ALF) is the phenomenon whereby material is retained normally over short intervals (minutes or hours) but forgotten abnormally rapidly over longer periods (days or weeks). ALF may be an early marker of cognitive decline, but little is known about its relationships with preclinical Alzheimer's disease pathology in older adults, and how memory selectivity may influence which material is forgotten. Participants in 'Insight 46', a sub-study of the MRC National Survey of Health and Development (British 1946 birth cohort), completed cognitive and neuroimaging assessments at two time-points (baseline at age ∼70; follow-up ∼2.4 years later). At follow-up, we assessed Complex Figure Drawing (copy; immediate recall; 30-minute recall; 7-day recall). Complex Figure items were categorized as 'outline' or 'detail' (Fig1), to test the hypothesis that forgetting the outline of the structure would be more sensitive to the effect of brain pathologies. ALF scores were calculated as the proportion of material retained after 7 days, relative to 30 minutes. Rates of cerebral atrophy between baseline and follow-up were quantified from T1-weighted MRI using the Brain Boundary Shift Integral (BBSI). β-amyloid status (positive/negative) was determined from 18F-Florbetapir-PET. Baseline serum neurofilament light (NfL) was quantified (Quanterix Simoa assay). Multivariable regression models were used to investigate the effects (mutually adjusted) of β-amyloid status, BBSI and NfL on ALF in n = 316 clinically-normal individuals (50% female; 22% β-amyloid positive; 30% APOE-ε4 carriers), and to explore interactions between these predictors, adjusting for potential confounders including prospectively-collected childhood cognitive ability and education. 'Outline' items were better retained than 'detail' (Fig1). β-amyloid-positive participants had poorer ALF scores for 'outline' (but not 'detail') items (Fig1C; Table 1). Unexpectedly, higher NfL was associated with scores for 'outline' items (Table 1). Greater rate of cerebral atrophy predicted poorer retention among participants with elevated β-amyloid and higher NfL (Table 1; Fig2). These results provide evidence of associations between biomarkers of brain pathologies and ALF in 73-year-olds. Interactions between different biomarkers merit further exploration. ALF may be a sensitive outcome measure for therapeutic trials in preclinical AD. Better retention of 'outline' (vs. 'detail') items illustrates the strategic role of memory selectivity.

Neuropsychological Characteristics of Wandering in Patients with Drug‐naïve Alzheimer’s Disease

AbstractBackgroundWandering represents one of a major problem occurring in patients with Alzheimer’s disease (AD). To find the disproportionate neuropsychological deficit and behavioral psychological symptoms in dementia (BPSD) of AD patients with wandering compared to AD patients without wandering, this study examined the set of neuropsychological tests and caregiver‐administered neuropsychiatric inventory (CGA‐NPI).MethodsPsychotropic‐naïve (drug‐naïve) probable AD patients with wandering (64) and without wondering (278) were assessed with the Seoul Neuropsychological Screening Battery, which included measures of memory, intelligence, and executive functioning.ResultsPatients with wandering had lower scores in the Rey‐Osterrieth Complex Figure copy, Fist‐edge‐palm, Alternating hand movement tests compared to patients without wandering. The degree of wandering in AD patients was significantly related with CGA‐NPI subdomains of aggression, disinhibition, depression, and delusions.ConclusionsThis study showed that 1) AD patients with wandering have disproportionately cognitive deficit suggesting frontal and right parietal dysfunctions, 2) wanderings are related with specific BPSD. Considering these results, AD patients with wandering may have specific neuronal anatomic substrates related with pathology of Alzheimer.

Insomnia and Neurocognitive Functioning in Cognitively Healthy Older Adults

AbstractBackgroundInsomnia is the most common sleep disorder in older adults, affecting the ability to fall and stay asleep for approximately 15‐35% of aging adults (Buysse et al., 2011). Additionally, sleep fragmentation and disordered sleep are well‐established symptoms of Alzheimer’s disease (AD). Patients and their caregivers frequently find these sleep changes distressing; however, the relationship between insomnia and preclinical Alzheimer’s disease remains unclear. The purpose of the present study is to compare performance on neurocognitive measures between cognitively healthy older adults with and without clinician‐determined insomnia to assess whether insomnia acutely impacts cognitive functioning.MethodData were obtained from the National Alzheimer’s Coordinating Center (NACC) database. As part of ongoing data collection, NACC participants completed surveys and underwent a neuropsychological evaluation. Participants who were cognitively healthy at baseline, reported insomnia status, and were at least 65 years of age were included (N = 3,733). Clinicians determined the presence of insomnia (present/absent). A series of Welch’s t‐tests were used to compare insomnia status groups on demographic factors (age, educational attainment, and sex) as well as neurocognitive measures typically related to Alzheimer’s disease (animal and vegetable fluency, letter fluency, Trail‐Making Test, Benson Complex Figure delayed recall, Montreal Cognitive Assessment delayed recall).ResultPreliminary analyses of sample characteristics found evidence that individuals with insomnia were older than those without insomnia (t(784.11) = 2.046, p = 0.041). As expected, clinician‐determined insomnia was more common in men than women (χ2 (1) = 29.638, p < .001). Group comparisons indicated no cross‐sectional relationship between insomnia status and neurocognitive measures (all p >.05, all d ≤ .06).ConclusionDisordered sleep is often seen in Alzheimer’s disease, yet the nature and timing of this relationship are unclear. We found no association between insomnia status and neurocognitive performance in a large, cross‐sectional sample of healthy older adults. It is possible that sleep disturbance is not a preclinical symptom of AD but instead may emerge closer to or following AD diagnosis. Alternatively, the nature of the disordered sleep may not be related to insomnia per se but could reflect difficulty sleeping during the night and remaining awake during the day.

