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Research has shown that sensory gating is largely modualted by acetylcholine. Diminished levels of acetylcholine and sensory gating deficits have been reported in research involving Alzheimer's disease (AD) patients. However, there has been little investigation into those with a family history (FH+) of AD. The rationale of this study was to determine whether sensory gating impairments could distinguish those with early AD from individuals with increased risk for the disease while replicating previous findings of gating abnormalities in AD patients. Using the paried-click paradigm, evoked potentials were recorded from 4 groups of 20 subjects per group (AD, older controls, FH+, FH-). The results showed that while the AD group demonstrated sensory gating abnormalities, the FH+ group did not when compared to their peers with no family history of the disease (FH-). These results are discussed in relation to previous findings reporting P300 abnormalities in the FH+ group. [ABSTRACT FROM AUTHOR]

Despite their cognitive impairment, patients with mild Alzheimer's disease (AD) often make important life choices. When making choices, people frequently attempt to directly compare the features of different options, rather than evaluating each option separately. Not every feature has an analogous (or alignable) feature in the other option, however. In 2005, Mather's group found that both younger and older adults filled in such gaps when remembering, creating features in the other option to contrast with existing features. In the present study, such effects of alignability on recognition memory were not found in patients with mild AD. This finding suggests that patients with mild AD are less likely to engage in feature-by-feature comparison processes across choice options, a change that may lead them to make qualitatively different choices than healthy older adults. Copyright (c) 2006 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

There is a need to investigate exactly how memory breaks down in the course of Alzheimer's disease (AD). Examining what aspects of memorial processing remain relatively intact early in the disease process will allow us to develop behavioral interventions and possible drug therapies focused on these intact processes. Several recent studies have worked to understand the processes of recollection and familiarity in patients with mild cognitive impairment (MCI) and very mild AD. Although there is general agreement that these patient groups are relatively unable to use recollection to support veridical recognition decisions, there has been some question as to how well these patients can use familiarity. The current study used receiver operating characteristic (ROC) curves and a depth of processing manipulation to understand the effect of MCI and AD on the estimates of recollection and familiarity. Results showed that patients with MCI and AD were impaired in both recollection and familiarity, regardless of the depth of encoding. These results are discussed in relation to disease pathology and in the context of recent conflicting evidence as to whether familiarity remains intact in patients with MCI. The authors highlight differences in stimuli type and task difficulty as possibly modulating the ability of these patients to successfully use familiarity in support of memorial decisions. [ABSTRACT FROM AUTHOR]

Background: Social isolation and loneliness have both been associated with psychological health and cognitive decline in older adults. This study investigated the impact of social interaction through remote communication technologies during the COVID-19 pandemic on the cognitive and psychological status of older adults with and without cognitive impairment., Methods: Participants were recruited from Boston (USA) and Chieti (Italy). The study used a randomized single-blinded controlled crossover design with an intervention (remote social conversations with research staff over 20-minute video or telephone calls three times per week) and a passive control condition, each one of 4-weeks duration. The primary outcome was a composite cognitive score change from baseline to week 4. Secondary outcomes included scales for mood, anxiety, and loneliness., Results: Out of 196 participants recruited from April 2020 to April 2021, 17% dropped out. Based on the blind MoCA, 52% had cognitive impairment, and 25% were at risk of social isolation according to the Lubben social network scale. We observed that larger social networks were linked to better cognitive status and lower depression and anxiety levels, while loneliness was directly associated to depression severity. Older adults with cognitive impairment exhibited higher levels of depression and anxiety and were at greater risk for social isolation. In terms of the intervention, 91% preferred telephone over video calls. The intervention did not lead to improvements in cognitive or psychological scores., Conclusions: More work is needed to assess the utility of this intervention for the support of a heterogenous cross-cultural sample of older adults at-risk for social isolation, including individuals with cognitive impairment. Future research should explore longer intervention periods, categorize participants by call type, and target those meeting social isolation criteria., Trial Registration: ClinicalTrials.gov NCT04480112., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Andrew Budson has been a consultant for Eli Lilly and Genentech, and the PI on investigator-initiated trials for Vox Neuro and Bristol Myers Squibb. He also receives book royalties from Elsevier and Oxford University Press. Katherine Turk is a PI on an investigator-initiated study for Vox Neuro. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objective: To investigate the association between suspected pseudobulbar affect (PBA), clinical diagnosis, cognitive testing, and self-reported mood in older adults presenting for evaluation of dementia., Participants: Patients presenting to an outpatient memory disorders clinic (N = 311)., Methods: We used traditional and novel network modeling approaches to examine associations between neuropsychological (NP) tests, patient and clinician rating scales, and the Center for Neurological Study-Lability Scale (CNS-LS) among patients with suspected AD (n = 133) and other neurocognitive diagnosis (n = 178). We then examined differences in test performance between patients with and without suspected PBA (CNS-LS cut-off of ≥ 13), while accounting for demographic and psychiatric covariates with propensity score matching. Group differences were assessed with Bayesian models., Results: Prevalence of suspected PBA in AD was slightly less than half (44.4%) and at a similar rate in other dementias (e.g., 46.9% in CVD and 45.5% in LBD). In network models, the CNS-LS was associated with higher anxiety and better word list recall. After accounting for covariates, AD patients with suspected PBA performed better on word list recall β M  = 0.40, 95% CI [0.15, 0.66], and committed fewer false positive errors on recognition β M  = -1.51, 95% CI [-2.34, -0.59] than AD patients without suspected PBA. There were no differences in patients with any other diagnostic impression, nor group differences on other NP measures., Conclusions: Patients with suspected PBA and AD diagnosis had better memory recall and recognition than those without suspected PBA, suggesting that impaired emotional regulation may be an early sign of AD in patients with less prominent memory decline. Better understanding PBA in neurodegenerative diseases, including prevalence and comorbidity with psychiatric conditions, could help with early identification, education, and initiation of treatment., (© 2024 John Wiley & Sons Ltd.)

