Search

Objective: High-definition transcranial direct current stimulation (HD-tDCS) has the potential to improve cognitive functioning following neurological injury and in neurodegenerative conditions. In this case report, we present the first use of HD-tDCS in a person with severe anterograde amnesia following carbon monoxide poisoning., Method: The participant underwent two rounds of HD-tDCS that were separated by 3 months (Round 1 = 30 sessions; Round 2 = 31 sessions). We used finite element modeling of the participant's structural MRI to develop an individualized montage that targeted multiple brain regions involved in memory encoding, as identified by Neurosynth., Results: Overall, the participant's objective cognitive functioning improved significantly following Round 1, declined during the 2 months without HD-tDCS, and again improved following Round 2. Subjective informant reports from family and medical personnel followed this same pattern of improvement following each round with a decline in between rounds. We also provide preliminary evidence of altered brain activity during a learning/memory task using functional near-infrared spectroscopy, which may help establish the physiological effects of HD-tDCS in future work., Conclusion: Overall, these findings reinforce the potential value of HD-tDCS as a user-friendly method of enhancing cognition following anoxic/hypoxic brain injury.

Logopenic variant primary progressive aphasia (lvPPA) is characterized by word-finding deficits and phonologic errors in fluent speech. Transcranial direct current stimulation (tDCS) targeting either left temporoparietal junction (TPJ) or left inferior frontal gyrus (IFG) show evidence of improving language function in lvPPA. The present case study evaluated the effects of two separate rounds of high definition tDCS (HD-tDCS) (4 mA; 30 sessions) on language and functional neuroimaging in a 57-year-old woman with lvPPA. Stimulation was centred on two different regions across rounds: (1) left TPJ, and (2) left (IFG). Results showed an improved proportion of content to floorholder words during a naturalistic speech task through both rounds as well as change in confrontation naming after TPJ (improvement) and IFG (worsened) stimulation. fMRI connectivity during task showed left lateralized positive correlations following round 1 and anti-correlations with components of the default mode network following round 2. Resting state segregation of a language-associated functional network increased following both rounds, and task-based segregation of the same network increased following IFG stimulation. These results suggest that stimulation to both regions using HD-tDCS may improve language function in lvPPA, while simultaneously eliciting widespread changes beyond the targeted area in neuronal activity and functional connectivity.

Transcranial alternating current stimulation (tACS) is a form of noninvasive brain stimulation that has experienced rapid growth within the aging population over the past decade due to its potential for modulating cognitive functioning across the "intact" to dementia spectrum. For this reason, we performed a systematic review of the literature to evaluate the efficacy of tACS on cognitive functioning in older adults, including those with cognitive impairment. Our review was completed in June 2023 using Psych INFO, Embase, PubMed, and Cochrane databases. Out of 479 screened articles, 21 met inclusion criteria and were organized according to clinical diagnoses. Seven out of nine studies targeted cognitively intact older adults and showed some type of cognitive improvement after stimulation, whereas nine out of twelve studies targeted clinical diagnoses and showed improved cognitive performance to varying degrees. Studies showed considerable heterogeneity in methodology, stimulation parameters, participant characteristics, choice of cognitive task, and analytic strategy, all of which reinforce the need for standardized reporting of tACS methods. Through this heterogeneity, multiple patterns are described, such as disease progression influencing tACS effects and the need for individualized tailoring. For clinical translation, it is imperative that the field (a) better understand the physiological effects of tACS in these populations, especially in respect to biomarkers, (b) document a causal relationship between tACS delivery and neurophysiological/cognitive effects, and (c) systematically establish dosing parameters (e.g., amplitude, stimulation frequency, number and duration of sessions, need for booster/maintenance sessions)., Competing Interests: Declarations. Ethical Approval: Not applicable. Competing Interests: BMH is an Associate Editor for Neuropsychology Review. No other interests (e.g., funding, employment, financial, non-financial) are present., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the joint contributions of Alzheimer's disease (AD) pathology and brain function to MBI remain unclear., Methods: We test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks, using data from 128 participants with diagnosis of amnestic mild cognitive impairment or mild dementia-AD type., Results: We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI., Discussion: Our findings suggest that tau pathology contributes to MBI primarily by disrupting salience network function and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations., Highlights: Network segregation mediates Alzheimer's disease (AD) pathology impact on mild behavioral impairment (MBI). The salience network is pivotal in linking tau pathology and MBI. This study used path analysis with AD biomarkers and network integrity. The study evaluated the roles of salience, default mode, and frontoparietal networks. This is the first study to integrate MBI with AD biomarkers and network functionality., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: Repeated spaced sessions of repetitive transcranial magnetic stimulation (TMS) to the human primary motor cortex can lead to dose-dependent increases in motor cortical excitability. However, this has yet to be demonstrated in a defined cortical circuit. We aimed to examine the effects of repeated spaced cortical paired associative stimulation (cPAS) on excitability in the motor cortex., Methods: cPAS was delivered to the primary motor cortex (M1) and posterior parietal cortex (PPC) with two coils. In the multi-dose condition, three sessions of cPAS were delivered 50-min apart. The single-dose condition had one session of cPAS, followed by two sessions of a control cPAS protocol. Motor-evoked potentials were evaluated before and up to 40 min after each cPAS session as a measure of cortical excitability., Results: Compared to a single dose of cPAS, motor cortical excitability significantly increased after multi-dose cPAS. Increasing the number of cPAS sessions resulted in a cumulative, dose-dependent effect on excitability in the motor cortex, with each successive cPAS session leading to notable increases in potentiation., Conclusion: Repeated spaced cPAS sessions summate to increase motor cortical excitability induced by single cPAS., Significance: Repeated spaced cPAS could potentially restore abilities lost due to disorders like stroke., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: Identify which NIH Toolbox Cognition Battery (NIHTB-CB) subtest(s) best differentiate healthy controls (HC) from those with amnestic mild cognitive impairment (aMCI) and compare the discriminant accuracy between a model using a priori "Norm Adjusted" scores versus "Unadjusted" standard scores with age, sex, race/ethnicity, and education controlled for within the model. Racial differences were also examined., Methods: Participants were Black/African American (B/AA) and White consensus-confirmed (HC = 96; aMCI = 62) adults 60-85 years old that completed the NIHTB-CB for tablet. Discriminant function analysis (DFA) was used in the Total Sample and separately for B/AA ( n = 80) and White participants ( n = 78)., Results: Picture Sequence Memory (an episodic memory task) was the highest loading coefficient across all DFA models. When stratified by race, differences were noted in the pattern of the highest loading coefficients within the DFAs. However, the overall discriminant accuracy of the DFA models in identifying HCs and those with aMCI did not differ significantly by race (B/AA, White) or model/score type (Norm Adjusted versus Unadjusted)., Conclusions: Racial differences were noted despite the use of normalized scores or demographic covariates-highlighting the importance of including underrepresented groups in research. While the models were fairly accurate at identifying consensus-confirmed HCs, the models proved less accurate at identifying White participants with an aMCI diagnosis. In clinical settings, further work is needed to optimize computerized batteries and the use of NIHTB-CB norm adjusted scores is recommended. In research settings, demographically corrected scores or within model correction is suggested.