Severity of HIV-associated neurocogtitive disordes and performance at the Rey-Osterrieth Complex figure

Severity of HIV-associated neurocogtitive disordes and performance at the Rey-Osterrieth Complex figure

Syntactic processing skills in elderly people with mild cognitive impairment and mild Alzheimer’s disease

AbstractBackgroundCommunication and language impairments may be found in individuals with CCL. Thus, a better understanding language processing in this group and in healthy aging is necessary. Most studies in CCL and AD have focused on naming and semantic processes, and few studies have focused on syntactic processing skills, especially in the Brazilian population.MethodA total of 114 elderly people of both sexes, aged at least 60 years, living in the city of São Paulo, were evaluated. The subjects were divided into 32 healthy elderly, 22 with aminestic mild cognitive impairment, 43 with non‐aminestic mild cognitive impairment and 17 with mild Alzheimer’s disease. For language assessment, the Grammar Reception Test – TROG2 was used as the main instrument, as well as the tests Northwestern Anagram Test, Token Test and the Object and Verb Naming Battery. For cognitive evaluation using the tests and functionality, the following tests were used: MoCA, Rivermead Behavioral Memory Test, Tracks A and B Test, Rey‐Osterrieth Complex Figure Test, Stroop Test, Digit Extension Test, Learning Test Verbal de Rey FAS, Three Words Three Shapes Test. The functionality of the was assessed using the Lawton & Brody scale for Activities of Daily Living.ResultOur results showed differences in performance among the control, CCL, and AD groups in the total number and the profile of correct answers according to the type of sentence tested (p<0.05). Sentences with zero anaphora structure discriminated the control group from CCLa and AD, as well as CCLna from AD; pronoun gender/number sentences discriminated controls from CCLa (p<0.05). These sentence types bring to evidence the effect of increased demand on working memory and executive functions on syntactic processing.ConclusionThe use of the Grammar Reception Test ‐ TROG ‐ 2 instrument can be useful in the assessment of the elderly, serving as a reference to differentiate healthy aging from cognitive and language impairments. Patients with MCI already have difficulties in syntactic processing when syntactic complexity is increased, overloading working memory and executive functions. These difficulties are intensified in patients with AD.

P71: Predicting amyloid-ß deposition status in amnestic mild cognitive impairment using neuropsychological profiles.

Objective:Previous studies investigating neuropsychological profiles of cognitive impairment people have found a learning curve can be a useful indicator of AD diagnosis or progression. However, the data on the relationship between amyloid β (Aβ) deposition status and the learning curve in amnestic mild cognitive impairment (aMCI) are limited. In this study, we investigate the role of the learning curve in predicting Aβ deposition status in patients with aMCI.Methods:This is a cross-sectional study of 67 aMCI patients (N = 67; 33 aMCI with amyloid positive (Aβ-PET (+)), and 34 aMCI with amyloid negative (Aβ-PET (-))). All participants underwent Seoul Neuropsychological Screening Battery for a comprehensive neuropsychological test battery and brain MRI. To determine Aβ deposition status, each participant underwent amyloid PET scans using 18F-florbetaben. The learning curve was obtained using immediate recall of Seoul Verbal Learning Test-learning curve (SVLT- learning curve). The association of cognitive test scores and dichotomized Aβ deposition status was examined using logistic regression models in patients with aMCI. Receiver operating characteristic (ROC) curves were used to examine the predictive ability of cognitive test to detect Aβ deposition status in aMCI.Results:Logistic regression models showed that SVLT-learning curve and Rey Complex Figure Test- delayed recall (RCFT-delayed recall) scores were significantly associated with Aβ deposition status. In ROC analysis to assess the predictive power, SVLT-learning curve (area under the curve (AUC) = 0.734, P = 0.001) and RCFT-delayed recall (AUC = 0.739, P = 0.001) independently discriminated Aβ-PET (+) and Aβ-PET (-). The combination of these clinical markers (SVLT-learning curve and RCFT-delayed recall) improved the predictive accuracy of Aβ-PET (+) (AUC = 0.833, P < 0.001).Conclusions:Our findings of association of Aβ deposition status with SVLT-learning curve and RCFT- delayed recall suggest that these cognitive tests could be a useful screening tool for Aβ deposition status among aMCI patients in resource-limited clinics.

Analysis of multi‐dimensional cognitive function of different sexes in the middle‐aged and elderly people at high altitude