Background: Lecanemab and other new amyloid-targeting immunotherapies for Alzheimer disease show notable promise but may also pose significant risk for patients., Recent Findings: To facilitate the implementation and monitoring of lecanemab infusions at our tertiary medical center, we convened an interprofessional team. The team created a number of resources including patient handouts and medical documentation templates as well as systems and processes that are likely to be useful to other clinical care settings and centers., Implications for Practice: It is our intent to widely share the resources and processes developed., Competing Interests: K.W. Turk reports research funding from the Alzheimer's association, US Department of Veterans Affairs, the Doris Duke Foundation and Vox Neuro incorporated. A.E. Budson reports Eli Lilly: Consultant, VoxNeuro: investigator initiated grant, Bristol Myers Squbb: investigator initiated grant, Oxford University Press: author royalties. Elsevier: author royalties. The other authors report no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.TAKE-HOME POINTS→ An interdisciplinary team was assembled to facilitate the initial rollout of disease modifying therapies for AD.→ The team developed patient-facing and internal documents to streamline initial medication roll out effectively.→ The team also developed policies, procedures, and weekly review processes for initial eligibility screening.→ The team has developed processes for ongoing imaging and clinical review of patients receiving infusions.→ Processes and resources developed are being disseminated for use and adaptation by others., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Importance: Individuals with diabetes commonly experience Alzheimer disease and related dementias (ADRD). Factors such as hypoglycemia, hyperglycemia, and glycemic variability have been associated with increased risk of ADRD. Traditional glycemic measures, such as mean glycated hemoglobin A1c (HbA1c), may not identify the dynamic and complex pathophysiologic factors in the association between diabetes and ADRD. The HbA1c time in range (TIR) is a previously developed measure of glycemic control that expresses HbA1c stability over time within specific ranges. This measure may inform the current understanding of the association between glucose levels over time and ADRD incidence., Objective: To examine the association between HbA1c TIR and incidence of ADRD in older veterans with diabetes., Design, Setting, and Participants: The study sample for this cohort study was obtained from administrative and health care utilization data from the Veterans Health Administration and Medicare from January 1, 2004, to December 31, 2018. Veterans 65 years or older with diabetes were assessed. Participants were required to have at least 4 HbA1c tests during the 3-year baseline period, which could start between January 1, 2005, and December 31, 2014. Data analysis was conducted between July and December 2023., Main Outcomes and Measures: Hemoglobin A1c TIR was calculated as the percentage of days during baseline in which HbA1c was in individualized target ranges based on clinical characteristics and life expectancy, with higher HbA1c TIR viewed as more favorable. The association between HbA1c TIR and ADRD incidence was estimated. Additional models considered ADRD incidence in participants who were above or below HbA1c target ranges most of the time., Results: The study included 374 021 veterans with diabetes (mean [SD] age, 73.2 [5.8] years; 369 059 [99%] male). During follow-up of up to 10 years, 41 424 (11%) developed ADRD. Adjusted Cox proportional hazards regression models showed that lower HbA1c TIR was associated with increased risk of incident ADRD (HbA1c TIR of 0 to <20% compared with ≥80%: hazard ratio, 1.19; 95% CI, 1.16-1.23). Furthermore, the direction of out-of-range HbA1c levels was associated with incident ADRD. Having greater time below range (≥60%, compared with ≥60% TIR) was associated with significantly increased risk (hazard ratio, 1.23; 95% CI, 1.19-1.27). Findings remained significant after excluding individuals with baseline use of medications associated with hypoglycemia risk (ie, insulin and sulfonylureas) or with hypoglycemia events., Conclusions and Relevance: In this study of older adults with diabetes, increased HbA1c stability within patient-specific target ranges was associated with a lower risk of ADRD. Lower HbA1c TIR may identify patients at increased risk of ADRD.

Background: Spaced retrieval is a learning technique that involves engaging in repeated memory testing after increasingly lengthy intervals of time. Spaced retrieval has been shown to improve long-term memory in Alzheimer disease (AD), but it has historically been difficult to implement in the everyday lives of individuals with AD., Objective: This research aims to determine, in people with mild cognitive impairment (MCI) due to AD, the efficacy and feasibility of a mobile app that combines spaced retrieval with a machine learning algorithm to enhance memory retention. Specifically, the app prompts users to answer questions during brief daily sessions, and a machine learning algorithm tracks each user's rate of forgetting to determine the optimal spacing schedule to prevent anticipated forgetting., Methods: In this pilot study, 61 participants (young adults: n=21, 34%; healthy older adults: n=20, 33%; people with MCI due to AD: n=20, 33%) used the app for 4 weeks to learn new facts and relearn forgotten name-face associations. Participation during the 4-week period was characterized by using the app once per day to answer 15 questions about the facts and names. After the 4-week learning phase, participants completed 2 recognition memory tests approximately 1 week apart, which tested memory for information they had studied using the app as well as information they had not studied., Results: After using the mobile app for 1 month, every person with MCI due to AD demonstrated improvements in memory for new facts that they had studied via the app compared to baseline (P<.001). All but one person with MCI due to AD (19/20, 95%) showed improvements of more than 10 percentage points, comparable to the improvements shown by young adults and healthy older adults. Memory for name-face associations was similarly improved for all participant groups after using the app but to a lesser degree. Furthermore, for both new facts and name-face associations, we found no memory decay for any participant group after they took a break of approximately 1 week from using the app at the end of the study. Regarding usability, of the 20 people with MCI due to AD, 16 (80%) self-adhered to the app's automated practice schedule, and half of them (n=10, 50%) expressed an interest in continuing to use it., Conclusions: These results demonstrate early evidence that spaced retrieval mobile apps are both feasible for people with early-stage AD to use in their everyday lives and effective for supporting memory retention of recently learned facts and name-face associations., (©Amy M Smith, Anna Marin, Renee E DeCaro, Richard Feinn, Audrey Wack, Gregory I Hughes, Nathaniel Rivard, Akshay Umashankar, Katherine W Turk, Andrew E Budson. Originally published in JMIR Formative Research (https://formative.jmir.org), 19.07.2024.)

