bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring therapeutic activity of Standard extract of Bacopa monnieri (Brahmi): Indian Ayurvedic Herb
Authors: Jindal Divya
Published: June 2023

Background

Alzheimer’s disease (AD) is one of the world’s most debilitating diseases, affecting over 24 million people worldwide. Many synthetic medications developed for Alzheimer’s disease were ineffective in treating the disease, however, they were able to control the symptoms to some extent. As a result, effective bioactive chemicals are in high demand. Bacopa monnieri is an Indian herb that has been used to treat a variety of neurological disorders, according to artifacts and literature (NDDs). We want to find bioactive molecules that target distinct indicators involved in the Alzheimer’s hypothesis. The goal of this study was to learn more about Bacopa monnieri’s potential to combat various AD targets.

Method

The research involved the in‐silico approach by performing docking studies of all bioactive compounds of Bacopa monnieri and target AChE, BuChE, MAO‐A, BACE1, NMDA & APOE. All the ligands of extract were selected from the database and the protein along with ligand were prepared and docking was performed using the Glide module of Schrodinger. Further, the free energy of the complex was calculated using the MM‐GBSA of the prime module. ADME and Bioactivity scores were also analyzed for further understanding.

Result

The results demonstrate free binding and free complex energies for all the phytocompounds of Bacopa monnieri. MAO‐A, AChE, BuChE, and NMDA have shown greater binding affinities than the respective controls. The good scoring compounds were further checked for their Free Energy calculations to ensure their stability. The ADMET properties and bioactivity scores revealed the best stability of the compounds in the human system.

Conclusion

The results of the study indicated that the formulations of Bacopa monnieri can be one of the potent therapeutic components against AChE, BuChE, MAO‐A, BACE1, NMDA & APOE, based on the docking scores, free energies, amino acid interactions, ADME, bioactivity, and toxicity. Amongst all, key compounds that showed good binding energies compared to controls for all the targets were L‐Arabinose, DL‐Aspartic acid, L‐Ascorbic acid, DL‐Alanine, and 2,3‐dimethylaniline. Henceforth, it is an effective therapeutic candidate for AD.
Epigenetic modulation of cognitive function: toward new treatment models
Authors: Lima‐Filho Ricardo A S , Bigio Betty , Barnhill Olivia , Sudo Felipe K , Drummond Claudia , Assunção Naima , Vanderborght Bart , Tovar‐Moll Fernanda , Mattos Paulo , Ferreira Sergio T. , McEwen Bruce S , De Felice Fernanda G. , Lourenco Mychael V. , Nasca Carla
Published: June 2023

Background

The current translational work is an outgrowth of a mechanistic framework in rodents with cognitive deficits and depressive‐like traits, wherein the levels of the pivotal mitochondrial metabolite acetyl‐L‐carnitine (LAC) are decreased and signal to the brain abnormal activity of histone acetyltransferase and expression of genes key for neuronal plasticity, such as mGlu2 (a key inhibitor of glutamate release). Yet, the role of this emerging signaling pathway of brain plasticity remains to be fully determined in subjects with cognitive impairments (CI).

Method

Here we performed ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) to measure peripheral levels of LAC and the related mitochondrial metabolite free‐carnitine in a cohort of subjects with cognitive impairments (CI, n = 29) and age‐ and sex‐matched cognitively healthy controls (HC, n = 32). Next, we performed multiple regression analysis to investigate the relationship between mitochondrial metabolism of LAC and clinical characteristics.

Result

Decreased levels of the pivotal mitochondrial metabolite LAC in subjects with CI as compared to age‐ and sex‐matched HC subjects (p = 0.02), with potential sex differences in peripheral levels of free‐carnitine (p = 0.03). Incorporation of these new measures into a canonical biomarker model improved diagnostic accuracy

Conclusion

Our new translational findings suggest that a deficiency of LAC, and potential sex differences in free‐carnitine levels, might define clinical phenotypes of CI. Ongoing studies are ascertaining the role between LAC levels, and its main metabolite free‐carnitine, in relation to specific cognitive domains.
Exploring the association between tau‐PET and Aβ‐amyloid Centiloid value using deep learning
Authors: Ruwanpathirana Gihan P , Williams Robert , Masters Colin L. , Rowe Christopher C. , Johnston Leigh A , Davey Catherine E
Published: June 2023

Background

The study of how extracellular Aβ‐amyloid (Aβ) drives intracellular, heterogeneous tau accumulation in Alzheimer’s disease has been approached using linear models under an implicit assumption of regionally independent tau accumulation (Lockhart et al, 2017; Iaccarino et al, 2017). Multivariate, non‐linear models which enable relaxation of this assumption can be used; we employed a convolutional neural network (CNN) to identify critical tau topographic changes associated with Aβ‐burden in a cohort with a range of Aβ values, and compared results with linear analyses.

