Anticholinergic Drug Burden and Neurocognitive Performance in the Study of Latinos-Investigation of Neurocognitive Aging

Background: Studies of cumulative anticholinergic drug burden on cognitive function and impairment are emerging, yet few for Hispanics/Latinos. Objective: To examine associations between anticholinergic use and neurocognitive performance outcomes among diverse Hispanics/Latinos. Methods: This prospective cohort study included diverse Hispanic/Latino participants, enrolled in the Study of Latinos-Investigation of Neurocognitive, from New York, Chicago, Miami, and San Diego (n = 6,249). Survey linear regression examined associations between anticholinergic use (measured during baseline [Visit 1] and average 7-year follow up [Visit 2]) with global cognition, episodic learning, memory, phonemic fluency, processing speed, executive functioning, and average 7-year change. Results: Anticholinergic use was associated with lower cognitive global cognition (β= –0.21; 95% CI [–0.36; –0.05]), learning (β= –0.27; 95% CI [–0.47; –0.07]), memory (β= –0.22; 95% CI [–0.41; –0.03]), and executive functioning (β= –0.22; 95% CI [–0.40; –0.03]) scores, particularly among those who took anticholinergics at both visits. Anticholinergic use was associated with faster decline in global cognition, learning, and verbal fluency (β: –0.28 [95% CI: –0.55, –0.01]; β: –0.28 [95% CI: –0.55, –0.01]; β: –0.25, [95% CI –0.47, –0.04], respectively). Sex modified associations between anticholinergic use with global cognition, learning, and executive functioning (F 3 = 3.59, F 3 = 2.84, F 3 = 3.88, respectively). Conclusion: Anticholinergic use was associated with lower neurocognitive performance, especially among those who used anticholinergics at both visits, among a study population of diverse Hispanics/Latinos. Findings will support evidence-based decisions regarding anticholinergic prescriptions and efforts to minimize cognitive impact.

COVID-19 and Cognitive Impairment: A Cross-Sectional Clinic Based Study

Background: Patients with dementia are more prone to acquire COVID-19 infection. Patients with COVID-19 showed a tendency to develop cognitive impairment. Objectives: We aimed to study the clinical manifestations of COVID-19 infection among adult Sudanese demented patients and the prevalence of cognitive impairment among adult Sudanese non demented patients. Methodology: This is a descriptive cross-sectional study which took place in Sudan, Khartoum state in the period (September-December 2021) in a private neurology/psychiatry clinic. 135 adult Sudanese patients were included in this study and were divided into two groups. The first group consists of 100 patients with a known history of dementia that got infected recently with COVID-19, while the second group consists of 35 patients who developed some sort of cognitive impairment after recovering from COVID-19 infection. Regarding the second group, cognitive functions were assessed by senior consultant neurologist and senior consultant psychiatrist using a well validated neuropsychological measure. Results: Out of 100 patients in the first group, females were 60 and males were 40. Age distribution is between 63 -98. The common presenting symptoms of COVID-19 among this group were: Cough and fever (90 patients), diarrhea and vomiting (5 patients), breathlessness (4 patients), coughing of blood (5 patients), convulsions (1 patient), paraplegia (1 patient) and hemiplegia (1 patient). Regarding the second group, Age distribution varied from 30 to 80 years. Cognitive functions impairment was noticed as follows: Memory recall (22%), memory recognition (23%), memory encoding (24%), processing speed (16%), executive functioning (19%), phonemic fluency (17%) and category fluency (17%). Conclusion: Patients with dementia are more susceptible to develop COVID-19 infection. Patients with COVID-19 Infection are at risk of developing some sort of cognitive impairment after recovery.

10-Hz tACS Over The Prefrontal Cortex Improves Phonemic Fluency

Verbal fluency is an important indicator of human verbal ability. Methods to improve fluency is an interesting issue necessitating investigation. To do this, the current study required participants to randomly receive transcranial alternating current stimulation (tACS) at 10 Hz, 40 Hz (control frequency), and sham stimulation over the prefrontal cortex before a phonemic fluency task. It was found that 10-Hz tACS significantly improved phonemic fluency relative to sham stimulation. This result demonstrates the modulatory effect of 10-Hz tACS on language ability.