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities., Competing Interests: J.R.B. has received honoraria for continuing medical education (CME) lectures in behavioral neurology & neuropsychiatry (BNNP) and from Novo Nordisk. He has received funding from the National Institutes of Health (NIH), Dementia Alliance of North Carolina, and Alzheimer’s Association for work unrelated to this project. S.J.H. has received honoraria for CME lectures in BNNP. She has received funding from the Sidney R. Baer Jr. Foundation unrelated to this project. S.B. is a partner in and author for Brain Educators LLC, a neuropsychiatry education publisher. He has received honoraria for CME lectures in BNNP and receives a stipend as a psychiatry director of the American Board of Psychiatry and Neurology. B.F.B. receives author royalties from Cambridge University Press; honoraria for scientific advisory board activities for the Tau Consortium, funded by the Rainwater Charitable Foundation; and institutional research grant support from NIH and for clinical trials from Alector, Biogen, Transposon, Cognition Therapeutics, EIP Pharma, and GE Healthcare—all unrelated to this project. A.E.B. receives author royalties from Oxford University Press and Elsevier; investigator-initiated grants from the Alzheimer’s Association, VoxNeuro, and Bristol Myers Squibb; and consulting honorarium from Eli Lilly—all unrelated to this project. M.D.G. has consulted for Gerson Leherman Group and Reata Pharmaceuticals and receives research support from NIH, the National Institute of Neurological Disorders and Stroke (NINDS), and the Michael J. Homer Family Fund. A.E.H. receives honoraria from the American Heart Association as editor-in-chief of Stroke , and from Elsevier as associate editor of PracticeUpdate Neurology , unrelated to this project. S.K.H. has received honoraria for CME lectures from the American Academy of Neurology (AAN) and the Lewy Body Dementia Association. She has received research funding from NIH and the Michael J. Fox Foundation for Parkinson’s Research. I.K. receives funding from NIH and NINDS. J.D.S. is site principal investigator for Biohaven Pharmaceuticals clinical trials NCT03701399, NCT02960893, and NCT03952806; receives royalties from Oxford University Press, Elsevier, MacKeith Press, and Springer; and is the inventor of the Brief Ataxia Rating Scale, Cerebellar Cognitive Affective/Schmahmann Syndrome Scale, Patient Reported Outcome Measure of Ataxia, and Cerebellar Neuropsychiatry Rating Scale, which are licensed to the General Hospital Corporation. C.C.W. has received honoraria for creating educational content for the AAN. R.H.H. is a paid member of the board of trustees for the McKnight Brain Research Foundation and has received funding from NIH, the Department of Defense, and the Chan Zuckerberg Initiative for work unrelated to this project. D.L.P. has received honoraria for CME lectures in BNNP, royalties from Springer for a functional movement disorder textbook, and honoraria from Elsevier for a functional neurological disorder textbook, and is a paid member of the Brain and Behavior editorial board. He has received funding from NIH and the Sidney R. Baer Jr. Foundation unrelated to this project. The remaining authors declare no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear., Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aβ1-42, p-tau181), cognitive function, and NPS., Methods: Primary models included 781 participants from the National Alzheimer's Coordinating Center (NACC) data set who had CSF analyzed for AD biomarkers using Lumipulse. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). We assessed cognition with the harmonized MMSE/MoCA, as well as neuropsychological tests sensitive to AD pathology: story recall, naming, animal fluency, and Trails B. The Clinical Dementia Rating (CDR®) scale assessed dementia severity. Mediation models were estimated with Kemeny metric covariance in a structural equation model framework, controlling for age, education, sex, and APOEɛ4., Results: The sample was older adults (M = 73.85, SD = 6.68; 49.9% male, 390; 27.9% dementia, 218) who were predominantly white (n = 688, 88.1%). Higher p-tau181/Aβ1-42 ratio predicted higher NPI-Q, which was partially mediated by the MMSE/MoCA and, in a second model, story recall. No other pathway was statistically significant. Both the MMSE/MoCA and NPI-Q independently mediated the association between p-tau181/Aβ1-42 ratio and CDR global impairment. With dementia excluded, p-tau181/Aβ1-42 ratio was no longer associated with the NPI-Q., Conclusions: NPS may be secondary to cognitive impairment and AD pathology through direct and indirect pathways. NPS independently predict dementia severity in AD. However, AD pathology likely plays less of a role in NPS in samples without dementia.

Background: Amyloid positron emission tomography (PET) scans provide in vivo evidence of Alzheimer's disease (AD); however, their high cost limits their use in standard clinical care. Event related potentials (ERPs) may represent an inexpensive and non-invasive additional method for detecting AD pathology., Objective: We investigated whether ERPs, along with neuropsychological data, serve as predictors of amyloid PET status in patients with memory complaints., Methods: Veterans aged 50-100 were recruited from a memory disorders clinic. Participants underwent a neuropsychological battery and an ERP auditory oddball protocol. Twenty-eight patients had a positive amyloid PET scan, and thirty-nine patients had a negative scan., Results: ERP-P200 target amplitude and P200 standard latency were predictors of amyloid PET status. When submitting to ROC analysis, P200 standard latency exhibited the highest specificity and sensitivity in predicting amyloid PET positivity, correctly classifying the amyloid PET status for 86% of patients., Conclusions: ERP-P200 measures are strong indicators of amyloid-β presence in patients from a memory disorder clinic. Increased P200 amplitude and decreased P200 latency in patients with a positive amyloid PET scan may be attributed to hyperactivation of perceptual bottom-up processes compensating for AD-related synaptic loss in the fronto-parietal networks.

Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD = 69, non-AD = 54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC = 89.8), p-tau231 (AUC = 83.4), and p-tau205 (AUC = 81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR < 1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (OR p-tau217  = 15.29, OR p-tau205  = 5.05 and OR p-tau231  = 3.86) and Braak staging (OR p-tau217  = 14.29, OR p-tau205  = 5.27 and OR p-tau231  = 4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease., (© 2023. The Author(s).)

Introduction: Previous Alzheimer's disease and related dementias (AD/ADRD) research studies have illustrated the significance of studying alterations in white matter (WM). Fewer studies have examined how WM integrity, measured with diffusion tensor imaging (DTI), is associated with volume of gray matter (GM) regions and measures of cognitive function in aged participants spanning the dementia continuum., Methods: Magnetic resonance imaging and cognitive data were collected from 241 Boston University Alzheimer's Disease Research Center participants who spanned from cognitively normal controls to amnestic mild cognitive impairment to having dementia. Primary DTI tracts of interest were the cingulum ventral (CV) and cingulum dorsal (CD) pathways. GM regions of interest (ROIs) were in the medial temporal lobe (MTL), prefrontal cortex, and retrosplenial cortex. Analyses of covariance models were used to assess differences in WM integrity across groups (control, amnestic mild cognitive impairment, and dementia). Multiple linear regression models were used to assess associations between WM integrity and GM volume, and with measures of memory and executive function., Results: Differences in WM integrity were shown in both cingulum pathways in participants across the dementia continuum. Associations between WM integrity of both cingulum pathways and volume of selected GM ROIs were widespread. Functionally significant associations were found between WM of the CV pathway and memory, independent of MTL GM volume., Discussion: Differences in WM integrity of the cingulum bundle and surrounding GM ROI are likely related to the progression of AD/ADRD. Such differences should continue to be studied, particularly in association with memory performance., (© 2023 Wiley Periodicals LLC.)

Majority of dementia research is conducted in non-Hispanic White participants despite a greater prevalence of dementia in other racial groups. To obtain a better understanding of biomarker presentation of Alzheimer's disease (AD) in the non-Hispanic White population, this study exclusively examined AD biomarker abnormalities in 85 Black and/or African American participants within the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were classified by the ADNI into 3 clinical groups: cognitively normal, mild cognitive impairment, or dementia. Data examined included demographics, apolipoprotein E (APOE) ε4, cerebrospinal fluid (CSF) Aβ 1-42 , CSF total tau (t-tau), CSF phosphorylated tau (p-tau), 3T magnetic resonance imaging (MRI), and measures of cognition and function. Analyses of variance and covariance showed lower cortical thickness in 5 of 7 selected MRI regions, lower hippocampal volume, greater volume of white matter hyperintensities, lower measures of cognition and function, lower measures of CSF Aβ 1 -42 , and greater measures of CSF t-tau and p-tau between clinical groups. Our findings confirmed greater AD biomarker abnormalities between clinical groups in this sample., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The home and neighborhood environments impact the social and mental health of older adults, yet little research has addressed the various contexts that can affect these relationships, such as community culture, built and natural elements, and demographics. This survey-based study examined community-dwelling older adults' access and use of transitional outdoor/indoor space (i.e., porches, gardens, windows, etc.), and how that use was related to health variables and changed with the pandemic in two available samples of older adults in the United States and Italy. Use of both outdoor and indoor space was found to be more individualistic in Boston, in the United States, than in Chieti, Italy, where use of these areas with others was more common. Results suggest that window viewing from within the home may be an activity that individuals in Italy engage in when feeling lonely. Changes in the use of home and community space after COVID-19 were minimal; only in the United States did individuals report greater time indoors since the onset of the pandemic. Use of the built environment in and around the home by older adults was found to have multidimensional characteristics between the United States and Italy, with the potential to foster connections and improve well-being.

