bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of plasmalogen precursor supplementation on blood catalase and malondialdehyde levels in cognitively impaired persons
Authors: Goodenowe Dayan B. , Haroon Jonathan , Zielinski Margaret A. , Mahdavi Kennedy D. , Habelhah Barshen , Shtilkind Leah , Kling Mitchel A. , Jordan Sheldon E. 
Published: December 2021

AbstractBackgroundMalondialdehyde (MDA) is a metabolic byproduct of lipid peroxidation that is elevated in in the serum of Alzheimer’s patients. Catalase (CAT) enzymatically and plasmalogens (PLS) biochemically react with and neutralize hydrogen peroxide. 1‐O‐alkyl‐2,3‐diacylglycerol (ADG) PLS precursors containing docosahexaenoic acid (DHA) at the sn‐2 position have been shown to increase blood PLS and to be neuroprotective in animal models of neurodegeneration. The goal of this study was to evaluate the effect of dietary DHA‐ADG supplementation on PLS and MDA levels and CAT activity in the serum of cognitively impaired persons.MethodTwenty‐two persons (11M/11F), aged 37‐84 (average = 69) with mild to moderate cognitive impairment [CDR: 14(0.5); 4(1); 4(2)] were administered DHA‐ADG [1.0ml/day for 30 days; 2.0ml/day for 60 days; 4.0ml for 30 days, followed by a 30‐day wash‐out period]. Serum PLS, MDA, and CAT were measured at baseline and the end of each month.ResultBlood DHA‐PLS were elevated two‐fold by month 3 (2.06, 95% CI=1.64‐2.48) and remained elevated during treatment. Serum DHA‐PLS levels were positively correlated with CAT activity (R=0.32, p=2.7e‐03) and negatively correlated with MDA levels (r=0.41, p=9.3e‐05). Increased DHA‐PLS levels from baseline correlated with decreased MDA levels (r=0.42, p=6.4e‐05), but not increased CAT (r=0.02, p=0.9e‐01). DHA‐ADG supplementation significantly elevated CAT activity in persons with baseline CAT activity less than the average and significantly decreased MDA levels in persons with baseline MDA levels above the average to levels equivalent to the top and bottom 50%, respectively (p<0.05). MDA levels and CAT activity were negatively correlated (r=0.26, p=1.4e‐02).ConclusionDHA‐ADG was effective at elevating blood DHA‐PLS, reducing MDA in persons with high baseline MDA levels and increasing CAT activity in persons with low baseline CAT activity at the dosages studied. Although total serum DHA‐PLS were correlated with both MDA and CAT, DHA‐PLS elevation from baseline was only correlated with decreased MDA levels from baseline suggesting that the increased CAT effect of DHA‐PLS elevation was due to its MDA lowering effect. These observations are consistent with the known biochemical effects of PLS on peroxide neutralization and provide further mechanistic evidence regarding the protective effects of high blood PLS levels.
Feasibility of repeated administration of automated verbal‐paired‐associate memory in older adults
Authors: Kaula Alexander J , Cormack Francesca K , Taptiklis Nick 
Published: December 2021

AbstractBackgroundVerbal Paired‐Associates (VPA) has traditionally been administered in the clinic by a trained rater. Automated remote administration and scoring would enable use of this cognitive task at scale, over multiple visits, to allow detection of changes in memory abilities over time. Here, we address several key aspects in a feasibility study: First, the task must have good dynamic range, with performance not at ceiling or floor in older adults. Second, in order to be sensitive to memory changes over time, the test must show good test‐retest reliability. Third, older adults should be willing and able to carry out the task and operate the technology.Method41 Participants aged 55‐90 years were enrolled in the study using the Prolific online study tool, agreeing to take part in a repeat‐visits study lasting five days. Five parallel sets of eight word‐pair stimuli were generated based on a model which allowed memorability characteristics to be titrated such that the task difficulty would be suitable for an older‐adult population. On each day of the study, participants were emailed a link to the day’s task. We used the Neurovocalix web‐app to present word‐pairs and to automatically score their responses. A questionnaire was administered to assess the subjective experience of participants. Audio of participant responses was reviewed offline by the researcher.ResultScores showed some improvements over time, and the range of scores conformed to our expectations based on prior modelling. Test‐retest reliability was modest between first and second sessions but became much stronger from session two onwards. Participants generally enjoyed the task and were highly motivated to perform to the best of their abilities. Questionnaire responses confirmed that the majority found the task and interaction with the automated system engaging and rewarding.ConclusionThese preliminary results suggest automatic assessment of memory works for longitudinal measurement in older adults. The change in test‐retest reliability from sessions 1‐2 to sessions 2 and onwards suggests that a familiarisation phase will be important.
Patient experience and satisfaction with remote memory assessment: Responding to clinical need in times of COVID‐19 restrictions
Authors: Raczek Malgorzata , Porter Emma , Daley Stephanie , Farina Nicolas , Velayudhan Latha , Abraham Rajesh 
Published: December 2021