Only a third of individuals with mild cognitive impairment (MCI) progress to dementia of the Alzheimer's type (DAT). Identifying biomarkers that distinguish individuals with MCI who will progress to DAT (MCI-Converters) from those who will not (MCI-Non-Converters) remains a key challenge in the field. In our study, we evaluate whether the individual rates of loss of volumes of the Hippocampus and entorhinal cortex (EC) with age in the MCI stage can predict progression to DAT. Using data from 758 MCI patients in the Alzheimer's Disease Neuroimaging Database, we employ Linear Mixed Effects (LME) models to estimate individual trajectories of regional brain volume loss over 12 years on average. Our approach involves three key analyses: (1) mapping age-related volume loss trajectories in MCI-Converters and Non-Converters, (2) using logistic regression to predict progression to DAT based on individual rates of hippocampal and EC volume loss, and (3) examining the relationship between individual estimates of these volumetric changes and cognitive decline across different cognitive functions-episodic memory, visuospatial processing, and executive function. We find that the loss of Hippocampal volume is significantly more rapid in MCI-Converters than Non-Converters, but find no such difference in EC volumes. We also find that the rate of hippocampal volume loss in the MCI stage is a significant predictor of conversion to DAT, while the rate of volume loss in the EC and other additional regions is not. Finally, individual estimates of rates of regional volume loss in both the Hippocampus and EC, and other additional regions, correlate strongly with individual rates of cognitive decline. Across all analyses, we find significant individual variation in the initial volumes and the rates of changes in volume with age in individuals with MCI. This study highlights the importance of personalized approaches in predicting AD progression, offering insights for future research and intervention strategies., (© 2024. The Author(s).)

Most individuals with Parkinson's disease experience cognitive decline. Mounting evidence suggests this is partially caused by cholinergic denervation due to α-synuclein pathology in the cholinergic basal forebrain. Alpha-synuclein deposition causes inflammation, which can be measured with free water fraction, a diffusion MRI-derived metric of extracellular water. Prior studies have shown an association between basal forebrain integrity and cognition, cholinergic levels and cognition, and basal forebrain volume and acetylcholine, but no study has directly investigated whether basal forebrain physiology mediates the relationship between acetylcholine and cognition in Parkinson's disease. We investigated the relationship between these variables in a cross-sectional analysis of 101 individuals with Parkinson's disease. Cholinergic levels were measured using fluorine-18 fluoroethoxybenzovesamicol (18F-FEOBV) PET imaging. Cholinergic innervation regions of interest included the medial, lateral capsular and lateral perisylvian regions and the hippocampus. Brain volume and free water fraction were quantified using T1 and diffusion MRI, respectively. Cognitive measures included composites of attention/working memory, executive function, immediate memory and delayed memory. Data were entered into parallel mediation analyses with the cholinergic projection areas as predictors, cholinergic basal forebrain volume and free water fraction as mediators and each cognitive domain as outcomes. All mediation analyses controlled for age, years of education, levodopa equivalency dose and systolic blood pressure. The basal forebrain integrity metrics fully mediated the relationship between lateral capsular and lateral perisylvian acetylcholine and attention/working memory, and partially mediated the relationship between medial acetylcholine and attention/working memory. Basal forebrain integrity metrics fully mediated the relationship between medial, lateral capsular and lateral perisylvian acetylcholine and free water fraction. For all mediations in attention/working memory and executive function, the free water mediation was significant, while the volume mediation was not. The basal forebrain integrity metrics fully mediated the relationship between hippocampal acetylcholine and delayed memory and partially mediated the relationship between lateral capsular and lateral perisylvian acetylcholine and delayed memory. The volume mediation was significant for the hippocampal and lateral perisylvian models, while free water fraction was not. Free water fraction in the cholinergic basal forebrain mediated the relationship between acetylcholine and attention/working memory and executive function, while cholinergic basal forebrain volume mediated the relationship between acetylcholine in temporal regions in memory. These findings suggest that these two metrics reflect different stages of neurodegenerative processes and add additional evidence for a relationship between pathology in the basal forebrain, acetylcholine denervation and cognitive decline in Parkinson's disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Objectives: Social isolation is a risk factor for cognitive decline and dementia. We conducted a randomized controlled clinical trial (RCT) of enhanced social interactions, hypothesizing that conversational interactions can stimulate brain functions among socially isolated older adults without dementia. We report topline results of this multisite RCT (Internet-based conversational engagement clinical trial [I-CONECT]; NCT02871921)., Research Design and Methods: The experimental group received cognitively stimulating semistructured conversations with trained interviewers via internet/webcam 4 times per week for 6 months (induction) and twice per week for an additional 6 months (maintenance). The experimental and control groups both received weekly 10 minutes telephone check-ins. Protocol modifications were required due to the coronavirus disease 2019 pandemic., Results: A total of 186 participants were randomized. After the induction period, the experimental group had higher global cognitive test scores (Montreal Cognitive Assessment [primary outcome]; 1.75 points [p = .03]) compared with the control group. After induction, experimental group participants with normal cognition had higher language-based executive function (semantic fluency test [secondary outcome]; 2.56 points [p = .03]). At the end of the maintenance period, the experimental group of mild cognitive impairment subjects had higher encoding function (Craft Story immediate recall test [secondary outcome]; 2.19 points [p = .04]). Measure of emotional well-being improved in both control and experimental groups. Resting-state functional magnetic resonance imaging showed that the experimental group had increased connectivity within the dorsal attention network relative to the control group (p = .02), but the sample size was limited., Discussion and Implications: Providing frequent stimulating conversational interactions via the internet could be an effective home-based dementia risk-reduction strategy against social isolation and cognitive decline., Clinical Trials Registration Number: NCT02871921., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C-reactive protein (hs-CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs-CRP levels were not significantly higher in participants with mild cognitive impairment ( n  = 97) or dementia ( n  = 59), compared to those with normal cognitive function ( n  = 126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs-CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs-CRP levels, is unlikely to contribute significantly to cognitive decline., Competing Interests: SSH is a member of the scientific advisory board of Walden Biosciences. Other authors do not have a conflict of interest. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition., Objective: We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance., Methods: 112 older adults (70.7±7.3 years, range 54.6-89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer's Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models., Results: Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition., Conclusions: Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Objective: Few studies have evaluated in-home teleneuropsychological (teleNP) assessment and none, to our knowledge, has evaluated the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study evaluates the reliability of the in-home UDS v3.0 t-cog with a prior in-person UDS v3.0 evaluation., Method: One hundred and eighty-one cognitively unimpaired or cognitively impaired participants from a longitudinal study of memory and aging completed an in-person UDS v3.0 and a subsequent UDS v3.0 t-cog evaluation (∼16 months apart) administered either via video conference ( n = 122) or telephone ( n = 59)., Results: We calculated intraclass correlation coefficients (ICCs) between each time point for the entire sample. ICCs ranged widely (0.01-0.79) but were generally indicative of "moderate" (i.e., ICCs ranging from 0.5-0.75) to "good" (i.e., ICCs ranging from 0.75-0.90) agreement. Comparable ICCs were evident when looking only at those with stable diagnoses. However, relatively stronger ICCs (Range: 0.35-0.87) were found between similarly timed in-person UDS v3.0 evaluations., Conclusions: Our findings suggest that most tests on the UDS v3.0 t-cog battery may serve as a viable alternative to its in-person counterpart, though reliability may be attenuated relative to the traditional in-person format. More tightly controlled studies are needed to better establish the reliability of these measures.