Introduction: This study examined plasma glial fibrillary acidic protein (GFAP) as a biomarker of cognitive impairment due to Alzheimer's disease (AD) with and against plasma neurofilament light chain (NfL), and phosphorylated tau (p-tau) 181+231 ., Methods: Plasma samples were analyzed using Simoa platform for 567 participants spanning the AD continuum. Cognitive diagnosis, neuropsychological testing, and dementia severity were examined for cross-sectional and longitudinal outcomes., Results: Plasma GFAP discriminated AD dementia from normal cognition (adjusted mean difference = 0.90 standard deviation [SD]) and mild cognitive impairment (adjusted mean difference = 0.72 SD), and demonstrated superior discrimination compared to alternative plasma biomarkers. Higher GFAP was associated with worse dementia severity and worse performance on 11 of 12 neuropsychological tests. Longitudinally, GFAP predicted decline in memory, but did not predict conversion to mild cognitive impairment or dementia., Discussion: Plasma GFAP was associated with clinical outcomes related to suspected AD and could be of assistance in a plasma biomarker panel to detect in vivo AD., Competing Interests: The authors MA, MAS, TKK, HJA, BF, YT, BM, JNP, EGS, IS, LAF, GRJ, KWT, AEB, MKO, LEG, NWK, RK, TDS, ACM, WQ, and JM have no competing interests to declare. HZ has served on scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant, on advisory boards, or on data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. NJA has given lectures in symposia sponsored by Eli‐Lily. AEB has served as a consultant or on advisory boards for Eli Lilly and Roche Pharmaceuticals and has received grant monies from Cumulus Neuroscience, VoxNeuro, Bristol Myers Squibb, and Cyclerion. He receives publishing royalties from Elsevier and Oxford University Press. RA serves on the scientific advisory board of Signant Health, as consultant to Biogen, and has given a lecture in a symposium sponsored by Eisai. RAS has served as a consultant to Biogen and Lundbeck. He receives royalties for published neuropsychological tests from Psychological Assessment Resources, Inc. MLA has received honorarium from the Michael J. Fox Foundation for services unrelated to this study. He receives royalties from Oxford University Press., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

As the rates of Alzheimer's Disease (AD) increase in the world due to the aging of the population, research has made tremendous advances to target the two hallmark pathologies of AD: amyloid-β (Aβ) plaque deposition and neurofibrillary tangles of hyperphosphorylated tau. Here, we discuss recent advances in the clinical evaluation and management of AD, with a focus on new hypotheses related to the etiology of AD and new evidence related to AD-mimicking neurodegenerative diseases. Though recent clinical studies suggest anti-amyloid disease modifying agents may slow the progression of AD, there is currently no medication that stops it. Moreover, slowing the progression will result in more individuals in the mild cognitive impairment (MCI) and mild dementia stages of AD. Given this reality, we evaluate the development of non-pharmacological strategies to help sustain cognitive function and quality of life., Competing Interests: AM has no competing interests to declare. AEB is a consultant for Eli Lilly and Genentech, and has received grant support from Bristol Myers Squibb and VoxNeuro. No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2023 Marin A et al.)

Background: Decision-making is essential to human functioning, and resolving uncertainty is an essential part of decision-making. Impaired decision-making is present in many pathological conditions, and identifying markers of decision-making under uncertainty will provide a measure of clinical impact in future studies of therapeutic intervention for impaired decision-making., Objective: To describe EEG event-related potentials (ERPs) correlating with decision-making under uncertain conditions when compared with certain conditions., Method: We used a novel card-matching task based on the Wisconsin Card Sorting Test to describe the neural correlates of uncertainty, as measured by EEG, in a group of 27 neurotypical individuals. We evaluated 500-ms intervals in the 2 seconds after card presentation to identify ERPs that are associated with maximal uncertainty compared with maximal certainty., Results: After correcting for multiple comparisons, we identified an ERP in the 500-1000-ms time frame (certain > uncertain, max amplitude 12.73 µV, latency 914 ms) in the left posterior inferior region of the scalp. We also found a P300-like ERP in the left frontal and parietal regions in the 0-500-ms time frame when the individuals received correct versus incorrect feedback (incorrect feedback > correct feedback, max amplitude 1.625 µV, latency 339 ms)., Conclusion: We identified an ERP in the 500-1000-ms time frame (certain > uncertain) that may reflect the resolution of uncertainty, as well as a P300-like ERP when feedback is presented (incorrect feedback > correct feedback). These findings can be used in future studies to improve decision-making and resolve uncertainty on the described markers., Competing Interests: The authors declare no conflicts of interest.