AbstractBackgroundTo explore the overall and multi‐dimensional cognitive function of middle‐aged and elderly people and gender difference analysis of its influencing factors under hypoxia environment.MethodFrom January 2018 to December 2021, using cross‐sectional study design, all participants from Xining, Qinghai Province (with an average altitude of 2,500m) who have lived for more than 20 years were selected.General data questionnaire survey, laboratory collection, overall and multi‐dimensional cognitive function assessment were conducted.ResultA total of 500 middle‐aged and elderly people were included in this study, 299 males and 201 females, with an average age of 64.17 ± 10.58 years. Compared with women, there were more men working in civil service, earning more than 5000 months, smoking and drinking, accompanied by hypertension and diabetes (P<0.01, P<0.001), but Geriatric Depression Scale(GDS)and Pittsburgh sleep quality index (PSQI) scores were significantly lower (P<0.01).Compared with women’s multiple cognitive domains, scores of Mini mental state examination(MMSE), Complex Figure Test Delay Recall(CFT‐DR), Digit Span Forward(DSF) and Digit Span Backward(DSB) in men were higher (P<0.05, P<0.01), while scores of Trail Making Test (TMT‐A and TMT‐B) were significantly lower (P<0.01, P<0.001).The neutrophil lymphocyte ratio (NLR) and homocysteine (HCY) in peripheral blood were higher than those in women (P<0.05, P<0.01). Covariance analysis showed after adjusting for education level that scores of MMSE and situational memory (CFT‐DR) of men in different age groups were higher than those of women, while scores of attention (TMT‐A) and executive ability (TMT‐B) were lower than those of women (P<0.05, P<0.01). After adjusting for age, scores of MMSE and CFT‐DR of men in primary school, middle school and high school were higher than those of women (P<0.05, P<0.01). With the influence of education level, men’s TMT‐A scores showed a trend of lower (P<0.05, P<0.01), while women’s TMT‐A scores changed little.TMT‐B score of men was lower than that of women in the four education stages (P<0.05), but there was no trend for men and women to optimize with the increase of education level.ConclusionMiddle‐aged and elderly people of different sexes living in high altitude hypoxic environment may have different multidimensional cognitive decline.

Clinical Manifestations.

Episodic memory impairment is a widely known core clinical symptom of Alzheimer's disease (AD). However, it is still uncertain if it is possible to detect meaningful signs or changes in memory in the preclinical stage of AD due to their within-normal-range performance. In the current study, we investigated both verbal and visuospatial memory as markers to track the disease progression in the preclinical AD. We selected cognitively normal (CN) participants from the Gwangju Alzheimer's Disease and Related Dementia Cohort in Korea. We included a group of CN individuals who showed a significant amyloid-beta (aß) deposition, defined by amyloid PET, at baseline and completed at least two follow-up evaluations. In the final analysis, we included 130 individuals in the preclinical stage of AD. Episodic memory measures were delayed recall scores from the Rey Complex Figure Test (RCFT_delayed) and Seoul Verbal Learning test (SVLT_delayed). We performed logistic regression analysis with stepwise selection to examine associations between memory tests and progression. The mean follow-up month was 36.21. Twenty-one (16.2%) participants were converted to MCI (n = 19) or AD dementia (n = 2), while the rest stayed as CN. When both RCFT_delayed and SVLT_delayed at baseline were entered in the logistic regression model, only the RCFT_delayed was significantly associated with the progression (OR = 0.288; 95% CI, 0.138-0.602; p = 0.001). When change scores were added to the model, RCFT_delayed at baseline (OR = 0.223; 95% CI, 0.101-0.496; p < 0.001), RCFT_delayed change score (OR = 0.470; 95% CI, 0.258-0.857; p = 0.014), and SVLT_delayed change score (OR = 0.523; 95% CI, 0.290-0.942; p = 0.031), were significant. Our results suggest that visuospatial, not verbal, memory measures may play an important role in sensitively detecting the relevant sign of future progression in asymptomatic individuals. In terms of verbal memory, the longitudinal decline was associated with progression. Our study suggests that the inclusion of a visuospatial memory test and repeated evaluation can help to detect the earliest decline in the preclinical stages of AD.

The multidomain intervention trial for prevention of dementia among older adults with type 2 diabetes: a multi‐center, randomized, 18‐month controlled trial

AbstractBackgroundThe aim of the Japan‐Multidomain Intervention Trial for Prevention of Dementia in Older Adults with Diabetes (J‐MIND‐Diabetes) was to examine the efficacy of multi‐domain intervention in prevention of cognitive decline in older adults with type 2 diabetes and mild cognitive impairment (MCI).MethodThe J‐MIND‐Diabetes is an 18‐month, multi‐centered, randomized controlled trial. Outpatients with type 2 diabetes aged 70‐85 years with MCI were recruited and randomized into multi‐domain intervention (management of metabolic and vascular risk factors, physical exercise, nutritional guidance, and promotion of social participation) and control groups (general instructions on dementia prevention) at a 1:1 allocation ratio using the stratified permuted‐block randomization methods. The primary outcome was a change from baseline to 18‐month follow‐up in a global composite score combining several neuropsychological tests, which include the MoCA‐J, the MMSE, the Rey‐Osterrieth Complex Figure Test (ROCFT), delayed recall test of a 10‐word list, the Digit Span, the Trail Making Test, the Digit Symbol Substitution Test, and the Letter Word Fluency Test.ResultBetween March 13, 2019, and May 8, 2020, 361 patients were screened and 154 were randomly assigned to the multi‐domain intervention group (n = 81) or control group (n = 73). 110 (71%) participants completed the trial. The full analysis set included 136 patients. In the primary efficacy analysis, there was no significant differences in the change of composite score from baseline to 18‐month follow‐up between the intervention group and the control group (mean difference 0.066 [95% CI ‐0.089 to 0.222]). In the analysis for each neuropsychological test, scores of immediate and delayed recall tests of the ROCFT in the intervention group significantly improved by a mean of 1.627 points and 1.793 points, respectively. The mean difference in the change of score of delayed recall test of the ROCFT between intervention group and control group was significant (mean difference 1.803 [95% CI 0.169 to 3.436]). In subgroup analyses, intervention effect on composite score was significant among patients with moderate to severe white matter hyperintensities (mean difference 0.351 [95% CI 0.088 to 0.614]).ConclusionThe multi‐domain intervention could improve memory function in older adults with type 2 diabetes and MCI.