Alzheimer's disease and related dementias (ADRD) present significant challenges including cognitive and functional loss, behavioral disruption, emotional distress, and significant financial burden. These stressors are amplified in minority groups, who experience higher rates of ADRD but less frequent and later diagnosis. There is therefore a critical need to identify tangible approaches to culturally informed dementia assessment and care for patients from diverse communities. Muslim patients and particularly Muslim women are among the populations most understudied in the ADRD space. Muslim patients may hold unique religious, spiritual, and cultural beliefs and practices that can impact care-seeking for dementia symptoms, diagnostic accuracy, and treatment uptake. This paper outlines culturally informed approaches to assessing and treating Muslim women and families at each stage of ADRD care, though many recommendations extend to the broader Muslim community and others of diverse racial-ethnic backgrounds. We provide concrete suggestions for building rapport within and leveraging common family structures, respecting principles of modesty and privacy for all women including those who observe hijab or niqab, and communicating dementia diagnosis and care in the context of spiritual and ethical beliefs. While not intended as a comprehensive and prescriptive guide, this review provides important points of consideration and discussion with patients of Muslim backgrounds.

Objective: The U.S. population is aging and increasing numbers of older adults are using cannabis. Cognitive decline is common in older age and subjective memory complaints (SMC) have been associated with increased risk for dementia. While residual cognitive effects of cannabis use at younger ages are well understood, the links between cannabis use and cognition in older adults is less clear. The present study represents the first population-level analysis of cannabis use and SMC in older adults in the U.S., Method: We used the National Survey of Drug Use and Health (NSDUH) dataset to evaluate SMC in respondents over age 50 (N = 26,399) according to past-year cannabis use., Results: Results revealed that 13.2% (95%CI: 11.5%-15.0%) of those who reported cannabis use also reported SMC, compared to 6.4% (95%CI: 6.1%-6.8%) among individuals with no cannabis use. Logistic regression revealed a two-fold increase (OR = 2.21, 95%CI: 1.88-2.60) of reporting SMC in respondents who had used cannabis in the past year, which was attenuated (OR = 1.38, 95%CI: 1.10-1.72) when controlling for additional factors. Other covariates, including physical health conditions, misuse of other substances, and mental illness also significantly contributed to SMC outcomes., Conclusions: Cannabis use represents a modifiable lifestyle factor that has potential for both risk and protective properties that may impact the trajectory of cognitive decline in older age. These hypothesis generating results are important for characterizing and contextualizing population-level trends related to cannabis use and SMC in older adults.

Background: Early detection is necessary for the treatment of dementia. Computerized testing has become more widely used in clinical trials; however, it is unclear how sensitive these measures are to early signs of neurodegeneration. We investigated the use of the NIH Toolbox-Cognition (NIHTB-CB) and Cogstate-Brief computerized neuropsychological batteries in the identification of mild cognitive impairment (MCI) versus healthy older adults [healthy control (HC)] and amnestic (aMCI) versus nonamnestic MCI (naMCI). Exploratory analyses include investigating potential racial differences., Methods: Two hundred six older adults were diagnosed as aMCI (n = 58), naMCI (n = 15), or cognitively healthy (HC; n = 133)., Results: The NIH Toolbox-CB subtests of Flanker, Picture Sequence Memory, and Picture Vocabulary significantly differentiated MCI from HC. Further, subtests from both computerized batteries differentiated patients with aMCI from those with naMCI. Although the main effect of race differences was noted on tests and in diagnostic groups was significant, there were no significant race-by-test interactions., Conclusions: Computer-based subtests vary in their ability to help distinguish MCI subtypes, though these tests provide less expensive and easier-to-administer clinical screeners to help identify patients early who may qualify for more comprehensive evaluations. Further work is needed, however, to refine computerized tests to achieve better precision in distinguishing impairment subtypes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Alzheimer disease (AD) biomarker testing is now common in research and approaching clinical translation. Disclosure protocols must be informed by diverse participants' perspectives on if/how the information would be useful., Methods: This study utilized semistructured interviews assessing interest in receiving positron emission tomography (PET) amyloid and tau results, as well as perceived risks and benefits of hypothetical PET disclosure as a function of race and participant diagnosis., Participants: Participants [39% Black; 61% White; Mage =74.28 (5.98)] included 57 adults diagnosed as either cognitively healthy (58%) or with mild cognitive impairment (42%) and their respective care partners [33% Black; 67% White; Mage =66.93 (10.92)]., Results: Most dyads endorsed strong interest in PET results (82.5% of both participants and partners) regardless of race or diagnosis. Black care partners were less interested in receiving the participant's results than White care partners ( χ2(4) =8.31, P =0.047). Reasons for disclosure were diverse and highly personalized, including access to treatments or clinical trials (23.2% participants; 29.8% partners), advance planning (14.3% participants; 17.5% partners), and improved health knowledge (12.5% participants; 15.8% partners). In contrast, over 80% of respondents denied any risks of disclosure., Discussion: Results suggest that predisclosure education, decisional capacity assessment, and a flexible disclosure approach are needed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Few studies have investigated tolerability, blinding, and double-blinding of High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes above 2 milliamps (mA)., Objective: We examined a) tolerability of HD-tDCS during stimulation sessions and b) blinding and double blinding of participants and study team members., Methods: Data from a mixed neurologic sample of 292 older adults were pooled from 3046 HD-tDCS sessions (2329 active; 717 sham). Per electrode amplitudes ranged from 1 mA to 4 mA with total currents up to 10 mA. Participants completed a standardized sensation (tolerability) questionnaire after each session. Participants and study team members stated whether the participant received active or sham stimulation at the end of various sessions. Data were collapsed into the presence/absence of a symptom due to low rates of positive responding and were analyzed for both differences and bioequivalency., Results: There were no safety-related adverse events. HD-tDCS was well tolerated with mostly no ("none") or "mild" sensations reported across sessions, regardless of active or sham condition and in both stimulation naïve and experienced participants. There were no significant differences in side effects between active and sham, with some achieving bioequivalence. Tingling and itching were significantly more common after lower (<2 mA) than higher (≥3 mA) amplitude active sessions, while skin redness was significantly more common after higher amplitudes. Blinding was effective at the participant and study team levels., Conclusions: HD-tDCS was well tolerated with center electrode amplitudes up to 4 mA. The bimodal ramp-up/down format of the sham was effective for blinding. These results support higher scalp-based amplitudes that enable greater brain-based current intensities in older adults., Competing Interests: Declaration of competing interest The City University of New York holds patents on brain stimulation, with MB as an inventor. MB has equity in Soterix Medical Inc. MB consults, received grants, assigned inventions, and/or served on the SAB of SafeToddles, Boston Scientific, GlaxoSmithKline, Biovisics, Mecta, Lumenis, Halo Neuroscience, Google-X, i-Lumen, Humm, Allergan (Abbvie), Apple, Ybrain, Ceragem, Remz. There are no conflicts of interest for any other author., (Published by Elsevier Inc.)