This study longitudinally examined participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who underwent a conversion in amyloid-beta (Aβ) status in comparison to a group of ADNI participants who did not show a change in amyloid status over the same follow-up period. Participants included 136 ADNI dementia-free participants with 2 florbetapir positron emission tomography (PET) scans. Of these participants, 68 showed amyloid conversion as measured on florbetapir PET, and the other 68 did not. Amyloid converters and non-converters were chosen to have representative demographic data (age, education, sex, diagnostic status, and race). The amyloid converter group showed increased prevalence of APOE ε4 (p < 0.001), greater annualized percent volume loss in selected magnetic resonance imaging (MRI) regions (p < 0.05), lower cerebrospinal fluid Aβ 1-42 (p < 0.001), and greater amyloid retention (as measured by standard uptake value ratios) on florbetapir PET scans (p < 0.001) in comparison to the non-converter group. These results provide compelling evidence that important neuropathological changes are occurring alongside amyloid conversion., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of Review: In this review, we summarize the current understanding of consciousness including its neuroanatomic basis. We discuss major theories of consciousness, physical exam-based and electroencephalographic metrics used to stratify levels of consciousness, and tools used to shed light on the neural correlates of the conscious experience. Lastly, we review an expanded category of 'disorders of consciousness,' which includes disorders that impact either the level or experience of consciousness., Recent Findings: Recent studies have revealed many of the requisite EEG, ERP, and fMRI signals to predict aspects of the conscious experience. Neurological disorders that disrupt the reticular activating system can affect the level of consciousness, whereas cortical disorders from seizures and migraines to strokes and dementia may disrupt phenomenal consciousness. The recently introduced memory theory of consciousness provides a new explanation of phenomenal consciousness that may explain better than prior theories both experimental studies and the neurologist's clinical experience. Although the complete neurobiological basis of consciousness remains a mystery, recent advances have improved our understanding of the physiology underlying level of consciousness and phenomenal consciousness., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Dissemination of patient safety data is key to understanding safety events and improving the quality of patient care. However, there is limited guidance on how psychiatry residency programs can create a supportive environment in which to disclose and discuss such information. The authors developed and piloted a resident-led Patient Safety Presentation process at an Accreditation Council for Graduate Medical Education-accredited psychiatry residency program, sharing patient safety data while enhancing residents' education and engagement in patient safety., Methods: From September 2020 through February 2021, the authors convened a workgroup of psychiatry residents and faculty members to devise and conduct the presentation process. The process consisted of an introductory hour-long training of residents in patient safety concepts, followed a week later by the presentation by two psychiatry residents. The authors evaluated the pilot presentation process using pre- and post-presentation resident surveys., Results: The introductory training and the Patient Safety Presentation were included into the didactic schedules of all 32 program residents. Twenty (62.5%) and 17 (53.1%) residents completed the pre- and post-presentation surveys, respectively. Improvements were seen in residents' knowledge regarding the medical center's patient safety practices and perspectives on patient safety practices. On the post-presentation survey, all 17 residents reported overall satisfaction with the presentation., Conclusions: The piloted Patient Safety Presentation process increased psychiatry residents' knowledge of and engagement in patient safety. The development and pilot of the presentation process serve as an illustrative case study for other residency programs that are aspiring to grow this aspect of their curriculum., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: To review evidence around design interventions that influence exiting attempts in dementia care units, informing architectural and clinical practice., Background: Built environment design is recognized as important in the care and management of responsive behaviors for those living with Alzheimer's disease and other dementias in secured dementia care units (e.g., exiting attempts, agitation). The repetitious behavior of "walking with purpose" (previously termed wandering) in those with dementia has influenced safety-related architectural design components of dementia care units that decrease exiting attempts. Empirical literature addressing design interventions to prevent exiting for those with dementia is lacking and outdated., Methods: We sought to describe known design techniques through a topical analysis of experimental studies. A thorough search for empirical studies that assessed interior design interventions at exit doors within dementia care units was undertaken. The review included an extensive search for existing literature and a screening of each study identified for its relevance, quality, and applicability., Results: The experimental studies included in the review collectively assessed five interior design interventions at egress doorways: implementing horizontal and vertical floor grid patterns, mirrors, murals, conditioning responses to color cues, and camouflaging door hardware or vision panels. Why empirical studies have not continued more recently as built environment trends have shifted toward promoting meaningful and purposeful movement through design are considered. Advances in our understanding around the pathophysiology of dementia which might affect future design interventions related to egress are also identified., Conclusion: The built environment is an important part of dementia care, and further prospective research is needed on the role of design interventions in the context of exiting attempts within secured units and subsequent behavior outcomes.

We suggest that there is confusion between why consciousness developed and what additional functions, through continued evolution, it has co-opted. Consider episodic memory. If we believe that episodic memory evolved solely to accurately represent past events, it seems like a terrible system-prone to forgetting and false memories. However, if we believe that episodic memory developed to flexibly and creatively combine and rearrange memories of prior events in order to plan for the future, then it is quite a good system. We argue that consciousness originally developed as part of the episodic memory system-quite likely the part needed to accomplish that flexible recombining of information. We posit further that consciousness was subsequently co-opted to produce other functions that are not directly relevant to memory per se, such as problem-solving, abstract thinking, and language. We suggest that this theory is compatible with many phenomena, such as the slow speed and the after-the-fact order of consciousness, that cannot be explained well by other theories. We believe that our theory may have profound implications for understanding intentional action and consciousness in general. Moreover, we suggest that episodic memory and its associated memory systems of sensory, working, and semantic memory as a whole ought to be considered together as the conscious memory system in that they, together, give rise to the phenomenon of consciousness. Lastly, we suggest that the cerebral cortex is the part of the brain that makes consciousness possible, and that every cortical region contributes to this conscious memory system., Competing Interests: The authors declare no conflicts of interest.

Blood-based biomarkers such as tau phosphorylated at threonine 181 (phosphorylated-tau181) represent an accessible, cost-effective and scalable approach for the in vivo detection of Alzheimer's disease pathophysiology. Plasma-pathological correlation studies are needed to validate plasma phosphorylated-tau181 as an accurate and reliable biomarker of Alzheimer's disease neuropathological changes. This plasma-to-autopsy correlation study included participants from the Boston University Alzheimer's Disease Research Center who had a plasma sample analysed for phosphorylated-tau181 between 2008 and 2018 and donated their brain for neuropathological examination. Plasma phosphorelated-tau181 was measured with single molecule array technology. Of 103 participants, 62 (60.2%) had autopsy-confirmed Alzheimer's disease. Average time between blood draw and death was 5.6 years (standard deviation = 3.1 years). Multivariable analyses showed higher plasma phosphorylated-tau181 concentrations were associated with increased odds for having autopsy-confirmed Alzheimer's disease [AUC = 0.82, OR = 1.07, 95% CI = 1.03-1.11, P < 0.01; phosphorylated-tau standardized (z-transformed): OR = 2.98, 95% CI = 1.50-5.93, P < 0.01]. Higher plasma phosphorylated-tau181 levels were associated with increased odds for having a higher Braak stage (OR = 1.06, 95% CI = 1.02-1.09, P < 0.01) and more severe phosphorylated-tau across six cortical and subcortical brain regions (ORs = 1.03-1.06, P < 0.05). The association between plasma phosphorylated-tau181 and Alzheimer's disease was strongest in those who were demented at time of blood draw (OR = 1.25, 95%CI = 1.02-1.53), but an effect existed among the non-demented (OR = 1.05, 95% CI = 1.01-1.10). There was higher discrimination accuracy for Alzheimer's disease when blood draw occurred in years closer to death; however, higher plasma phosphorylated-tau181 levels were associated with Alzheimer's disease even when blood draw occurred >5 years from death. Ante-mortem plasma phosphorylated-tau181 concentrations were associated with Alzheimer's disease neuropathology and accurately differentiated brain donors with and without autopsy-confirmed Alzheimer's disease. These findings support plasma phosphorylated-tau181 as a scalable biomarker for the detection of Alzheimer's disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Increasing numbers of patients with Alzheimer's Disease and related disorders (ADRD) necessitates increasing numbers of clinicians to care for them. Educational programming related to community outreach with older adults may help inspire interest in future ADRD clinical careers, while increasing awareness of ADRD in the community and aiding recruitment of underrepresented participants into research studies., Method: The Boston University Alzheimer's Disease Research Center (BU ADRC) created the BU ADRC Student Ambassador Program, where medical students, graduate students, and undergraduates interested in medicine completed a curriculum during the academic year that included six educational and three outreach events, including monthly dementia-focused didactic meetings and outreach focusing on Black participant recruitment. A pre-post program survey design was implemented to assess changes in students' knowledge of and attitudes toward dementia and related disorders., Results: Between September 2015 and May 2020, thirty-seven students completed the program. Following program completion, students demonstrated increased knowledge of dementia and willingness to work with patients with dementia, as well as more positive attitudes toward patients and the role of empathy in physician practice. In terms of recruitment benefits, the students helped the BU ADRC reach older adults from underrepresented groups who could serve as participants in future research studies., Conclusions: The BU ADRC Student Ambassador Program can serve as a model for other clinical research programs who wish to encourage students to consider a career in a specific field. In addition, this model has the potential to increase enrollment of participants to research studies. We discuss limitations of our initial efforts and directions for future work to quantify the anticipated benefits for student education and participant recruitment., (© 2022. The Author(s).)