The association between microbiome and white matter integrity in the elderly with youthful memory in superaging

AbstractBackgroundAging‐related cognitive decline has been regarded as a normal consequence of aging. However, previous research on ‘SuperAgers’ suggests that such decline is not inevitable. The purpose of this study was to investigate the relationship between the microbiome and white matter integrity in SuperAgers, which may help us understand the mechanism that preserves memory function in these individuals.MethodWe enrolled a total of 115 elderly individuals aged 60 years or older with normal cognitive function, which was defined as scoring one standard deviation or more above the population norm on tests of memory, attention, language, visuospatial ability, and frontal function in the Seoul Neuropsychological Screening Battery. SuperAgers were defined based on their delayed recall scores compared to middle‐aged adults (45 years old) in both the Seoul Verbal Learning Test and the Rey‐Osterrieth Complex Figure Test. Diffusion tensor images were analyzed using tract‐based spatial statistics (TBSS). Parameters related to diffusion tensors were calculated at the voxel level to generate fractional anisotropy (FA) images using the DTIFit. FA values, a diffusion tensor parameter reflecting white matter fiber tract integrity, were measured and compared between SuperAgers and typical agers using the FSL randomise program. For microbiome analysis, EZ biocloud was used to perform alpha diversity, taxonomic hierarchy, and taxonomic composition analysis for each subject analysis. Group analysis was also conducted using the taxonomic composition values, and further group analysis was carried out using ACE, Chao1, and Jacknife, which are indicators of species richness. Statistical analyses were conducted using Statistical Package for Social Science 19.ResultCompared to typical agers, superagers showed a higher number of Firmicutes and Actinobacteria, which have been associated with higher cognitive function. However, there was no significant difference between superagers and typical agers. Additionally, an analysis of the association between p_firmicutes, c_mollicutes, o_lactobacilales and f_erysipelotrichaceae with white matter integrity showed no significant association.ConclusionBased on these results, it can be inferred that superagers may have a correlation with microbiome strains that are closely related to cognitive function, as well as white matter in the brain

Cognitive reserve in figural and verbal memory in healthy older adults – preliminary results

AbstractBackgroundCognitive reserve plays an important role in individual trajectories of age‐related memory decline, with education and semantic fluency representing cognitive reserve proxies (CRPs). Higher CR may attenuate well‐known effects of ageing on the brain, such as decreases in grey matter volume (GMV). We hypothesised that the known associations between age‐related GMV and cognition would be (differentially) attenuated by CRPs.MethodWe analysed 3‐Tesla T1‐weighted Multi‐Echo MPRAGE and cognitive data (Verbal Learning and Memory Test (VLMT), Rey Complex Figure Test (RCFT), and Regensburg Verbal Fluency Test (RWT)) from 51 cognitively normal adults (73.2±7.62 years, 31 male) in our new cohort established within the CRC1436 (https://sfb1436.de/). MRI data were pre‐processed and analysed using CAT12. We performed a whole‐brain linear regression to first assess age‐related reductions in GMV (covariates: sex, total intracranial volume (TIV), education), extracting mean betas for significant regions of interest (ROIs). We investigated the relationship between GMV in age‐vulnerable regions and memory using linear regressions in R (covariates: age, sex, TIV), and assessed CRPs as moderators on this relationship. Finally, we tested whether CRPs explained variance in memory performance over and above that of GMV and age. We accounted for multiple testing via Benjamini‐Hochberg‐correction.ResultWhole brain analyses identified bilateral hippocampal GMV as negatively associated with age (Fig.1). Linear regression analyses yielded a significant positive association between bilateral hippocampal GMV and figural memory (Fig.2). However, we observed no significant moderation by CRPs on this relationship. Finally, we observed weak evidence for cognitive reserve when adjusting for GMV and age, with higher variance explained by CRPs (Table 1). Semantic fluency positively predicted a figural memory composite when adjusting for right (p = 0.006) as well as left hippocampal GMV (p = 0.014). Education positively predicted verbal memory when adjusting for right (p&lt;0.001) as well as left hippocampal GMV (p&lt;0.001).ConclusionConsistent with operational definitions, our results provide weak evidence for semantic fluency and for education as CRPs in figural and verbal memory, respectively. However, our findings are preliminary, given the future addition of more participants. Nevertheless, these results provide important first insights into cognitive reserve in this developing cohort.

The Impact of Iron Deficiency Anemia on Cerebrovascular Physiology, Brain Structure, and Cognitive Function in Otherwise Healthy Women