Background: Purposeful social interactions are important for healthy aging. We conducted a pilot trial of SPEAK! (Seniors Promoting English Acquisition and Knowledge), an intervention providing older volunteers with a safe, accessible opportunity to converse via webcam with English-language learners., Methods: A neurologically mixed sample of older adults was randomized to 8 weekly, webcam conversations with English-language learners or a waitlist control. Outcomes included the Cognitive Change Index (CCI) and surveys of program satisfaction. Here, we report on session completion, intervention satisfaction, and follow-up CCI scores. Exploratory analyses of CCI intervention effects controlled for baseline CCI scores and the interaction between group and baseline CCI., Results: Participants (N=38) were on average 70.8 years of age, 28/38 were White, and 16/38 demonstrated possible cognitive impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pairs completed 115/136 sessions (85%) and all volunteers said they would recommend the program. Controlling for the interaction between baseline CCI and randomization group, SPEAK! volunteers had better follow-up CCI scores than controls (P=0.018). Improvements in CCI were greater among participants with fewer baseline memory problems., Conclusions: SPEAK! was feasible and appreciated by older adults with and without cognitive impairment. Larger studies should confirm benefits for memory and other determinants of quality of life., Competing Interests: J.D.P. is a VA HSR&D Research Career Scientist. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The term cognitive training includes a range of techniques that hold potential for treating cognitive impairment caused by neurologic injury and disease. Our central premise is that these techniques differ in their mechanisms of action and therefore engage distinct brain regions (or neural networks). We support this premise using data from a single-blind randomized-controlled trial in which patients with mild cognitive impairment were randomized to either mnemonic strategy training (MST) or spaced retrieval training (SRT) as they learned ecologically relevant object-location associations. Both training approaches were highly effective in the short term, but MST demonstrated a clear advantage after days to weeks. MST also increased activation in and functional connectivity between frontal, temporal, and parietal regions as well as the hippocampus. In contrast, patterns of reduced activation and functional connectivity were evident following SRT. These findings support the rational development of cognitive training techniques., (© The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Treatments for cognitive dysfunction in neuropsychiatric conditions are urgently needed. Cognitive training and transcranial direct current stimulation (tDCS) hold promise, and there is growing interest in combined or multimodal treatments, though studies to date have had small samples and inconsistent results., Methods: A systematic review and meta-analysis was completed. Retained studies included cognitive training combined with active or sham tDCS in a neuropsychiatric population and reported a posttreatment cognitive outcome. Meta-analyses included effect sizes comparing cognitive training plus active tDCS and cognitive training plus sham tDCS in 5 cognitive domains. Risk of bias in included studies and across studies was explored., Results: Fifteen studies were included: 10 in neurodegenerative disorders and 5 in psychiatric disorders (n = 629). There were several tDCS montages, though two-thirds of studies placed the anode over the left dorsolateral prefrontal cortex. A wide variety of cognitive training types and outcome measures were reported. There was a small, statistically significant effect of combined treatment on measures of attention/working memory, as well as small and non-statistically significant effects favoring combined treatment on global cognition and language. There was no evidence of bias in individual studies but some evidence of nonreporting or small-study bias across studies., Conclusions: These results may provide preliminary support for the efficacy of combined cognitive training and tDCS on measures of attention/working memory. More data are needed, particularly via studies that explicitly align the cognitive ability of interest, stimulation target, training type, and outcome measures., (Copyright © 2022 Society of Biological Psychiatry. All rights reserved.)

Cognitive screening instruments (CSI) have variable sensitivity and specificity to the cognitive changes associated with dementia syndromes, and the most recent systematic review found insufficient evidence to support the benefit of cognitive screening tools in older adults residing within the community. Consequently, there is a critical need to improve CSI methods, which have not yet incorporated advances in psychometrics, neuroscience, and technology. The primary goal of this article is to provide a framework for transitioning from legacy CSIs to advanced dementia screening measurement. In line with ongoing efforts in neuropsychology and the call for next-generation digital assessment for early detection of AD, we propose a psychometrically advanced (including application of item response theory methods), automated selective assessment model that provides a framework to help propel an assessment revolution. Further, we present a three-phase model for modernizing CSIs and discuss critical diversity and inclusion issues, current challenges in differentiating normal from pathological aging, and ethical considerations.

Spatial navigation is essential for everyday life and relies on complex network-level interactions. Recent evidence suggests that transcranial direct current stimulation (tDCS) can influence the activity of large-scale functional brain networks. We characterized brain-wide changes in functional network segregation (i.e. the balance of within vs. between-network connectivity strength) induced by high-definition (HD) tDCS in older adults with mild cognitive impairment (MCI) during virtual spatial navigation. Twenty patients with MCI and 22 cognitively intact older adults (healthy controls-HC) underwent functional magnetic resonance imaging following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right parietal cortex (center anode at P2) and delivered 2 mA for 20 min. Compared to HC, MCI patients showed lower brain-wide network segregation following sham HD-tDCS. However, following active HD-tDCS, MCI patients' network segregation increased to levels similar to those in HC, suggesting functional normalization. Follow-up analyses indicated that the increase in network segregation for MCI patients was driven by HD-tDCS effects on the "high-level"/association brain networks, in particular the dorsal-attention and default-mode networks. HD-tDCS over the right parietal cortex may normalize the segregation/integration balance of association networks during spatial navigation in MCI patients, highlighting its potential to restore brain activity in Alzheimer's disease., (Published by Oxford University Press 2022.)