Background: Individuals with probable Alzheimer disease (AD) may perform below cutoffs on traditional, memory-based performance validity tests. Previous studies have found success using event-related potentials (ERPs) to detect feigned neurocognitive impairment in younger populations., Objective: To evaluate the utility of an auditory oddball task in conjunction with the P3b peak amplitude to distinguish probable AD from simulated dementia., Method: Twenty individuals with probable AD and 20 older healthy controls (HC) underwent an ERP auditory oddball protocol and the Test of Memory Malingering (TOMM). The HC were asked to perform honestly for one condition and to simulate dementia for the other. The individuals with probable AD were asked to perform honestly. The P3b peak amplitude and button press accuracy were collected from each participant and were analyzed to determine their effectiveness in detecting performance validity., Results: The P3b peak amplitude remained stable regardless of behavioral condition in the HC group. When combined with the TOMM Trial 2 score, the P3b peak amplitude further improved the ability to correctly differentiate individuals with probable AD from HC simulating dementia with 100% sensitivity and 90% specificity., Conclusion: The P3b peak amplitude was found to be an effective physiologic measure of cognitive impairment in individuals with probable AD compared with HC simulating dementia. When combined with the TOMM Trial 2 score, the P3b peak amplitude served as a promising performance validity measure for differentiating individuals with probable AD from HC simulating dementia., Competing Interests: The authors declare no conflicts of interest.

Introduction: We aimed to characterize the clinical impact of amyloid PET (APET) in a veteran population with cognitive decline by comparing differences in management between those who did and did not have an APET., Methods: This was a retrospective observational study. Poisson regressions and logistic regression were used for comparisons., Results: Out of 565 veterans, 197 underwent APET; positivity rate was 36.55%. Having an APET was associated with longer follow-up, and increased diagnostic variability; it was not associated with number of additional studies, cholinesterase inhibitors prescription, or referrals to research. A positive APET was associated with less diagnostic variability, fewer additional tests, greater cholinesterase inhibitor prescriptions, and more research referrals., Discussion: In a medically complex, real-world population, APET yielded lower positivity rates and was not associated with classical clinical utility variables when comparing patients with and without an APET. APET may be used more to "rule out" rather than to confirm Alzheimer's disease., Highlights: Amyloid PET was associated with longer follow-up, and higher diagnostic variability.No association was seen with cholinesterase inhibitors prescription, or referrals to research.In complex patients, expected amyloid PET positivity rates are lower than previously described.Amyloid PETs were used to "rule out" AD than to confirm the diagnosis of AD., Competing Interests: A.L.V.‐R. has no disclosures to report. K.S. has no disclosures to report. A.M. has no disclosures to report. R.W. has no disclosures to report. P.H. has no disclosures to report. R.P. has no disclosures to report. R.D. has no disclosures to report. A.B. has been a consultant  for Eli Lilly, Corium, Cognito, and Sage, and a clinical trial investigator for Biogen, Eli Lilly, vTv therapeutics, and Cognito. He is also the PI on investigator initiated trials for Biogen, Cyclerion, and Bristol Myers Squibb. Katherine Turk has no disclosures to report. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: This study assessed the ordering of amyloid positron emission tomography (PET) scans in a Veterans Affairs (VA) memory disorders clinic as part of routine clinical care, with possible implications for the extent to which ordering may occur outside of the VA in the future if covered by insurance., Methods: Clinical features predictive of ordering amyloid PET scans were retrospectively assessed; the percentage of patients who met appropriate use criteria were evaluated., Results: Among 565 veterans, 34.9% of received an amyloid PET scan and 98.0% of these were consistent with appropriate use criteria. Patients with a PET were younger and more likely to have an initial diagnosis of Alzheimer's disease (AD). Of patients without an amyloid PET scan ordered, 64.4% would have met appropriate use criteria for amyloid PET., Discussion: The majority of scans ordered were consistent with appropriate use criteria and more patients were eligible than received a scan. The current study's findings that approximately one-third of patients in a memory disorders clinic received an amyloid PET scan has implications for memory disorders clinics inside and outside of the US Veterans Health Administration., Competing Interests: Ana Vives‐Rodriguez, Kylie Schiloski, Anna Marin, Ryan Wang, Patrick Hajos, Prabhjyot Singh, Rachel Powsner, Katherine Turk, and Renee Decaro have no conflicts of interest to report. Andrew Budson has been a consultant for Eli Lilly, Corium, Cognito, and Sage; a grant recipient from Cyclerion; and a clinical trial investigator for Biogen, Eli Lilly, vTv therapeutics, and Cognito. Andrew E. Budson was supported by a VA Merit Award (CX001698). Andrew E. Budson and Katherine W. Turk were investigators on National Institutes of Health/National Institute on Aging (NIH/NIA) P30 (AG072978). Katherine W. Turk was supported by a VA Career Development Award (CX002065). Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We examined the ability of plasma hyperphosphorylated tau (p-tau) 181 to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL)., Methods: Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables., Results: Plasma p-tau 181 discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau 181 had a direct association with cognitive diagnosis in a bootstrapped GGM., Discussion: These results support plasma p-tau 181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection., (© 2021 the Alzheimer's Association.)

Imagining an event from a personal perspective has been found to be able to enhance memory for words and sentences for healthy younger adults and brain-injured patients. However, little is known about how people with amnestic mild cognitive impairment (aMCI) respond to self-imagination, in comparison to healthy older adults. In the current study, participants were asked to process a group of objects using either a self-imagination approach or a baseline strategy in which the self was not heavily involved. Self-imagination shows a mnemonic advantage over the control strategy, though this pattern emerged more clearly for healthy older adults. Furthermore, suggestive evidence indicates that cognitive ability supports self-reference benefits for healthy older adults, but not aMCI patients. These findings extended previous research to reveal the effectiveness of self-imagination for older adults using pictorial stimuli and supported the viewpoint that aMCI could qualitatively change the way that cognitive resources are engaged.