Introduction: Moderate iron deficiency anemia(IDA), defined as a hemoglobin below 11 g/dl, occurs in 1.5% of the United States population and is overrepresented in minority populations. IDA is known to cause permanent structural and function damage in children, but IDA's cognitive and neurovascular phenotype in adults is poorly characterized. We performed brain MRI and cognitive testing in 34 otherwise healthy women with IDA to determine whether oxygen delivery and metabolism are preserved as well as the association of IDA with brain volumes and cognitive function. Methods: We recruited potential blood donors from four hospital-based donor centers, Children's Hospital Los Angeles, University of California Los Angeles, Cedar's Sinai, and City of Hope, whose point-of-care hemoglobin values were less than 10.5 g/dl. We also recruited individuals from the community using social media advertisements, with anemia documented by screening hemoglobin assessment. All participants were free from inflammatory, infectious, or malignant diseases that may impact blood counts and iron metabolism. IDA was confirmed by laboratory assessment of CBC, reticulocyte count, iron indices, methyl malonic acid, hemoglobin electrophoresis, homocysteine, and high-sensitivity C-reactive protein. Patients underwent a four-hour neurocognitive assessment consisting of subsets from the Weschler Abbreviated Scale of Intelligence (WASI-II), the California Verbal Learning Test (CVLT), the Rey Complex Figure Test (RCFT), and the NIH Cognitive Toolkit. MRI was performed on a 3T Philips Achieva using a 32-element head coil. Anatomic imaging consisted of 3D T1, 3D T2, 3D T2*/QSM, and 2D multishell diffusion imaging. Phase contrast and arterial spin labeling measured total and regional brain blood flow, respectively. Cerebral venous oximetry was performed using T2 relaxation under spin tagging. Results: The study population demonstrated a classic IDA phenotype characterized by low ferritin and transferrin saturation, high iron binding capacity, decreased MCV and MCHC, and hypochromic microcytosis on blood smear (not shown). Neurocognitive function was impaired across multiple domains for women having hemoglobin values less than 10.0 g/dl (Figure 1, left), with Cohen's D values ranging from 0.7 - 1.5. Cerebral blood flow (CBF) rose slightly as oxygen content declined (Figure 1, right), but much less than predicted based on historical controls 1,2 leading to impaired brain oxygen delivery. Oxygen extraction fraction was independent of hemoglobin concentration, thus cerebral metabolic rate was also decreased. Grey matter volume was smaller in the right temporal lobe and correlated with 2/3 of the abnormal cognitive indices (in Figure 1, left). White matter volume was decreased in the right cingulate gyrus, corpus callosum, and cerebellum, correlating with the remaining abnormal cognitive indices. Discussion: Our study demonstrates that iron deficiency has serious effects on cognitive performance; individuals with hemoglobin less than 10.0 g/dl scored more than one standard deviation below their peers with milder anemia. Poor cognitive performance was correlated with demonstrable brain shrinkage whose reversibility is unknown. The failure of the brain to upregulate CBF in response to IDA was striking because most patients with chronic anemia preserve cerebral oxygen delivery through compensatory hyperemia 1,2. While both anemia and iron deficiency can impair brain function on their own, it is likely that iron deficiency is the primary contributor to the cognitive and neurovascular effects. We will test this hypothesis in subsequent work by reexamining women with IDA shortly after intravenous iron administration, thus creating a window where the iron deficiency has been corrected but the anemia persists(NCT05929729). We will also determine whether the cerebrovascular, anatomic, and functional deficits are reversible with iron repletion.

Benefits of vagus nerve stimulation on psychomotor functions in patients with severe drug-resistant epilepsy

PurposePatients with severe drug-resistant epilepsy (DRE) experience psychomotor disorders. Our study aimed to assess the psychomotor outcomes after vagus nerve stimulation (VNS) in this population. MethodsWe prospectively evaluated psychomotor function in 17 adult patients with severe DRE who were referred for VNS. Psychomotor functions were examined, in the preoperative period and at 18 months post-surgery, by a psychomotor therapist using a full set of the following specific tests: the Rey–Osterrieth complex figure (ROCF) test, the Zazzo's cancelation task (ZCT), the Piaget-Head test and the paired images test. ResultsAt 18 months post-VNS surgery, the Piaget-head scores increased by 3 points (p = 0.008) compared to baseline. Performances were also improved for ROCF test both in copy (+2.4 points, p = 0.001) and recall (+2.0 points, p = 0.008) tasks and for the paired images test (accuracy index: +28.6 %, p = 0.03). Regarding the ZCT findings, the efficiency index increased in both single (+16 %, p = 0.005) and dual (+17.1 %, p < 0.001) tasks. QoL improved in 88.2 % of patients. ConclusionsPatients with severe DRE treated with VNS experienced improved performance in terms of global psychomotor functions. Perceptual organization, visuospatial memory, laterality awareness, sustained attention, concentration, visual scanning, and inhibition were significantly improved.

Long-term effects of vagus nerve stimulation therapy on cognitive functioning in patients with drug-resistant epilepsy.

Despite the increasing use of vagus nerve stimulation (VNS) for drug-resistant epilepsy, its impact on cognitive functioning remains insufficiently investigated. We aimed to comprehensively assess changes in cognition after long-term VNS therapy in a prospective sample of adults with epilepsy. Between December 2019 and March 2023, patients scheduled for VNS implantation were invited for neuropsychological assessment, including tests of executive functions, working and short-term memory (recall of a verbal logical story and the Rey-Osterrieth complex figure (ROCF)), and social cognition. Participants were re-evaluated after a year of VNS therapy and the pre- and postoperative scores were compared by means of the Student's t or Wilcoxon's signed rank tests for paired samples. Patients available only after a longer follow-up (more than 24 months) were also re-examined and included in a secondary analysis. The study included 28 PWE (16, 57.1% female, average age 33.7 ± 10.0 years). Twenty-two PWE followed-up at 14.5 ± 4.8 months had worse categorical verbal fluency than preoperatively (t = 2.613, p = 0.016). After including patients with long follow-up (n = 28, 21.6 ± 11.4 months), the group scored better on the delayed recall of the ROCF (17.09 ± 8.84 to 20.65 ± 8.32 points, t(22) = - 2.618, p = 0.016) and the Happé strange stories test (5.0 ± 2.6 to 6.1 ± 2.1 points, t(14) = - 3.281, p = 0.005). No significant changes were observed in other cognitive domains (p > 0.05). We suggest improvements in a task of social cognition and short-term visual memory after longer use of VNS therapy. Such findings should be confirmed in larger trials after controlling for changes in ictal or interictal activity.