Introduction: Dual tasking impairments are an increasingly recognized contributor to falls in Parkinson disease (PD) and may be a promising therapeutic target for PD fall prevention trials. Depending on the context, ambulatory dual tasking difficulties may be caused by different types of neurocognitive impairments., Methods: We performed a cross-sectional analysis of 21 participants with PD. All participants underwent detailed neuropsychological testing that was quantified using normative z-scores. All participants completed the 3-meter timed up and go test (TUG), with and without a dual tasking assignment. Biomechanistic properties of the TUG were quantified using APDM wearable OPAL sensors. We explored correlations between dual tasking cost (DTC) in 1) total TUG duration, 2) Sit-to-stand duration, 3) Stand-to-sit duration, and 4) turn velocity., Results: Impaired total DTC in the TUG correlated inversely with global cognitive performance measured using the Montreal Cognitive Assessment (MoCA) (r = -0.4649, p = 0.0337). Sit-to-stand DTC impairments correlated inversely with processing speed on the WAIS-IV Coding (r = -0.5762, p = 0.0063), semantic fluency (r = -0.5100, p = 0.0182) and learning and memory on the Hopkins Verbal Learning Test-Revised total recall (r = -0.5502, p = 0.0098). Impaired stand-to-sit DTC function corelated inversely with visuospatial cognitive function on the Benton Judgement of Line Orientation (JOLO) test (r = -0.5181, p = 0.0161)., Conclusions: The link between dual tasking and fall risk in PD may be caused by cognitive features other than executive dysfunction and may vary based on the ambulatory task in question. These findings shed light on the cognitive contributions to falls in PD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Standardized tests of learning and memory are sensitive to changes associated with both aging and superimposed neurodegenerative diseases. Unfortunately, repeated behavioral test administration can be confounded by practice effects (PE), which may obscure declines in level of abilities and contribute to misdiagnoses. Growing evidence, however, suggests PE over successive longitudinal measurements may differentially predict cognitive status and risk for progressive decline associated with aging, mild cognitive impairment (MCI), and dementia. Thus, when viewed as a reflection of neurocognitive plasticity, PE may reveal residual abilities that can add to our understanding of age- and disease-related changes in learning and memory. The present study sought to evaluate differences in PE and verbal recall in a clinically characterized aging cohort assessed on multiple occasions over 3 years. Participants included 256 older adults recently diagnosed as cognitively unimpaired (CU; n = 126), or with MCI of amnestic ( n = 65) or non-amnestic MCI ( n = 2085), and multi-domain amnestic dementia of the Alzheimer's type (DAT; n = 45). We applied a continuous time structural equation modeling (ctsem) approach to verbal recall performance on the Hopkins Verbal Learning Test in order to distinguish PE from individual occasion performance, coupled random changes, age trends, and differing measurement quality. Diagnoses of MCI and dementia were associated with lower recall performance on all trials, reduced PE gain per occasion, and differences in non-linear dynamic parameters. Practice self-feedback is a dynamic measure of the decay or acceleration in PE process changes over longitudinal occasions. As with PE and mean recall, estimated practice self-feedback followed a gradient from positive in CU participants to null in participants with diagnosed MCI and negative for those with dementia diagnoses. Evaluation of sensitivity models showed this pattern of variation in PE was largely unmodified by differences in age, sex, or educational attainment. These results show dynamic modeling of PE from longitudinal performance on standardized learning and memory tests can capture multiple aspects of behavioral changes in MCI and dementia. The present study provides a new perspective for modeling longitudinal change in verbal learning in clinical and cognitive aging research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bender, Ganguli, Meiring, Hampstead and Driver.)

Post-anoxic leukoencephalopathy is a rare event that causes global demyelination secondary to anoxic injury. Given the nature and extent of the damage, cognitive and functional deficits are typically chronic even after standard therapies. Here, we describe a novel treatment approach that used high definition transcranial direct-current stimulation (HD-tDCS) with a 62-year-old male who was 5 years post-anoxic leukoencephalopathy secondary to an accidental drug overdose. HD-tDCS was administered over the left lateral prefrontal cortex across 29 daily sessions at 2 mA (20 min/session) in order to address dysexecutive behaviors. Results demonstrated improved delayed memory and trends for improved visuospatial and semantic fluency performance as well as improved insight and daily functioning, all of which returned to baseline by the end of a 10 week no-contact follow up period. Resting state fMRI connectivity results mirrored these changes by showing increased dorsal attention and cingulo-opercular but reduced ventral attention network connectivity after session 29, all of which returned to baseline at follow-up. These findings suggest HD-tDCS may benefit functioning even following serious and pervasive anoxic injury. Findings also suggest the need for continued HD-tDCS for maintenance purposes, though future work is needed to identify optimal dose-response information.