AbstractBackgroundThe suspension of memory services during the COVID‐19 pandemic delayed dementia diagnosis and access to early intervention. Some services responded to the challenge by developing a remote memory assessment pathway to comply with reduced social contact measures to protect vulnerable patients. The aim of the study was to establish whether remote model is considered a satisfactory experience within the context of the COVID‐19 pandemic and to understand the factors associated with patient and carer satisfaction of remote pathway.Method73 participants recruited from patients referred to memory clinic in West Sussex, who were assessed over a video or telephone. Participants completed an 11‐item questionnaire capturing satisfaction across a range of elements, contextual items (the impact of the pandemic, loneliness, previous experience of using teleconference technology and diagnosis), as well as 3 dimensions from Patient Experience Questionnaire. Descriptive statistics are reported at a whole sample level, separated by patient and carer status. A hypothesis driven set of bivariate analyses (Spearman’s rank) was used to understand the association between overall satisfaction and key independent factors across the whole sample.Results73 participants were typically older adults (M=68.5, SD=13.3) and female (n=40, 54.8%). The patient was more likely to be older, feel lonely within the past week and to have used video call software when compared to the carer (p> 0.05). Participants were generally satisfied with the remote pathway with 95.8% (n=69) agreeing or strongly agreeing with the statement “Overall, I was satisfied with the assessment”. Patients and carers did not significantly differ on any satisfaction response, apart from the ease of use of technology, in which carers were more likely to find the technology easy to use (U= 432.5; p=0.01). Worry about contracting COVID and communication experience was positively associated with overall satisfaction, whilst perceived communication barriers were significantly negatively associated with overall satisfaction.ConclusionsRemote memory assessment was a positive and satisfactory experience for most patient and carers. The remote pathway should be considered as an option available during and beyond the pandemic to improve access and patient choice of assessment modality.
Favorable cognitive effects of the BET protein inhibitor apabetalone in patients 70 and older
Authors: Johansson Jan O , Cummings Jeffrey L. , Zetterberg Henrik , Winblad Bengt , Sweeney Mike , Kulikowski Ewelina , Lebioda Kenneth , Khan Aziz , Toth Peter P. , Kalantar‐Zadeh Kam , Ginsburg Henry N. , Nicholls Stephen J. , Ray Kausik K , Schwartz Greg G 
Published: December 2021

AbstractBackgroundCognitive decline in late life including Alzheimer’s disease (AD) and vascular dementia (VaD) may be caused by epigenetic change. Bromodomain and extra‐terminal (BET) proteins are epigenetic transcriptional “readers” found to contribute to chronic disease. Apabetalone, a small molecule BET protein inhibitor for oral administration, was assessed for therapeutic effects on cognitive performance in a randomized trial of patients at high risk for cardiovascular disease (CVD).MethodIn the BETonMACE post‐Acute Coronary Syndrome trial in type 2 diabetes mellitus patients were randomized to apabetalone capsule 100 mg b.i.d. or placebo (n=2425). The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at baseline (n=464) and yearly in the embedded cognition study. In a prespecified analysis, participants were assigned to one of three groups: MoCA score ≥ 26 (normal performance), MoCA score 25 – 22 (mild cognitive impairment), and MoCA score ≤ 21 (dementia).ResultApabetalone exposure was equivalent in each of the three MoCA‐score defined groups. Apabetalone treatment over approximately two years was associated with an increased total MoCA score in participants with baseline MoCA score of ≤ 21 (p = 0.02). Onset of cognition benefit appeared after 12 months treatment. There was no significant difference in change from baseline in the treatment groups with higher MoCA scores.ConclusionIn the BETonMACE trial epigenetic BET protein inhibition by apabetalone capsule 100 mg b.i.d. vs placebo was associated with improved cognition as measured by MoCA in patients with baseline scores of < 21. It is feasible to embed cognition assessment in randomized Phase 3 CVD endpoint studies. BET protein inhibitors warrant further investigation for late life cognitive disorders.
Age and circadian rhythm‐dependent effects of M1 muscarinic acetylcholine receptor positive allosteric modulators and donepezil on sleep‐wake architecture and arousal
Authors: Russell Jason K , Bubser Michael , Newhouse Paul A , Lindsley Craig W , Jones Carrie K 
Published: December 2021