A Process Analysis of Rey-Osterrieth Complex Figure Test Performance Using the Boston Qualitative Scoring System in HIV-Associated Neurocognitive Disorders.

Deficits in episodic verbal memory are commonly observed in persons with HIV (PWH) disease, in whom they are characterized by dysregulation of the executive aspects of encoding and retrieval and adversely impact everyday functioning. Deficits in episodic visual memory are also apparent in PWH, but we know less about their cognitive architecture. This study used the Boston Qualitative Scoring System (BQSS) for the Rey-Osterrieth Complex Figure (ROCF) to examine visual learning and recall in 43 individuals without HIV and 141 PWH who completed a full research neuropsychological, psychiatric, and medical assessment. A mixed model covarying for education and estimated verbal IQ showed that participants with HIV-associated neurocognitive disorders (HAND) performed worse than PWH without neurocognitive disorders and HIV- participants at comparable medium-to-large effect sizes across the Copy, Immediate, and Delayed trials of the BQSS-ROCF, suggesting a primary encoding deficit. A component process analysis of the BQSS-ROCF Copy Trial revealed that participants with HAND had specific difficulties with configural accuracy, cluster accuracy, and cluster placement. Within the PWH sample, measures of motor coordination and executive functions emerged as independent predictors of BQSS-ROCF Copy Trial performance. Findings extend prior research by showing that HAND may be associated with a primary encoding deficit for complex visuomotor learning and memory tasks that is driven by a combination of visuospatial, motor, and executive difficulties.

3 Rey Complex Figure Scoring Made Simple: Data from the Emory Healthy Brain Study

Objective:The Rey Complex Figure (CF) is a popular test to assess visuospatial construction and visual memory, but its broader use in clinical research is limited by scoring complexity. To widen its application, we developed a new CF scoring system similar to the Benson Figure in which 10 primary CF elements are scored according to presence and location. A novel recognition task was also created for each of these 10 items consisting of a 4-choice recognition condition containing the primary rectangle and major interior lines with qualitative variations of target elements as distractors. The current investigation was designed to characterize the relationship between scoring methods and establish whether comparable results are obtained across both traditional and new CF scoring approaches.Participants and Methods:Participants from the Emory Health Brain Study (EHBS) who had completed the Rey CF copy during their cognitive study visit were studied. All participants were self-identified as normal, and administered the CF according to our previously published procedure that included the Copy, Immediate Recall (∼ 30 seconds), and 30-minute Delayed Recall (Loring et al., 1990). Following delayed recall, CF recognition was assessed using the Meyers and Myers (1995) recognition followed by the newly developed forced choice recognition. The final sample included 155 participants ranging in age from 51.6 years to 80.0 years (M=64.9, SD=6.6). The average MoCA score was 26.8/30 (SD=6.6).Results:Mean performance levels across conditions and scoring approaches are included in the table. Correlations between Copy, Immediate Recall, Delayed Recall, and Recognition were calculated to evaluate the relationship between the traditional 18 item/36 point Osterrieth criteria and newly developed CF scoring criteria using both parametric and non-parametric approaches. Pearson correlations demonstrated high agreement between approaches when characterizing performance levels across all CF conditions (Copy r=.72, Immediate Recall r=.87, Delayed Recall r=.90, and Recognition r=.52). Similar correlations were present using non-parametric analyses (Copy ρ=.46, Immediate Recall ρ=.83, Delayed Recall ρ=.91, and Recognition ρ=.42). Table. Mean performance levels across conditions and scoring approachesConclusions:The high correlations, particularly for Immediate and Delayed Recall conditions, suggest that the modified simpler scoring system is comparable to the traditional approach, thereby suggesting potential equivalence between scoring methods. When comparing Rey’s original 47 point scoring approach to his 36 point scoring system, Osterrieth (1944) reported a correlation in fifty adults of ρ=.95 and a correlation in twenty 6-year-olds of ρ=.92. In this investigation, lower correlations were observed for copy and recognition conditions, in part representing smaller response distribution across participants. Although these preliminary results are encouraging, to implement the new EHBS scoring method in clinical evaluation, we are developing normative data in participants across the entire EHBS series, many of whom were not administered the new CF Recognition. We are also examining performances in patients undergoing DBS evaluation for Parkinson Disease to explore its clinical sensitivity. Simpler scoring will permit greater CF clinical and research application.

37 Perceived Financial Exploitation Vulnerability is Associated with Morphometry of the Parahippocampal Gyrus and Entorhinal Cortex in Cognitively Normal Older Adults