Objective: The objective of the study was to investigate transcranial wave propagation through two low-intensity focused ultrasound (LIFU)-based brain stimulation techniques-transcranial focused ultrasound stimulation (tFUS) and transcranial pulse stimulation (TPS). Although tFUS involves delivering long trains of acoustic pulses, the newly introduced TPS delivers ultrashort (∼3 μs) pulses repeated at 4 Hz. Accordingly, only a single simulation study with limited geometry currently exists for TPS. We considered a high-resolution three-dimensional (3D) whole human head model in addition to water bath simulations. We anticipate that the results of this study will help researchers investigating LIFU have a better understanding of the effects of the two different techniques., Approach: With an objective to first reproduce previous computational results, we considered two spherical tFUS transducers that were previously modeled. We assumed identical parameters (geometry, position, and imaging data set) to demonstrate differences, purely because of the waveform considered. For simulations with a 3D head data set, we also considered a parabolic transducer that has been used for TPS delivery., Results: Our initial results successfully verified previous modeling workflow. The tFUS distribution was characterized by the typical elliptical profile, with its major axis perpendicular to the face of the transducer. The TPS distribution resembled two mirrored meniscus profiles, with its widest diameter oriented parallel to the face of the transducer. The observed intensity value differences were theoretical because the two waveforms differ in both intensity and time. The consideration of a realistic 3D human head model resulted in only a minor distortion of the two waveforms., Significance: This study simulated TPS administration using a 3D realistic image-derived data set. Although our comparison results are strictly limited to the model parameters and assumptions made, we were able to elucidate some clear differences between the two approaches. We hope this initial study will pave the way for systematic comparison between the two approaches in the future., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Acute Respiratory Distress Syndrome (ADRS) due to coronavirus disease 2019 (COVID-19) has been associated with muscle fatigue, corticospinal pathways dysfunction, and mortality. High-Definition transcranial Direct Current Stimulation (HD-tDCS) may be used to attenuate clinical impairment in these patients. The HD-RECOVERY randomized clinical trial was conducted to evaluate the efficacy and safety of HD-tDCS with respiratory rehabilitation in patients with moderate to severe ARDS due to COVID-19., Methods: Fifty-six critically ill patients were randomized 1:1 to active (n = 28) or sham (n = 28) HD-tDCS (twice a day, 30-min, 3-mA) plus respiratory rehabilitation for up to 10 days or until intensive care unit discharge. The primary outcome was ventilator-free days during the first 28 days, defined as the number of days free from mechanical ventilation. Furthermore, secondary outcomes such as delirium, organ failure, hospital length of stay and adverse effects were investigated., Results: Active HD-tDCS induced more ventilator-free days compared to sham HD-tDCS. Patients in the active group vs in the sham group experienced lower organ dysfunction, delirium, and length of stay rates over time. In addition, positive clinical response was higher in the active vs sham group. There was no significant difference in the prespecified secondary outcomes at 5 days. Adverse events were similar between groups., Conclusions: Among patients with COVID-19 and moderate to severe ARDS, use of active HD-tDCS compared with sham HD-tDCS plus respiratory rehabilitation resulted in a statistically significant increase in the number of ventilator-free days over 28 days. HD-tDCS combined with concurrent rehabilitation therapy is a safe, feasible, potentially add-on intervention, and further trials should examine HD-tDCS efficacy in a larger sample of patients with COVID-19 and severe hypoxemia., Competing Interests: Declaration of competing interest The City University of New York holds patents on brain stimulation with MB as inventor. MB has equity in Soterix Medical Inc. MB consults, received grants, assigned inventions, and/or serves on the SAB of SafeToddles, Boston Scientific, GlaxoSmithKline, Biophysics, Mecta, Lumenis, Halo Neuroscience, Google-X, i-Lumen, Humm, Allergan (Abbvie), Apple. AD is an employee and has equity in Soterix Medical Inc., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: This study assessed the construct validity and clinical utility of the National Alzheimer's Coordinating Center Lewy Body Dementia (LBD) Module, consisting of the Speeded Attention and Noise Pareidolia Tasks., Methods: Participants included 459 older adults diagnosed as cognitively normal (n = 202), or with non-amnestic mild cognitive impairment (n = 61), amnestic mild cognitive impairment (n = 96), Alzheimer's disease dementia (n = 44), or LBD (n = 56)., Results: Speeded Attention demonstrated strong convergent validity and moderate discriminant validity when compared to established neuropsychological tests. Noise Pareidolia demonstrated strong discriminant validity, but limited convergent validity. Noise Pareidolia scores were significantly lower in those with reported hallucinations, delusions, or REM sleep behavior disorder symptoms. LBD Module tests discriminated well between cognitively normal adults and those with LBD., Discussion: The LBD Module demonstrates promising construct validity and clinical utility, which support its use across research and clinical settings., Competing Interests: None., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Purpose –: The purpose of this paper is to examine the reliability and validity of the Abbreviated Mental Test (AMT) and the agreement with the Mini-Mental State Examination (MMSE)., Design/methodology/approach –: This cross-sectional study included 446 older adults who were recruited by cluster sampling from 200,481 adults aged more than 60 years. For each participant, the AMT was administered by village health volunteers and, on a separate day, by a trained professional who also administered the MMSE. Descriptive statistics, Bland and Altman levels of agreement, and Receiver Operator Curves (ROCs) were used to analyze data., Findings –: Administration of the AMT by village health volunteers during the annual health screening found cognitive impairment in only 1.12% of the sample. When the AMT was given to these same individuals by trained professionals, the rate of cognitive impairment was almost 24 times greater. Two items in the Thai AMT may require modification due to markedly elevated failure rates. At the cut score of 8, the sensitivity and specificity of the AMT relative to the MMSE were moderate (78.83 and 66.67%, respectively). The degree of agreement between AMT and MMSE was 0.49 ( p < 0.001) and the correlation between the difference scores and the mean is exceptionally low (0.048)., Originality/value –: Reliable and valid cognitive screening assessment requires the administrator to be well trained and the tools to be appropriate for the population. Although AMT is short and easy for a nonprofessional to administer, some items were not suitable due to construct validity and contextual issues., Competing Interests: Conflict of interest: There is no conflict of interest.

Purpose/objective: Evaluate the reliability and validity of the Hopkins Rehabilitation Engagement Scale (HRERS) in a postacute rehabilitation sample. We hypothesized that HRERS items would comprise a single factor, and would demonstrate adequate internal consistency and temporal stability, and significant relationships with key constructs. Research Method and Design: Retrospective medical record review between 2016 and 2017 of older veterans ( N = 107) admitted to a community living center postacute care (CLC-PAC) rehabilitation hospital unit to address targeted physical therapy rehabilitation goals. Inclusion criteria included availability of two HRERS administrations at Time 1 (admission) and Time 2 (approximately one-month follow-up or physical therapist/CLC-PAC discharge)., Results: Across timepoints, HRERS items reflect a single factor of engagement, and the scale has good internal consistency at admission (Time 1, α = .759) and follow-up (Time 2, α = .877). The temporal stability of HRERS across ratings was r = .56 ( p < .001). Increased pain rating ( r = -.309, p < .01) and depressive symptoms (-.287, p < .01) at admission correlates with subsequent physical therapist (PT) engagement (HRERS Time 2). Low admission PT engagement correlates with less frequent PT attendance ( r = -.242, p < .01) and greater number of consults placed during the CLC stay ( r = -.222, p < .05)., Conclusions/implications: HRERS is a reliable and valid measure of PT engagement in older CLC-PAC Veterans. Findings support the administration of the HRERS at more than one timepoint during rehabilitation to inform interventions targeting select behavioral health factors such as pain and depression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Increasing social interactions through communication technologies could offer a cost-effective prevention approach that slows cognitive decline and delays the onset of Alzheimer's disease. This paper describes the protocol of an active project named "Internet-based conversational engagement clinical trial (I-CONECT)" (ClinicalTrials.gov: NCT02871921). The COVID-19 pandemic related protocol modifications are also addressed in the current paper. Methods: I-CONECT is a multi-site, assessor-blind, randomized controlled behavioral intervention trial (RCT). We aim to randomize 320 socially isolated adults 75+ years old [160 Caucasian and 160 African American participants, 50:50 split between those with normal cognition and mild cognitive impairment (MCI)] recruited from the community to either the video chat intervention group or the control group (1:1 allocation). Those in the video chat group receive a computer and Internet service for the duration of the study, which they use to video chat with study staff for 30 min/day 4×/week for 6 months (high dose), and then 2×/week for an additional 6 months (maintenance dose). Both video chat and control groups have a brief (about 10 min) telephone check-in with study staff once per week. The primary outcome is the change in global cognitive function measured by Montreal Cognitive Assessment (MoCA) from baseline to 6 months. Secondary outcomes include changes in cognition in memory and executive function domains, emotional well-being measured by NIH Toolbox emotional battery, and daily functional abilities assessed with the Revised Observed Tasks of Daily Living (OTDL-R). Eligible participants have MRIs at baseline and 6 months. Participants contribute saliva for genetic testing (optional consent), and all video chats, weekly check-in calls and neuropsychological assessment sessions are recorded for speech and language analysis. The pandemic halted research activities and resulted in protocol modifications, including replacing in-person assessment with remote assessment, remote deployment of study equipment, and revised targeted sample size. Discussion: This trial provides user-friendly hardware for the conversational-based intervention that can be easily provided at participants' homes. The trial aspires to use age and culture-specific conversational materials and a related platform developed in this trial for enhancing cognitive reserve and improving cognitive function., Competing Interests: MM was employed by company Syneos Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Wild, Potempa, Hampstead, Lichtenberg, Struble, Pruitt, Alfaro, Lindsley, MacDonald, Kaye, Silbert and Dodge.)