AbstractBackgroundDegeneration of basal forebrain cholinergic signaling in aging and Alzheimer's disease (AD) is linked with abnormalities in arousal, sleep/wake architecture, and cognition. While acetylcholinesterase inhibitors (AChEIs) are approved for the treatment of AD, they produce dose‐limiting adverse effects due to nonselective activation of peripheral muscarinic acetylcholine receptors (mAChRs). Selectively targeting the M1 mAChR using M1 positive allosteric modulators (PAMs) has shown promise for boosting cognitive performance and arousal across preclinical species. We evaluate the effects of the M1 PAM VU0453595 on arousal and sleep/wake architecture in aged and young mice across both the active and inactive phases of the circadian cycle. We hypothesize that dosing an M1 PAM during the active phase in aged mice will produce a greater enhancement of arousal and wakefulness, normalizing deficits observed in aged mice.MethodUtilizing electroencephalography, we examined the effects of the M1 PAM VU0453595 in comparison with the AChEI Donepezil on sleep‐wake architecture and state dependent spectral power in young and aged C57/BL6 mice following dosing in either the active or inactive phases of the circadian cycle.ResultWhen compared to young mice, aged mice displayed several alterations in normal sleep‐wake architecture; in the inactive phase, reductions in rapid eye movement (REM) sleep, while in the active phase increases in non‐REM (NREM) sleep and decreases in wakefulness. Aged mice also displayed reductions in slow delta power during NREM sleep and increased delta power during wake. In young mice, dosing with both compounds increased wakefulness and arousal during wake in the inactive phase, with reduced effects in the active phase. In the aged mice VU0453595 increased arousal during wake in the inactive phase, and both wakefulness and arousal during wake when dosed in the active phase. Donepezil in contrast produced increased wakefulness in the inactive period, but reduced wakefulness in the active period and limited effects on arousal during wake.ConclusionThe M1 PAM VU0453595 produced increases in wakefulness and arousal in aged mice during the active phase, suggesting that selective M1 PAMs may be suitable for dosing during the active phase in aging and AD populations to normalize disruptions in wakefulness and arousal.
Plasma p‐Tau181 and p‐Tau231 offer complementary information to identify Alzheimer's disease pathophysiology
Authors: Ferreira Pamela C.L. , Brum Wagner Scheeren , Ferrari‐Souza João Pedro , Tissot Cécile , Bellaver Bruna , Therriault Joseph , Benedet Andréa Lessa , Ashton Nicholas J. , Servaes Stijn , Lussier Firoza Z. , Chamoun Mira , Stevenson Jenna , Rahmouni Nesrine , Gauthier Serge , Vanmechelen Eugeen , Zetterberg Henrik , Blennow Kaj , Zimmer Eduardo R. , Karikari Thomas K. , Rosa‐Neto Pedro , Pascoal Tharick A. 
Published: December 2021