Objective:Prior work suggests financial exploitation vulnerability may be an early behavioral manifestation of Alzheimer’s disease (AD). Brain morphometric measures of the parahippocampal gyrus and entorhinal cortex have been shown to be sensitive to early AD progression. We hypothesized that perceived financial exploitation vulnerability may be associated with morphometric measures of the parahippocampal gyrus and entorhinal cortex in cognitively unimpaired older adults. We secondarily investigated the association of morphometric measures with neuropsychological measures.Participants and Methods:The sample consisted of 39 cognitively unimpaired older adults (mean age = 68.74 ± 6.43, mean education = 16.87 ± 2.35, 77% female). Cognitive impairment was screened using the telephone version of the Montreal Cognitive Assessment (MoCA) and the cut-off was 21 for study participation. Perceived financial exploitation vulnerability was characterized using a 6-item self-report measure derived from the contextual items of the Lichtenberg Financial Rating Scale. Neuropsychological measures included the CVLT-II Long Delay Free Recall (verbal memory), Benson Complex Figure Recall (visual memory), and Verbal Fluency: Phonemic Test from the Alzheimer’s Disease Centers’ Uniform Data Set (UDS) version 3. Brain images were collected on a 7 Tesla Siemens Magnetom with the following parameters: TE=2.95ms, TR=2200ms, 240 sagittal slices, acquired voxel size (avs)=0.7mm x 0.7mm x 0.7mm. Structural brain images were processed using FreeSurfer version 7.2.0. Cortical thickness and volume measures were generated using the Killiany/Desikian parcellation atlas. Regions were averaged across hemispheres to obtain a single value for each region. Volume measures were adjusted for intracranial volume. Bivariate analyses were conducted to assess relationships between each outcome variable and potential confounders (age, sex, and education). Linear regression models were adjusted for any covariates significantly associated with the outcome variable (none for perceived financial exploitation vulnerability; sex and age for verbal memory; education for visual memory; sex for verbal fluency).Results:Smaller entorhinal cortex volume (β = -1275.14, SE = 582.79, p &lt; 0.05) and lower parahippocampal gyrus thickness (β = -3.37, SE = 1.57, p &lt; 0.05) were significantly associated with greater perceived financial exploitation vulnerability. Lower entorhinal cortex thickness was marginally associated with greater perceived financial exploitation vulnerability (β = -2.03, SE = 1.11, p = 0.08). Higher parahippocampal gyrus thickness was associated with better verbal fluency (β = 17.66, SE = 7.01, p &lt; 0.05). Higher entorhinal cortex thickness was associated with better visual memory (β = 4.71, SE = 1.73, p &lt; 0.05). No significant associations were observed between structural brain measures and verbal memory.Conclusions:These results suggest smaller entorhinal cortex volume and lower parahippocampal gyrus thickness are associated with higher perceived financial exploitation vulnerability in cognitively normal older adults. Additionally, parahippocampal gyrus thickness appears to be associated with verbal fluency abilities while entorhinal cortex thickness appears to be associated with visual memory. Taken together, these findings lend support to the notion that financial exploitation vulnerability may serve as an early behavioral manifestation of preclinical AD. Longitudinal studies are needed to better understand the temporal nature of these relationships.

17 Observing Constructs of Drawing Process of the Rey-Osterrieth Complex Figure Test as an Indicator of Persisting Post-Concussive Symptoms

Objective:Evidence regarding cognitive impairment following concussion/mild traumatic brain injury (mTBI) has been conflicting. Criticism has focused on what is being measured, how it is being measured, and who is being measured (Pertab et al, 2009; Iverson, 2010). However, literature suggests that clinicians and researchers should examine how individuals complete a task rather than what they achieve (Geary et al, 2011). Studies examining the drawing process used to complete the Rey-Osterrieth Complex Figure Task (RCF) have been inconclusive and methodologically weak. The current study addressed several criticisms and limitations by examining whether observing RCF drawing process, including a novel strategy construct, could support a diagnosis of persisting post-concussive symptoms.Participants and Methods:Sixteen individuals with a history of concussion/mTBI and sixteen matched controls (age, sex, IQ) were included in multiple regression analyses to examine whether RCF drawing constructs predict post-concussive symptoms (mean age 43.59 years; 22 female). At least 3 months had passed since the concussive/mTBI event. Post-concussive symptoms were assessed with the Rivermead Post-Concussive Symptoms Questionnaire (RPCSQ) and the Mental Fatigue Scale (MFS). Separate regression analyses were conducted for each scale. Predictor variables were statistically selected from a catalogue of 4 RCF drawing process constructs - Wholeness, Order, Continuation and Strategy; 15 traditional measures of cognitive function; and 3 psychological state measures. 17 variables were included in the model for the RPCSQ, including Order and Strategy. 18 variables were included for the MFS, including Order, Continuation and Strategy.Results:Order scores were found to be one of the strongest predictors of RPCSQ scores (B = -2.06; ß= 0.20), and MFS scores (B = -1.54, ß = 0.26). Individuals drawing fewer core elements at the start of the drawing process were found to report more post-concussive symptoms. Participants who observed a stronger temporal-spatial strategy heuristic, as measured by the Strategy construct, reported more symptoms, particularly mental fatigue (RPCSQ: B = 0.49, ß = 0.09; MFS: B = 0.58, ß = 0.19). Continuation was also found to be predictive of MFS scores (B = -0.24, ß = -0.14), such that the fewer continuation points that were observed, the greater the MFS score.Conclusions:Two constructs of RCF drawing process - Order and Strategy - were found to predict persisting post-concussive symptoms generally, and mental fatigue specifically. Continuation was also found to predict mental fatigue. Such findings provide a cognitive explanation for patient reports of mental fatigue following concussion - recognised as the most common and persistent symptom. Strict adherence to a temporal-spatial strategy may indicate cognitive inflexibility - a theory supported by the inclusion and influence of other cognitive tasks in the regression models that rely on cognitive flexibility. Individuals exert more effort to shift between perceptual planes and to override global bias, thereby expending cognitive resources more quickly and to a greater extent. These findings provide a credible explanation for the lack of evidence of cognitive impairments in previous research, where neuropsychological tasks focus on attainment rather than process. These findings highlight the clinical importance of assessing cognitive dysregulation, specific cognitive processes and cognitive deficits post-concussion/mTBI.