Systematic reviews and meta-analyses are critical in health-related decision-making, and are considered the gold standard in research synthesis methods. However, with new trials being regularly published and with the development of increasingly rigorous standards of data synthesis, systematic reviews often require much expertise and long periods of time to be completed. Automation of some of the steps of evidence synthesis productions is a promising improvement in the field, capable of reducing the time and costs associated with the process.This article describes the development and main characteristics of a novel online repository of cognitive intervention studies entitled Cognitive Treatments Article Library and Evaluation (CogTale). The platform is currently in a Beta Release phase, as it is still under development. However, it already contains over 70 studies, and the CogTale team is continuously coding and uploading new studies into the repository. Key features include advanced search options, the capability to generate meta-analyses, and an up-to-date display of relevant published studies., (© 2021. The Author(s).)

Introduction: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results., Methods: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System., Results: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols., Discussion: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The Abbreviated Mental Test is a screening tool for cognitive impairment in older adults now used in Thailand's annual national cognitive assessment required for all community-dwelling older adults in Thailand, however its validity has not been established for this purpose. This retrospective study evaluated the results of this abbreviated test as well as the Mini Mental State Examination, in a sample of older adults who participated in the national cognitive assessment in 2018 in Udon Thani Province, Thailand. Of the 174,227 cases, 1518 cases had scores on both tests. The Mini-Mental State Examination is performed on a select group of individuals who scored low on the initial and briefer test. Results indicated that the proportion of cognitive impairment as defined by the Abbreviated Mental Test (87.7%) was five times higher than indicated by the more rigorous Mini-Mental State Examination (16.3%). At the AMT standard cut point of 8 out of a total possible score of 10 for the presence of cognitive impairment, sensitivity was low (12.8%) but specificity was high (90.3%), while the optimal cut-point of 5 on the Receiver Operating Characteristic Curve errs on the side of being highly sensitive but not specific enough to screen for cognitive impairment. Additionally, one item on the AMT was answered incorrectly by 95% of responders. Although brief and easy to administer, the AMT may be a suboptimal choice for screening for cognitive impairment. When administered by volunteer health workers, the AMT may also possess limited reliability and validity. Cognitive screening administered by nurses should be considered to help detect cognitive impairment older adults dwelling in the community., Competing Interests: Disclosure statement The authors have no potential conflicts of interest to disclose

Background: Prior research, primarily with young adults, suggests transcranial direct current stimulation (tDCS) effects are driven by the primary excitatory and/or inhibitory neurotransmitters, glutamate, and gamma-aminobutyric acid (GABA), respectively., Objective: We examined the neurometabolic mechanisms of tDCS in older adults with and without mild cognitive impairment (MCI)., Methods: We used data from a double-blind, cross-over, randomized controlled trial (NCT01958437) in 32 older adults to evaluate high definition (HD)-tDCS-induced changes in glutamate and GABA via magnetic resonance spectroscopy (MRS). Participants underwent MRS following two counterbalanced HD-tDCS sessions (one active, one sham) that targeted the right superior parietal cortex (center anode at P2) and delivered 2mA for 20 minutes., Results: Relative to sham, and when co-varying for MRS voxel overlap and right superior parietal volume, active HD-tDCS significantly increased GABA and decreased the ratio of glutamate to GABA. No changes were observed in a left prefrontal control MRS voxel. Although we did not find a significant correlation between strength of delivered current (measured via MRI-based computational modeling) and neurometabolite change, there was a robust positive relationship between the volume of right superior parietal cortex and neurometabolite change., Conclusion: Our preliminary findings of increased GABA and reduced glutamate/GABA ratio raise the possibility that (HD-)tDCS effects differ by age. Moreover, age- and disease-related regional brain volume loss may be especially important to consider when planning future studies. Replication would emphasize the importance of developing population-specific tDCS parameters that consider structural and physiologic changes associated with "normal" and pathological aging.

Introduction: Mnemonic strategy training (MST) has been shown to improve cognitive performance and increase brain activation in those with mild cognitive impairment (MCI). However, little is known regarding the effects of MST on functional connectivity (FC) at rest. The aim of the present study was to investigate the MST focused on face-name associations effect on resting-state FC in those with MCI., Methods: Twenty-six amnestic MCI participants were randomized in MST (N = 14) and Education Program (active control; N = 12). Interventions occurred twice a week over two consecutive weeks (ie, four sessions). Resting-state functional magnetic resonance imaging was collected at pre- and post-intervention. Regions of interest (ROIs) were selected based on areas that previously showed task-related activation changes after MST. Changes were examined through ROI-to-ROI analysis and significant results were corrected for multiple comparisons., Results: At post-intervention, only the MST group showed increased FC, whereas the control group showed decreased or no change in FC. After MST, there was an increased FC between the left middle temporal gyrus and right orbitofrontal cortex. In addition, a time-by-group interaction indicated that the MST group showed greater increased FC between the right inferior frontal gyrus and left brain regions, such as fusiform gyrus, temporal pole, and orbitofrontal cortex relative to controls., Discussion: MST enhanced FC in regions that are functionally relevant for the training; however, not in all ROIs investigated. Our findings suggest that MST-induced changes are reflected in task-specific conditions, as previously reported, but also in general innate connectivity. Our results both enhance knowledge about the mechanisms underlying MST effects and may provide neurophysiological evidence of training transfer., Competing Interests: No author has any conflict of interest., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Prior work has revealed that mnemonic strategy training (MST) can enhance memory for specific content and engages regions in the frontoparietal cognitive control network. Evidence of transfer to novel content is less clear. Here, we provide secondary analysis of functional magnetic resonance imaging (fMRI) data acquired during a randomized controlled trial that compared MST to an active education control condition in patients with amnestic mild cognitive impairment (a-MCI). In the trial, thirty participants with a-MCI were randomized to the education program (EP) or MST, where they learned to apply the technique to face-name associations during four intervening hour long training sessions. Participants underwent pre- and post-training fMRI scans, during which they encoded both the trained (i.e., those used during the four training sessions) and untrained ('novel') face-name associations. The primary cognitive outcome measures revealed significantly improved memory for both trained and novel stimuli - effects supporting near transfer of MST. Relative to pre-training, there were significant and highly similar increases in activation for both trained and novel stimuli, especially in regions associated with the frontoparietal cognitive control network bilaterally, but also in temporal areas related to social cognition and emotional processing. Critically, this pattern of activation was notably different from the EP group. Thus, the changes in activation were consistent with the strategies trained and, combined with the cognitively-based near transfer effects, suggest that MST focused on face-name association enhances performance by engaging cognitive control and social/emotional processing. Finally, our data indicated that our MST is a relevant and efficient intervention to a-MCI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chronic Posttraumatic stress disorder (PTSD), characterized by symptoms of re-experiencing, hyperarousal, and avoidance, is challenging to treat as a significant proportion of patients remain symptomatic following even empirically supported interventions. The current case series investigated the effects of up to 10 sessions of high definition transcranial direct current stimulation (HD-tDCS) on symptoms of PTSD. Participants received HD-tDCS that targeted the right lateral temporal cortex (LTC; center cathode placed over T8), given this region's potential involvement in symptoms of re-experiencing and, possibly, hyperarousal. Five of the six enrolled patients completed at least 8 sessions. Of these five, four showed improvement in symptoms of re-experiencing after HD-tDCS. This improvement was accompanied by connectivity change in the right LTC as well as a larger extended fear network but not a control network that consisted of visual cortex regions; however, the nature of the change varied across participants as some showed increased connectivity whereas others showed decreased connectivity. These preliminary data suggest that HD-tDCS may be beneficial for treatment of specific PTSD symptoms, in at least some individuals, and warrants further investigation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Published by Elsevier B.V.)