Method

134 subjects with [NAV4694 (Aβ) and [MK6240 (tau) scans were considered. A CNN was trained to map normalised tau (input) to Aβ Centiloid values (CL). CNN models were interpreted using saliency maps, denoting the importance of corresponding voxels to the output. The CNN approach was compared with linear analysis by testing the following voxel‐wise models: estimating tau SUVR from Aβ CL, and saliency from Aβ CL. All models were tested with minimum cluster extent of 200 after controlling for age and sex. Occlusion analysis was used to assess the importance of CNN‐identified salient clusters, which quantified the change in output after removing salient clusters from the input tau images.

Result

The Aβ CL values were well predicted by tau topography using the CNN (training R2 = 0.86, validation R2 = 0.75, testing R2 = 0.72). Linear analysis identified widespread correlation between Aβ CL and tau‐SUVR in the brain, while CNN analysis demonstrated focal clusters in frontal lobes, middle cingulate, precuneus, postcentral gyrus and bilateral medial temporal lobes. At low Aβ levels, information from the frontal lobe, middle cingulate and precuneus regions was more predictive of Aβ CL while the information from medial temporal lobes was more predictive of high Aβ levels.

Conclusion

The nonlinear data‐driven CNN approach, relaxing the assumption of independent regional tau accumulation, has revealed new associations between tau topography and Aβ burden.
Pilot trial of Dronabinol adjunctive treatment of agitation in Alzheimer’s disease (THC‐AD)
Authors: Rosenberg Paul B. , Outen John D. , Amjad Halima , Burhanullah Haroon , Vandrey Ryan , Nowrangi Milap A. , Schultz Meghan , Isesalaya Maria , Castaneda Ricardo , Agronin Marc , Walsh Patricia , Drury Mia , Ozonsi Rosain , Cohen Leah , Wilkins James M. , Harper David G. , Forester Brent P.
Published: June 2023

Background

Agitation in Alzheimer’s Disease (Agit‐AD) is a common and troubling neuropsychiatric syndrome which adds significantly to disability and caregiver stress. Behavioral interventions lack consistent efficacy and there are no FDA‐approved medications. Neurobiological mechanisms that contribute to Agit‐AD include brain atrophy, degradation of neurotransmission, neuroinflammation, disrupted circadian rhythms, comorbidities and frailty. Agit‐AD is a major source of disease progression, patient disability, financial burden, and caregiver stress. Dronabinol is a synthetic cannabinoid (tetrahydrocannabinol, THC). Cannabinoids may improve Agit‐AD by providing protection against neuroinflammation and excitotoxicity, regulating neurotransmitters, improving comorbidities, stabilizing circadian rhythms, and increasing cerebral blood flow.

Method

THC‐AD is a three‐week placebo‐controlled, double‐blind, RCT of dronabinol (10 mg QD) in 80 patients with severe Agit‐AD. Twice daily administration maximizes daytime coverage for agitation and minimizes sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation, and being 60‐95 years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes include a change in the Pittsburgh Agitation Scale and NPI‐C Agitation/Aggression subscales.

Result

We have enrolled 58 out of targeted 80 participants (Table 1: mean age 77.8 years, 65.5% female, 87.9% Caucasian, mean education 13.8 years, 45.6% family history). On average, study participants are very cognitively impaired (Table 2: mean baseline MMSE of 8.1), very agitated (mean NPI‐C Agitation 14.6, mean NPI‐C Aggression 6.3) and in reasonable overall health (Figure 1: General Medical Health Rating, 12.1% “excellent,” 51.7% “good” and 34.5% "fair”). Recorded AEs have been tolerable (Figure 2). Due to the COVID‐19 pandemic, we expanded our inpatient trial to include outpatient enrollments and implemented hybrid visits with telemedicine to limit in‐person interactions. We also added a supplemental study to evaluate the effects of the pandemic on caregiver stress and burden. We are collaborating with additional clinical sites, increasing dementia bed capacity, and deploying recruitment strategies for outpatients, including referrals from providers and other research trials, social media ads, and virtual community outreach.