AbstractBackgroundPathophysiological detection of Alzheimer’s disease (AD) is commonly made using cerebrospinal fluid (CSF) and positron emission tomography (PET). However, these methods are invasive and expensive, limiting their use in clinical settings Blood‐based biomarkers, mainly measuring phosphorylated tau epitopes at threonine 181 (p‐tau181), threonine 217 (p‐tau217), threonine 231 (p‐tau231), have shown promising results in detecting AD. However, it is still unknown whether the use of different plasma p‐Tau epitopes offer overlap or complementary information. Here, we tested the hypothesis that plasma p‐Tau181 and p‐Tau231 markers provide complementary information to each other to identify AD pathophysiology.MethodsPlasma p‐Tau181, p‐Tau231, [18F]AZD4694 amyloid‐PET, [18F]MK6240 tau‐PET, MRI and cognitive assessment from 284 individuals [30 cognitively unimpaired (CU) young, 155 CU), 54 mild cognitive impairment (MCI) and 38 AD] were obtained from the McGill TRIAD cohort. The individuals with diagnose of AD or MCI was classified as cognitively impaired (CI). Maximum Youden Index were used to determine cut‐offs for plasma p‐Tau181 (11.1 ng/mL) and plasma p‐Tau231 (11.8 ng/mL) considering CU young adults as controls. We classified the individual as positive or negative using plasma for each p‐Tau biomarker. Individuals were divided in the four possible groups (p‐Tau181‐/p‐Tau231‐, p‐Tau181+/p‐Tau231‐, p‐Tau181‐/p‐Tau231+ and p‐Tau181+/p‐Tau231+) and compared to assess differences in cognition and other biomarkers.ResultsPlasma p‐tau p‐Tau181 and p‐Tau231 showed moderate correlation with each other (r = 0.64, p <0.0001) (Figure 1). The p‐Tau181+/p‐Tau231+ group presented higher tau PET and amyloid PET uptake compared to groups negative for both or only one p‐tau biomarker (all p<0.01) (Figure 2A, B). Similarly, p‐Tau181+/p‐Tau231+ group showed worse cognitive performance and hippocampal atrophy than individuals with at least one p‐tau biomarker negative (Figure 2C‐E).ConclusionThese findings highlight ‐ for the first time ‐ that individuals positive for both p‐tau231 and p‐tau181 show worse cognitive performance, higher amyloid and tau burden, and lower hippocampus volume than individuals positive for only one of these markers. Our results have important implications for the use of plasma p‐tau biomarker in clinical trials and practice, suggesting that the quantification of more than one plasma p‐tau epitope may be useful to identify individuals on an AD pathway.
Preliminary analysis of qEEG during a subliminally‐primed task‐switching test in pre‐symptomatic Alzheimer’s disease
Authors: Wu Daw‐An , Adams Sara W. , Hung Shao‐Min , Rossi Iyla P. , Harrington Michael G. , Shimojo Shinsuke , Arakaki Xianghong 
Published: December 2021

AbstractBackgroundIn testing cognitively healthy (CH) participants with normal vs. pathological amyloid/tau ratios (CH‐NAT vs. CH‐PAT), we previously identified significant differences in alpha‐band markers from quantitative electroencephalography (qEEG) during a Stroop‐based task‐switching test. Using a modified version of the test, we then found that CH‐PATs and CH‐NATs were differentially susceptible to subliminal priming, leading to different effects on reaction time. Here, we applied qEEG to the latter testing paradigm. We have conducted a preliminary analysis, using data from the participants tested prior to interruption of the project by the Covid pandemic.MethodParticipants (CH‐NAT, n=19; CH‐PAT, n=27) viewed a series of Stroop stimuli (e.g. the word “red” written in blue ink), and their task was either to respond to a given stimulus’ color or its word content by pressing buttons. A trial consisted of two stimuli in sequence, and a masked subliminal priming word (“red” or “blue”) was inserted between the two stimuli. The experimental focus was the second stimulus of each trial, which was characterized as having a task which was either switched or non‐switched compared to the first stimulus, and as having a desired response that was congruent or incongruent with the subliminal prime. Event‐related desynchronization (ERD) 250‐750 ms after the second stimulus was measured in the low‐ and high‐alpha bands (αERD).ResultαERD was observed in both high and low frequency bands following second‐stimulus presentation (both p<<<0.01, in all electrode groups). However there were no significant differences in αERD magnitude between congruent and incongruent prime conditions, nor between the CH‐NAT and CH‐PAT groups (all p>0.05).ConclusionComparisons of prime congruency may be complicated by the fact that the prime can be matched or mismatched along multiple dimensions (prime word, prime location, desired response, stimulus color, stimulus word). Given that behavioral effects have been found for this experimental paradigm, we expect that differences in neural activity may be revealed eventually with more participants, a wider exploratory analysis, and/or a refinement of the experiment task.
Neurochemical signs of astrocytic and neuronal injury in acute COVID‐19 normalizes during long‐term follow‐up
Authors: Kanberg Nelly , Simrén Joel , Éden Arvid , Andersson Lars‐Magnus , Nilsson Staffan , Ashton Nicholas J. , Sundvall Pär‐Daniel , Nellgård Bengt , Blennow Kaj , Zetterberg Henrik , Gisslén Magnus 
Published: December 2021