Multi-model mapping of phonemic fluency

The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analyses approaches. We investigated a large number of patients with focal unilateral right or left frontal (n = 110) or posterior (n = 100) or subcortical (n = 65) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcel-based lesion symptom mapping, tract-wise statistical analysis as well as Bayesian multivariate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcel-based lesion symptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multivariate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localised left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of energization, which sustains activation for the duration of the task and middle and inferior frontal regions concerned with selection, required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes.

Are There Any Cognitive and Behavioral Changes Potentially Related to Quarantine due to the COVID-19 Pandemic in People with Mild Cognitive Impairment and AD Dementia? A Longitudinal Study

The aim of the study was to examine potential cognitive, mood (depression and anxiety) and behavioral changes that may be related to the quarantine and the lockdown applied during the COVID-19 pandemic in Greek older adults with mild cognitive impairment (MCI), and AD dementia in mild and moderate stages. Method: 407 older adults, diagnosed either with MCI or AD dementia (ADD), were recruited from the Day Centers of the Greek Association of Alzheimer Disease and Related Disorders (GAADRD). Neuropsychological assessment was performed at baseline (at the time of diagnosis) between May and July of 2018, as well as for two consecutive follow-up assessments, identical in period, in 2019 and 2020. The majority of participants had participated in non-pharmacological interventions during 2018 as well as 2019, whereas all of them continued their participation online in 2020. Results: Mixed measures analysis of variance showed that participants’ ‘deterioration difference—D’ by means of their performance difference in neuropsychological assessments between 2018–2019 (D1) and 2019–2020 (D2) did not change, except for the FUCAS, RAVLT, and phonemic fluency tests, since both groups resulted in a larger deterioration difference (D2) in these tests. Additionally, three path models examining the direct relationships between performance in tests measuring mood, as well as everyday functioning and cognitive measures, showed that participants’ worsened performance in the 2019 and 2020 assessments was strongly affected by NPI performance, in sharp contrast to the 2018 assessment. Discussion: During the lockdown period, MCI and ADD patients’ neuropsychological performance did not change, except from the tests measuring verbal memory, learning, and phonemic fluency, as well as everyday functioning. However, the natural progression of the MCI as well as ADD condition is the main reason for participants’ deterioration. Mood performance became increasingly closely related to cognition and everyday functioning. Hence, the role of quarantine and AD progression are discussed as potential factors associated with impairments.

Functional Connectivity and Compensation of Phonemic Fluency in Aging

Neural compensatory mechanisms associated with broad cognitive abilities have been studied. However, those associated with specific cognitive subdomains (e.g., verbal fluency) remain to be investigated in healthy aging. Here, we delineate: (a) neural substrates of verbal (phonemic) fluency, and (b) compensatory mechanisms mediating the association between these neural substrates and phonemic fluency. We analyzed resting-state functional magnetic resonance imaging from 133 right-handed, cognitively normal individuals who underwent the Controlled Oral Word Association Test (COWAT) to record their phonemic fluency. We evaluated functional connectivity in an established and extended language network comprising Wernicke, Broca, thalamic and anti-correlated modules. (a) We conducted voxel-wise multiple linear regression to identify the brain areas associated with phonemic fluency. (b) We used mediation effects of cognitive reserve, measured by the Wechsler Adult Intelligence Scale—Information subtest, upon the association between functional connectivity and phonemic fluency tested to investigate compensation. We found that: (a) Greater functional connectivity between the Wernicke module and brain areas within the anti-correlated module was associated with better performance in phonemic fluency, (b) Cognitive reserve was an unlikely mediator in younger adults. In contrast, cognitive reserve was a partial mediator of the association between functional connectivity and phonemic fluency in older adults, likely representing compensation to counter the effect of aging. We conclude that in healthy aging, higher performance in phonemic fluency at older ages could be attributed to greater functional connectivity partially facilitated by higher cognitive reserve, presumably reflecting compensatory mechanisms to minimize the effect of aging.