Conclusion

Safe and effective interventions for severe agitation are greatly needed. This pilot trial will help to examine the safety and efficacy of dronabinol for Agit‐AD.
Creutzfeldt‐Jakob Disease (CJD): Time from Symptom Onset Until Subnormal Magnetic Resonance Imaging (MRI) of brain
Authors: Shergelashvili Tea , Chabrashvili Tinatin
Published: June 2023

Background

Abnormal MRI of brain is one out of three supportive diagnostic criteria for CJD along with abnormal EEG and positive 14‐3‐3 protein when there is rapidly progressive dementia (RPD), myoclonus, visual or cerebellar disturbance, pyramidal or extrapyramidal dysfunction, akinetic mutism. MRI can be normal in CJD even when the symptoms are advanced posing a diagnostic challenge. The goal of this study was to review cases of RPD suspected to be due to CJD and correlate with the diagnostic findings.

Methods

Cohort of patients with RPD and/or neuropsychiatric presentation suspicious for CJD over the 10 years at our institution was identified using EPIC Slicer Dicer tool to search electronic medical records. Clinical presentation and diagnostic markers including CSF (protein 14‐3‐3, RT‐QuIC, total‐tau), MRI and EEG findings were analyzed to determine the sensitivity of each at early disease state.

Results

Total of 25 cases suspected of CJD were identified. 4 patients were confirmed to have probable CJD based on positive RT‐QuIC, protein 14‐3‐3 and elevated total‐tau. Initial suspicion for CJD was later not considered high enough to pursue CSF analysis in 4 patients. 1 patient didn’t have CSF study done due to technical error. 16 patients were tested negative for RT‐QuIC. Out of the 16 patients 4 had elevated protein 14‐3‐3, out of which 3 had elevated total‐tau. Out of 25 patients 24 had MRI, 1 couldn’t undergo MRI due to MRI incompatible cardiac pacemaker. Out of 24 patients 4 had findings suggestive of CJD on the initial MRI, 2 of them confirmed to have CJD based on CSF studies. 2 patients had normal initial MRI despite multiple symptoms of CJD. The first patient developed classic findings for CJD on repeat MRI 8 months from symptom onset and the 2nd had such MRI changes 4 months from symptom onset. These 2 patients had diagnosis confirmed by positive RT‐QuIC, 14‐3‐3 protein and elevated total‐tau.

Conclusion

While abnormal MRI findings support the diagnosis of probable CJD in the correct clinical setting, negative test results don’t exclude diagnosis of CJD. CSF markers and a repeated brain MRI are instrumental for correct CJD diagnosis.
Association between 10‐year cardiovascular mortality‐risk and neuroimaging biomarkers in the FINGER trial
Authors: Stephen Ruth , Hossain Gazi Saadmaan , Hall Anette , Barbera Mariagnese , Ngandu Tiia , Liu Yawu , Kemppainen Nina , Strandberg Timo , Antikainen Riitta , Lötjönen Jyrki , Rinne Juha O. , Tuomilehto Jaakko , Peltonen Markku , Vanninen Ritva , Soininen Hilkka , Kivipelto Miia , Solomon Alina
Published: June 2023

Background

Cardiovascular risk factors are associated with cognitive decline and dementia. Timely estimation and targeting of cardiovascular risk burden may contribute towards the prevention of cognitive decline. The cardiovascular risk scores of the European Society of Cardiology’s, SCORE (for adults up to 64 years) and SCORE‐OP (for older adults aged 65 years or more), are commonly used tool for estimation of 10‐year CVD mortality and may reflect the impact of cardiovascular risk burden on brain pathology if validated against neuroimaging biomarkers.

Method

This study investigated associations between (i) baseline SCORE/SCORE‐OP and baseline neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B‐positron emission tomography [PiB‐PET] measures) (ii) change in SCORE/SCORE‐OP and change in neuroimaging measures during the 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). FINGER targeted at‐risk older adults, aged 60‐77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB‐PET) data from baseline and 2‐year visits were used. A total of 112 participants had repeated brain MRI measures (hippocampus, total grey matter, and white matter lesion volumes, and Alzheimer’s disease signature cortical thickness). Repeated PiB‐PET scans were available for 39 participants.