AbstractBackgroundNeurologic manifestations are well‐recognized features of coronavirus disease 2019 (COVID‐19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We wished to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID‐19.MethodPatients with confirmed acute COVID‐19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow‐up, and blood samples were collected longitudinally. Healthy age‐matched individuals were included as controls. We analyzed plasma concentrations of neurofilament light‐chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF‐15).ResultWe recruited 100 patients with mild (n = 24), moderate (n = 28), and severe (n = 48) COVID‐19 who were followed for a median of (IQR) 225 (187–262) days. In the acute phase, patients with severe COVID‐19 had higher concentrations of NfL than all other groups (all p < 0.001) and higher GFAp than controls (p < 0.001). GFAp was also significantly increased in moderate disease (p < 0.05) compared with controls. NfL (r = 0.53, p < 0.001) and GFAp (r = 0.39, p < 0.001) correlated with GDF‐15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly included fatigue (n = 40), “brain‐fog” (n = 29), and changes in cognition (n = 25). We found no relation between persistent neurological symptoms and CNS injury biomarkers in the acute phase.ConclusionThe normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicate that post‐acute COVID‐19 neurological sequelae are not accompanied by ongoing CNS injury. Although injury biomarkers commonly increase in severe acute COVID‐19, further investigations into the causes of post‐infectious sequelae are needed.
Plasma biomarkers of neurodegeneration and neuroinflammation in hospitalized COVID‐19 patients with and without new neurological symptoms
Authors: Boutajangout Allal , Frontera Jennifer , Debure Ludovic , Vedvyas Alok , Faustin Arline , Wisniewski Thomas 
Published: December 2021

AbstractBackgroundThe COVID‐19 pandemic is an unprecedented global health care crisis. Older individuals and those with pre‐existing AD/ADRD or mild cognitive impairment are at increased risk of SARS‐CoV‐2 infection, with a higher mortality. In this study we assessed that the presence of plasma biomarkers associated with AD, neurodegeneration and neuroinflamation in older patients (>60yrs old), who were hospitalized with COVID‐19, who either had or did not have new neurological symptoms associated with infection.MethodPatients were admitted to New York University Langone Health (NYULH), with sites in Manhattan, Brooklyn and Long Island. All patients were positive for SARS‐CoV‐2 infection. Plasma from 310 patients were analyzed (158 were tested positive for SARS‐CoV‐2 with neurological symptoms and 152 were positive for SARS‐CoV‐2 without neurologic symptoms). Plasma biomarkers assays (total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1] Aβ40, Aβ42 and pTau‐181) were performed at the Biomarker Core of NYU ADRC using the SIMOA SR‐XResultThe levels of t‐tau, NfL, GFAP, and UCH‐L1 were measured using the Neurology 4‐plex A and showed a significant elevation in COVID‐19 patients with neurologic symptoms compared to COVID‐19 patients without neurological symptoms: NfL (two tailed t‐test p = 0.0003), GFAP (two tailed t‐test p = 0.0098), UCH‐L1 (two tailed t‐test p = 0.0138) and t‐tau (two tailed t‐test p = 0.04). pTau 181 was also elevated in COVID‐19 subjects with neurological symptoms (two tailed t‐test p = 0.0141). There were no significant differences with Aβ1‐40 (two tailed t‐test p = 0.33). Both Aβ1‐42 and the pTau/ Aβ42 ratio showed a significant differences in patients with neurological symptoms (two tailed t‐test p = 0.049 and p = 0.0017, respectively).ConclusionSerum biomarkers of neuronal injury, neuroinflammation and Alzheimer’s disease such as NfL, t‐tau, UCH‐L1, GFAP and pTau‐181 correlate strongly with the presence of neurological symptoms in COVID‐19 patients. These findings indicate that patients who had COVID‐19 may have an acceleration of AD/ADRD symptoms and pathology.
With challenge comes opportunity: Dementia care innovations made in senior living during COVID that will outlast the pandemic
Authors: Doyle Patrick , Smith Nathaniel 
Published: December 2021

AbstractBackgroundSenior living communities are designed to foster social engagement and a sense of community between the residents. These settings offer a variety of care services and supports that are at their core relationship‐centered and focused optimizing the health and wellness of the residents. COVID brought major disruptions to this communal environment. Residents accustomed to daily socialization and engagement were physically separated from each other and the broader community. The impact of this isolation was immediate and had a significant impact on residents’ cognitive wellness.The pressing needs of COVID forced senior living to innovate in relation to the care of people living with dementia in these communities. We will discuss how innovations to process, infection control, technology, and design were used to keep residents safe from COVID and simultaneously maintain residents’ physical and psychosocial well‐being. Finally, we look to how these COVID‐induced innovations can re‐shape the future of dementia care in senior living.