159 The Role of Education on the Association between OSA and Cognitive Functions in Middle-age and Older Adults

Introduction A weak relation between an increase in education and improved health knowledge was observed among those who attended college, but not among those whose highest educational level attainment was high school (Altindag, Cannonier, & Mocan, 2014). Alachantis and colleagues (2005) had applied cognitive reserve theory (Stern, 2002) to help explain why OSA patients with higher intelligence scores perform well on cognitive tasks. The resource substitution theory (RST; Ross & Mirowsky, 2006) posits that higher education compensates for background disadvantages rather than magnifying background advantages. The goals of the current study were to examine the interaction between educational level and obstructive sleep apnea (OSA) on cognitive functions such as verbal fluency, psychomotor vigilance, executive functions, visuospatial ability, and attention span and to determine whether the results would support the RST. Methods One hundred and nine participants (47 ApneaLinkTM -screened controls and 62 untreated OSA patients) participated in the study and completed the Wisconsin Card Sorting Test, WAIS-III digit span and block design, semantic and phonemic fluency tests, and a psychomotor vigilance task. Subjective sleep (PSQI and ESS) and health measures (depression, anxiety, mood disturbance, diabetes, hypertension) were assessed. A hierarchical regression was conducted to test for the additional variance explained by the interaction term even after accounting for the covariates. Results In semantic fluency and visuospatial ability tasks, patients with higher education performed better than patients with high school or less education. This moderation effect of education was not observed for the control group. A significant interaction effect was not observed for vigilance, phonemic fluency, attention span, or executive functions although education was a significant predictor for all cognitive tasks. Conclusion The resource substitution theory was supported as the benefit of education seemed more crucial for OSA patients than for controls, specifically in semantic fluency and visuospatial ability. This benefit of higher education contributing to larger cognitive reserves in patients with OSA helped buffer some cognitive deficits but not for others, but this buffer no longer works when the cognitive demand gets larger. Support (if any) A grant from the Center for Integrative Research on Cognitive Neural Science, Southern Illinois University Carbondale was received.

Cortical Networks Underpinning Compensation of Verbal Fluency in Normal Aging

Elucidating compensatory mechanisms underpinning phonemic fluency (PF) may help to minimize its decline due to normal aging or neurodegenerative diseases. We investigated cortical brain networks potentially underpinning compensation of age-related differences in PF. Using graph theory, we constructed networks from measures of thickness for PF, semantic, and executive–visuospatial cortical networks. A total of 267 cognitively healthy individuals were divided into younger age (YA, 38–58 years) and older age (OA, 59–79 years) groups with low performance (LP) and high performance (HP) in PF: YA-LP, YA-HP, OA-LP, OA-HP. We found that the same pattern of reduced efficiency and increased transitivity was associated with both HP (compensation) and OA (aberrant network organization) in the PF and semantic cortical networks. When compared with the OA-LP group, the higher PF performance in the OA-HP group was associated with more segregated PF and semantic cortical networks, greater participation of frontal nodes, and stronger correlations within the PF cortical network. We conclude that more segregated cortical networks with strong involvement of frontal nodes seemed to allow older adults to maintain their high PF performance. Nodal analyses and measures of strength were helpful to disentangle compensation from the aberrant network organization associated with OA.

Equivalence of Traditional and Internet-Delivered Testing of Word Fluency Tasks

Changes from traditional face-to-face to internet-delivered psychological assessment are urgently needed giventhe long-lasting pandemic, the general need for fast and efficient tests and test procedures, and easier availabilityand access for test-takers in remote settings. We used a quasi-experimental non-randomized group design for thecomparison of two word fluency test procedures: one traditional that is face-to-face (n = 30) and one supervisedvia internet (n = 30). Participants were 17-31 years, education level high school and Bachelor. The letters S, K, Twere used for the phonemic fluency test, for the emotion word fluency test subjects had to generate words relatedto subjective emotional feelings or the expression of emotions. The results showed that traditional administeredand internet-delivered testing are equivalent (our hypothesis) as seen from the absence of significant differencesbetween the two groups in the performances of all four word fluency tests (p > .05) and small effect sizes (Cohen’sd range < .5). Significant correlations were found between the fluency tasks, irrespective of the way of testadministration (p < .05). It can be concluded that the word fluency tasks can be assessed by supervised internet-delivered testing, but this is limited to a sample of young adults.