Objective: We investigated the imagination inflation effect in healthy older adults and older adults with mild cognitive impairment (MCI) to determine whether an intervention can reduce susceptibility to these distortions, with implications for daily functioning., Method: Fifty-seven older adults aged 69-90 participated. In Session 1, participants either: listened to an action statement being read, performed the action, or imagined performing the action. Actions were either functional (encountered actions of daily life; e.g., "fill the pillbox") or nonfunctional (not routinely encountered; e.g., "put the toy duck on a plate"). During Session 2, participants imagined action statements from the first session. In Session 3, participants were asked to determine whether action statements were performed during the first session. Intervention participants were instructed before the first and third sessions to attend various sensory aspects of their experience using a cue-utilization technique., Results: Memory was worse for functional compared to nonfunctional actions. For older adults with MCI, the intervention increased correct identifications of functional actions that were performed. For healthy older adults, the intervention increased source memory of functional actions that were imagined. The intervention did not impact the accuracy of nonfunctional actions or the rates of misremembering an action as having been performed., Conclusions: These initial findings supported the efficacy of a cue-utilization intervention to improve memory for functional actions in an imagination inflation effect paradigm in community-dwelling older adults. The use of such strategies represents an important first step in designing interventions that are applicable to daily life. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Cerebrospinal fluid (CSF) tau and beta-amyloid levels in chronic traumatic encephalopathy (CTE), a disease which can be clinically indistinguishable from Alzheimer's disease (AD), are largely unknown. We examined postmortem CSF analytes among participants with autopsy confirmed CTE and AD., Methods: In this cross-sectional study 192 participants from the Boston University AD Research Center, VA-BU-CLF Center, and Framingham Heart Study (FHS) had post-mortem CSF collected at autopsy. Participants were divided into pathological groups based on AD and CTE criteria, with 61 CTE participants (18 low, 43 high stage), 79 AD participants (23 low, 56 intermediate to high), 11 participants with CTE combined with AD, and 41 participants lacking both CTE and AD neuropathology. The Meso Scale Discovery immunoassay system was utilized to measure amyloid-beta (Aβ 1-40, Aβ 1-42 ) , total tau (t-tau), and phosphorylated tau (p-tau 181 and p-tau 231 ). CSF analytes were then compared across the pathological groups: no CTE/no AD (control), Low CTE, Low AD, High CTE, Intermediate/High AD, and AD+CTE., Results: Among the Low disease state groups, the Low CTE group had significantly higher levels of p-tau 231 versus the control group and compared to the Low AD group. The Low CTE group was also found to have significantly lower levels of Aβ 1-42 compared to the control group. The high CTE group had higher levels of p-tau 231 and lower levels of Aβ 1-42 compared to Intermediate/High AD group., Conclusions: Importantly, p-tau 231 and Aβ 1-42 were predictors of diagnosis of CTE vs. control and CTE vs. AD. Increased CSF p-tau 231 is a promising potentially sensitive biomarker of CTE, and CSF Aβ 1-42 needs further investigation in CTE., (© 2022. The Author(s).)

Background and Objectives: Previous research has shown that elevated blood C-reactive protein (CRP) is associated with increased Alzheimer disease (AD) risk only in APOE ε4 allele carriers; the objective of this study was to examine the interactive effects of plasma CRP and APOE genotype on cognition and AD biomarkers., Methods: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed, including APOE genotype; plasma CRP concentrations; diagnostic status (i.e., mild cognitive impairment and dementia due to AD); Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Dementia Staging Instrument scores; CSF concentrations of β-amyloid peptide (Aβ 42 ), total tau (t-Tau) and phosphorylated tau (p-Tau); and amyloid (AV45) PET imaging. Multivariable regression analyses tested the associations between plasma CRP and APOE on cognitive and biomarker outcomes., Results: Among 566 ADNI participants, 274 (48.4%) had no, 222 (39.2%) had 1, and 70 (12.4%) had 2 APOE ε 4 alleles. Among only participants who had 2 APOE ε4 alleles, elevated CRP was associated with lower MMSE score at baseline ( β [95% confidence interval] -0.52 [-1.01, -0.12]) and 12-month follow-up (β -1.09 [-1.88, -0.17]) after adjustment for sex, age, and education. The interaction of 2 APOE ε4 alleles and elevated plasma CRP was associated with increased CSF levels of t-Tau (β = 11.21, SE 3.37, p < 0.001) and p-Tau (β = +2.74, SE 1.14, p < 0.01). Among those who had no APOE ε4 alleles, elevated CRP was associated with decreased CSF t-Tau and p-Tau. These effects were stronger at the 12-month follow-up., Discussion: CRP released during peripheral inflammation could be a mediator in APOE ε4-related AD neurodegeneration and serve as a drug target for AD., (© 2021 American Academy of Neurology.)

Objective: Traumatic brain injury (TBI) and repetitive head impacts (RHI) related to blasts or contact sports are commonly reported among military service members. However, the clinical implications of remote TBI and RHI in veterans remains a challenge when evaluating older veterans at risk of neurodegenerative conditions including Alzheimer's disease (AD) and Chronic Traumatic Encephalopathy (CTE). This study aimed to test the hypothesis that veterans in a memory disorders clinic with remote head injury would be more likely to have neurodegenerative clinical diagnoses, increased rates of amyloid PET positivity, higher prevalence of cavum septum pellucidi/vergae, and alterations in event-related potential (ERP) middle latency auditory evoked potentials (MLAEPs) and long latency ERP responses compared to those without head injuries. Methods: Older veterans aged 50-100 were recruited from a memory disorders clinic at VA Boston Healthcare system with a history of head injury ( n = 72) and without head injury history ( n = 52). Patients were classified as reporting prior head injury including TBI and/or RHI exposure based on self-report and chart review. Participants underwent MRI to determine presence/absence of cavum and an ERP auditory oddball protocol. Results: The head injury group was equally likely to have a positive amyloid PET compared to the non-head injury group. Additionally, the head injury group were less likely to have a diagnosis of a neurodegenerative condition than those without head injury. P200 target amplitude and MLAEP amplitudes for standard and target tones were decreased in the head injury group compared to the non-head injury group while P3b amplitude did not differ. Conclusions: Veterans with reported remote head injury evaluated in a memory disorders clinic were not more likely to have a neurodegenerative diagnosis or imaging markers of neurodegeneration than those without head injury. Decreased P200 target and MLAEP target and standard tone amplitudes in the head injury group may be relevant as potential diagnostic markers of remote head injury., 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 © 2021 Turk, Marin, Schiloski, Vives-Rodriguez, Uppal, Suh, Dwyer, Palumbo and Budson.)