1 Associations Between Alcohol-Related Problems, Neuropsychological Measures, and Financial Exploitation Vulnerability in a Low-Drinking Sample of Cognitively Unimpaired Older Adults

Objective:In recent years, rates of alcohol consumption and alcohol use disorder have steadily increased among adults age 60 and older. Large studies have demonstrated that moderate-to-heavy alcohol consumption (&gt;7 drinks per week) is a risk factor for developing various types of dementias. The effects of alcohol-related problems on cognition are less clear, and are particularly understudied in older adults. Similarly, while there is an established link between worse cognition and financial exploitation vulnerability in older adults, no studies have examined relationships between alcohol-related problems and financial exploitation in this population. The current study therefore explores whether alcohol-related problems are associated with neuropsychological performance and financial exploitation vulnerability in a sample of older adults.Participants and Methods:Participants were a community sample of cognitively unimpaired adults over the age of 50 (N = 55, Age M(SD) = 69.1(6.2), 74.5% female, Years of education M(SD) = 16.8(2.3)). Interested individuals were excluded if they reported current or past substance use disorders. Participants completed a laboratory visit that included a neuropsychological assessment. Measures included the NIH Cognition toolbox, CVLT-II, Digit Span, Trails A/B, Benson Complex Figure Recall, and Verbal Fluency: Phonemic and Semantic, from the Alzheimer’s Disease Centers’ Uniform Data Set (UDS) version 3. Participants completed the CAGE Alcohol Abuse Screening Tool and the Short Michigan Alcohol Screener Test - Geriatric Version (SMAST) to assess alcohol-related problems. Both measures are used as clinical screening tools to measure likelihood of a substance use disorder and produce a summary score (0-4 for CAGE, 010 for SMAST) tabulating symptoms of alcohol-related problems. Participants also completed the Perceived Financial Vulnerability Scale (PFVS) to assess financial exploitation vulnerability. As a significant number of participants reported no drinking and therefore no alcohol-related problems, negative binomial regressions were used to test associations between neuropsychological measures, financial exploitation vulnerability, and alcohol-related problems.Results:After covarying for age and sex, SMAST was negatively associated with NIH toolbox total cognition (B(SE) = -.14(.07), p&lt;.05) and marginally negatively associated with fluid cognition (B(SE) = -.07(.04), p=.06). Neither SMAST nor CAGE scores were significantly associated with performance on any other neuropsychological test (ps = .13-.99). SMAST was positively associated with financial exploitation vulnerability (B(SE) = .31(.16), p = .05); this effect remained significant after covarying for NIH total composite score in a secondary analysis.Conclusions:In a community sample of cognitively unimpaired, low-drinking adults over the age of 50, more alcohol-related problems were associated with worse NIH toolbox cognition scores. Similarly, more alcohol-related problems were associated with greater financial exploitation vulnerability, and this relationship was not driven by worse cognition. These results suggest that even low amounts of drinking and alcohol-related problems may be associated with cognition and financial exploitation vulnerability in cognitively unimpaired older adults. This study also corroborates the use of the SMAST over the CAGE in older adult populations that may be more sensitive to cognitive changes.

38 Real-World Goal Setting and Follow Through in Young and Older Adults

Objective:The ability to generate, plan for, and follow through with goals is essential to everyday functioning. Compared to young adults, cognitively normal older adults have more difficulty on a variety of cognitive functions that contribute to goal setting and follow through. However, how these age-related cognitive differences impact real-world goal planning and success remains unclear. In the current study, we aimed to better understand the impact of older age on everyday goal planning and success.Participants and Methods:Cognitively normal young adults (18-35 years, n= 57) and older adults (60-80 years, n= 49) participated in a 10-day 2-session study. In the first session, participants described 4 real-world goals that they hoped to pursue in the next 10 days. These goals were subjectively rated for personal significance, significance to others, and vividness, and goal descriptions were objectively scored for temporal, spatial, and event specificity, among other measures. Ten days later, participants rated the degree to which they planned for and made progress in their real-world goals since session one. Older adults also completed a battery of neuropsychological tests.Results:Some key results are as follows. Relative to the young adults, cognitively normal older adults described real-world goals which navigated smaller spaces (p=0.01) and that they perceived as more important to other people (p=0.03). Older adults also planned more during the 10-day window (p&lt;0.001). There was not a statistically significant age group difference, however, in real-world goal progress (p=0.65). Nonetheless, among older participants, goal progress was related to higher mental processing speed as shown by the Trail Making Test Part A (r=0.36, p=0.02) and the creation of goals confined to specific temporal periods (r=0.35, p=0.01). Older participants who scored lower on the Rey Complex Figure Test (RCFT) long delay recall trial reported that their goals were more like ones that they had set in the past (r= -0.34, p=0.02), and higher episodic memory as shown by the RCFT was associated with more spatially specific goals (r=0.32, p=0.02), as well as a greater use of implementation intentions in goal descriptions(r=0.35, p=0.02).Conclusions:Although older adults tend to show decline in several cognitive domains relevant to goal setting, we found that cognitively normal older adults did not make significantly less progress toward a series of real-world goals over a 10-day window. However, relative to young adults, older adults tended to pursue goals which were more important to others, as well as goals that involved navigating smaller spaces. Older adults also appear to rely on planning more than young adults to make progress toward their goals. These findings reveal age group differences in the quality of goals and individual differences in goal success among older adults. They are also in line with prior research suggesting that cognitive aging effects may be more subtle in real-world contexts.