Learning and memory deficits characterize the diagnosis of amnestic mild cognitive impairment (aMCI), which is widely viewed as a clinical precursor to Alzheimer's type dementia. There is a growing interest in non-pharmacologic interventions, such as mnemonic strategies, for improving learning and memory in patients with aMCI as well as for maintaining functioning in healthy older adults. Using an ecologically relevant object-location association paradigm, we conducted a randomized, controlled, single-blind study in which healthy older adults and patients with aMCI were randomized to either mnemonic strategy training or a control group that was matched for stimulus exposure. We previously reported that mnemonic strategy training resulted in significantly greater learning and memory improvements compared to the matched exposure condition, in both aMCI patients and healthy controls. The current study examined changes in neocortical activation during encoding in a subset of participants who underwent functional magnetic resonance imaging (fMRI) scanning both before and after training. To minimize potential confounds in between-group comparisons, we employed non-linear cortex based alignment and included only correctly encoded stimuli in our analyses. When re-encoding stimuli learned during training (i.e., trained stimuli), we found a general enhancement of activation in right prefrontal and parietal regions, possibly reflecting practice-related improvement in coordinate spatial processing in all but the aMCI exposure group. Left hemisphere activation was typically only evident in the mnemonic strategy trained participants, regardless of diagnostic status, with the ventrolateral prefrontal cortex appearing especially important for strategy use. While encoding relatively novel stimuli, both mnemonic strategy groups (aMCI patients and healthy controls) demonstrated increased activation in a subset of regions showing change for the trained stimuli, indicating a mnemonic strategy-induced change in the processing of new information. These findings could not be explained by repeated exposure since there was little to no activation overlap in the respective exposure control groups. The current results reinforce the potential benefits of cognitive interventions in these growing populations and indicate that neuroplastic change in key rostral and lateral prefrontal regions mediate this behavioral change., Competing Interests: Conflicts of interest No author has any conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Cognitive decline and dementia significantly affect independence and quality of life in older adults; therefore, it is critical to identify effective cognition-oriented treatments (COTs; eg, cognitive training, rehabilitation) that can help maintain or enhance cognitive functioning in older adults, as well as reduce dementia risk or alleviate symptoms associated with pathological processes., Methods: The Cognitive Intervention Design Evaluation and Reporting (CIDER), a working group from the Non-Pharmacological Interventions Professional Interest Area (NPI-PIA) of the Alzheimer's Association conducted as survey in 2017 with experts in COTs worldwide. The survey's aims were three-fold: (1) determine the common attitudes, beliefs, and practices of experts involved in the COTs research targeting older people; (2) identify areas of relative agreement and disagreement among experts in the field; and (3) offer a critical review of the literature, including recommendations for future research., Results: The survey identified several areas of agreements among experts on critical features of COTs, and on study design and outcome measures. Nevertheless, there were some areas with relative disagreement. Critically, expert opinions were not always supported by scientific evidence, suggesting that methodologic improvements are needed regarding design, implementation, and reporting of COTs. There was a clear consensus that COTs provide benefits and should be offered to cognitively unimpaired older adults, mild cognitive impairment (MCI), and mild dementia, but opinions differed for moderate and severe dementia. In addition, there is no consensus on the potential role of COTs in dementia prevention, indicating that future research should prioritize this aspect., Discussion: Evidence of COTs in older adults is encouraging, but additional evidence is needed to enhance dementia prevention. Consensus building and guidelines in the field are critical to improve and accelerate the development of high-quality evidence for COTs in cognitively unimpaired older adults, and those with MCI and dementia., Competing Interests: The authors declare no conflict of interest, (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Alcoholic Korsakoff's syndrome is characterized by severe amnesia, also affecting spatial memory. To date, research on cognitive rehabilitation in these patients is scarce. Aim of the present study is to examine the efficacy of a mnemonic strategy training in patients with Korsakoff's syndrome. A randomized controlled exploratory study was performed. A convenience sample of 14 patients with amnesia due to alcoholic Korsakoff's syndrome was included and randomized into a mnemonic strategy training group (n = 7) and a control group (n = 7). The training group completed a 3-day 45-60 min mnemonic strategy training that focused on specific strategies to encode and retrieve information about specific objects and their locations in virtual rooms, using labeling, verbal reasoning and mental imagery. The control group only received care as usual. Outcome measure was an object-location memory task consisting of novel, untrained object locations administered 1 day before the intervention, as well as 1 day and 1 week after completing the intervention. Patients in the intervention group were able to acquire and use the strategies, but no significant differences were found between the intervention group and the control group, and no significant change in performance was demonstrated compared to baseline 1 day and 1 week after the intervention. To conclude, the mnemonic strategy training in KS patients did not result in a better spatial memory performance 1 day or 1 week after training completion compared to participation in the regular non-cognitive treatment program that focused on occupational therapy, music therapy and exercise.

Mild cognitive impairment (MCI) is characterized by subjective and objective memory impairments within the context of generally intact everyday functioning. Such memory deficits are typically thought to arise from medial temporal lobe dysfunction; however, differences in memory task performance can arise from a variety of altered processes (e.g., strategy adjustments) rather than, or in addition to, "pure" memory deficits. To address this problem, we applied the linear ballistic accumulator (LBA: Brown and Heathcote, 2008) model to data from individuals with MCI (n = 18) and healthy older adults (HOA; n = 16) who performed an object-location association memory retrieval task during functional magnetic resonance imaging (fMRI). The primary goals were to 1) assess between-group differences in model parameters indexing processes of interest (memory sensitivity, accumulation speed, caution and time spent on peripheral perceptual and motor processes) and 2) determine whether differences in model-based metrics were consistent with fMRI data. The LBA provided evidence that, relative to the HOA group, those with MCI displayed lower sensitivity (i.e., difficulty discriminating targets from lures), suggestive of memory impairment, and displayed higher evidence accumulation speed and greater caution, suggestive of increased arousal and strategic changes in this group, although these changes had little impact on MCI-related accuracy differences. Consistent with these findings, fMRI revealed reduced activation in brain regions previously linked to evidence accumulation and to the implementation of caution reductions in the MCI group. Findings suggest that multiple cognitive mechanisms differ during memory retrieval in MCI, and that these mechanisms may explain neuroimaging alterations outside of the medial temporal lobes., (Published by Elsevier Ltd.)