This study investigated how emotional language usage impacts self-referential effects in memory in healthy older adults and individuals with amnestic mild cognitive impairment (aMCI). To heighten self-focus, 37 healthy older adults and 22 aMCI participants narrated autobiographical memories and then encoded words using a self-referencing or a semantic strategy. We were interested in how narrating autobiographical memories impacted subsequent memory. We probed narrative language usage with the Linguistic Inquiry and Word Count text analysis program, testing the degree to which language from the narrated autobiographical memories contain emotional (positive and negative) words that predicted the self-reference effect across groups. Results indicated that higher levels of positive emotional language were related to larger self-reference effects in memory. In conclusion, narrating autobiographical memories using emotional language influenced the effectiveness of self-referencing as a memory strategy for both healthy older adults and aMCI participants., 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., (© 2021 The Authors.)

Objective: Patients with mild Alzheimer's disease dementia are more susceptible to false memories than healthy older adults. Evidence that these patients can use cognitive strategies to reduce false memory is inconsistent., Method: In the present study, we examined the effectiveness of conservative responding and item-specific deep encoding strategies, alone and in combination, to reduce false memory in a categorized word list paradigm among participants with mild Alzheimer's disease dementia (AD), amnestic single-domain mild cognitive impairment (MCI), and healthy age-matched older controls (OCs). A battery of clinical neuropsychological measures was also administered., Results: Although use of conservative responding alone tended to reduce performance in the MCI and OC groups, both deep encoding alone and deep encoding combined with conservative strategies led to improved discrimination for both gist memory and item-specific recollection for these two groups. In the AD group, only gist memory benefited from the use of strategies, boosted equally by deep encoding alone and deep encoding combined with conservative strategies; item-specific recollection was not improved. No correlation between the use of these strategies and performance on neuropsychological measures was found., Conclusions: These results suggest that further evaluation of these strategies is warranted as they have the potential to reduce related and unrelated memory errors and increase both gist memory and item-specific recollection in healthy older adults and individuals with amnestic MCI. Patients with AD were less able to benefit from such strategies, yet were still able to use them to reduce unrelated memory errors and increase gist memory.

Clinical Alzheimer's disease (AD) trials currently face a critical shortfall of thousands of eligible participants, which inflates the duration and cost of the clinical study as well as threatens the scientific merit of promising clinical interventions. This recruitment crisis is further compounded by the fact that underrepresented and marginalized populations-particularly those identifying as a racial or ethnic minority, those with low socioeconomic status, or living in rural areas-have been historically underrepresented in ongoing AD clinical trials despite overwhelming evidence that such populations are at increased risk for developing dementia. As a result of various recruitment barriers, current AD clinical studies frequently reflect a decreasingly representative segment of the US population, which threatens the overall generalizability of these findings. The current narrative review provides an updated examination and critique of common recruitment barriers and potential solutions, as well as a discussion of theoretical approaches that may address barriers disproportionately experienced by underrepresented communities. AD clinical researchers are encouraged to take purposive action aimed at increasing diversity of enrolled AD clinical trial cohorts by actively identifying and quantifying barriers to research participation-especially recruitment barriers and health disparities that disproportionately prevent underrepresented and marginalized populations from participating in research. Furthermore, researchers are encouraged to closely track which individuals who express interest in AD research ultimately enroll in research studies to examine whether AD research participation is appropriately representative of the intended population for whom these new and novel AD interventions are being designed.

Educators are increasingly invited to present via webinars rather than in-person. Webinars offer multiple advantages over in-person presentations, including the ability to speak to participants across a wide geographic area and the possibility of reduced financial and time costs for the webinar organizer, speakers, and participants. To capitalize on these advantages, educators need strategies to present effectively using this medium. Here we provide 12 tips for effective webinar presentations based upon best practices identified in the literature and the authors' experience organizing educational webinars. The 12 tips are: (1) Learn webinar logistics, (2) Conduct a needs assessment, (3) Write specific learning objectives, (4) Attend a webinar, (5) Create clear, engaging slides, (6) Develop interactive learning activities, (7) Familiarize yourself with the technology, (8) Practice your presentation, (9) Be organized, prepared, and energetic, (10) Evaluate participant learning, (11) Learn from feedback, and (12) Share your experience with the organizer. We hope these tips help presenters improve the quality and effectiveness of their webinars.

We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37-0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49-0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35-2.79]), and correlated with all neuropsychological tests (r's = 0.13-0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10-0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To measure caregivers' and clinicians' perception of false memories in the lives of patients with memory loss due to Alzheimer's disease (AD) and mild cognitive impairment (MCI) using a novel false memories questionnaire. Our hypotheses were that false memories are occurring as often as forgetting according to clinicians and family members., Method: This prospective, questionnaire-based study consisting of 20 false memory questions paired with 20 forgetting questions had two forms: one for clinicians and the other for family members of older subjects. In total, 226 clinicians and 150 family members of 49 patients with AD, 44 patients with MCI, and 57 healthy older controls (OCs) completed the questionnaire., Results: False memories occurred nearly as often as forgetting according to clinicians and family members of patients with MCI and AD. Family members of OCs and patients with MCI reported fewer false memories compared to those of the AD group. As Mini-Mental State Examination scores decreased, the mean score increased for both forgetting and false memories. Among clinicians, correlations were observed between the dementia severity of patients seen with both forgetting and false memories questionnaire scores as well as with the impact of forgetting and false memories on daily life., Conclusion: Patients with AD experience false memories almost as frequently as they do forgetting. Given how common false memories are in AD patients, additional work is needed to understand the clinical implications of these false memories on patients' daily lives. The novel false memories questionnaire developed may be a valuable tool.

One's concept of the self can act as a schema, in some cases facilitating memory performance but in other cases making memory more prone to errors. In this study, we attempted to induce long-lasting self-reference effects through an autobiographical mode in younger and older adults, as well as patients with amnestic mild cognitive impairment (aMCI), predicting that a self-referential mode of thought would benefit memory. Participants first either recalled autobiographical memories or described three neutral photographs in a narrative condition. This was followed by a conventional self-referencing task. At retrieval, participants completed a recognition task. Contrary to our prediction, the self-referencing benefit emerged consistently under autobiographical and narrative modes across all groups. Although our findings indicate that self-referencing can benefit memory, it carries the risk of increasing false alarm rates when induced through an autobiographical mode and consequently the strategy should be utilized with caution.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that presents predominantly with impairments in learning and memory. Patients with AD are also susceptible to false memories , a clinically relevant memory distortion where a patient remembers an incorrect memory that they believe to be true. The use of cognitive strategies to improve memory performance among patients with AD by reducing false memories has taken on added importance given the lack of disease-modifying agents for AD. However, existing evidence suggests that cognitive strategies to reduce false memories in patients with AD are of limited effectiveness, although these strategies may be useful at earlier stages of the disease. The purpose of this review is to examine experimental findings of false memories and associated memory processes in patients with mild cognitive impairment due to AD and mild AD dementia. Cognitive strategies to reduce false memories in these patient populations are also reviewed. Approaches to clinically relevant future research are suggested and discussed.