Result

Preliminary results suggest that at baseline higher SCORE/SCORE‐OP, indicating increased risk of CVD mortality was significantly associated with lower hippocampus volume (estimate = ‐0.010; p = 0.004), lower total grey matter volume (estimate = ‐0.016; p = 0.007), higher white matter lesion volume (estimate = 0.048; p = 0.015), and lower AD signature cortical thickness (‐0.004; p = 0.048) but not with PiB‐PET. No significant associations were found for change in neuroimaging measures and baseline SCORE/SCORE‐OP or change in SCORE/SCORE‐OP during the 2‐year follow‐up.

Conclusion

Cardiovascular risk scores need to be validated against different brain pathology markers in diverse populations. This will enable more precise identification and estimation of dementia risk profiles, guiding at‐risk persons to precise intervention strategies, good for both, heart, and brain.
IPSC‐derived neurons with amyloid‐β treatment reflect features of Alzheimer’s disease patients
Authors: Shi Liu , Rowland Helen A , Ribe Elena Maria M , Koychev Ivan , Nevado‐Holgado Alejo J , Buckley Noel , Lovestone Simon ,   Deep and Frequent Phenotyping study
Published: June 2023

Background

There is increasing evidence showing that induced pluripotent stem cells (iPSC)‐derived brain cells recapitulate disease‐relevant processes in patients with Alzheimer’s disease (AD). However, it remains unclear to what extent iPSC‐derived neurons treated with amyloid‐β (Aβ) reflect patient Aβ burden and other endophenotypes as determined by changes in protein expression.

Method

To investigate this, we firstly generated iPSC lines from 14 individuals with AD from the Deep and Frequent Phenotyping (DFP) pilot cohort. All of these individuals had undergone clinical measures (i.e. Mini Mental Score Examination) and neuropathological measures (i.e. Aβ, p‐tau and tau). We then differentiated these lines into cortical neurons and treated them with Aβ oligomers. We collected both cell media and cell lysates and measured over 5000 proteins in these samples using SOMAscan assay. In addition, proteins in the cerebrospinal fluid (CSF) and plasma of the same individuals were also measured using the same assay.

Result

Using Wilcox test, we identified 627 proteins that were differentially expressed in neuronal cultures under Aβ oligomers treatment after multiple correction. These proteins were significantly enriched in 14 pathways such as TGF‐β signaling pathway, Ras signaling pathway and MAPK signaling pathway etc. From protein co‐expression network analysis, we identified 12 modules (ranging from 45 to 2029 proteins) in neuronal cultures. Of them, eight were significantly associated with at least one endophenotype of the amyloid/Tau/Neurodegeneration/Cognition AT(N)C framework. We further checked the replication of these modules in human. We found that eight and nine modules were significantly preserved in CSF and plasma, respectively. Furthermore, some preserved modules were also significantly associated with some AD endophenotypes including Aβ.

Conclusion

These results suggests that iPSC‐derived neurons with Aβ treatment reflect the patients’ endophenotypes, indicating that their use in capturing disease‐relevant processes in AD.
A national program to advance dementia research in Vietnam
Authors: Vu Huyen Thi Thanh , Pham Thang , Nguyen Thu Thi Hoai , Nguyen Anh Trung , Nguyen Huong , Nguyen Tuan Anh , Hinton Ladson
Published: June 2023

Background

As Vietnam and other low‐ and middle‐income countries (LMIC) experience a rapid increase in people living with Alzheimer’s disease and related dementias (ADRD), an acute need exists to strengthen research capacity to inform policy, improve care and supports, and develop of national dementia plans. We describe the development and early outcomes of an NIH/NIA‐funded national ADRD research capacity building program in Vietnam.

Method

The research capacity building program has three components: a mentored pilot grant program, research training and networking activities, and dissemination. The pilot grant program funds Vietnamese researchers for 1‐2 years to conduct research focused on ADRD research broadly defined. Each funded investigator is paired with an international expert who serves as a mentor. Grants are reviewed and scored using NIH criteria and priority is given to pilot grants with policy relevance and potential for future funding. Training and networking activities include workshops on ADRD research topics and regular meetings in conjunction with Vietnam’s annual national dementia conference. Dissemination is facilitated through targeted outreach and the creation of a national network of institutions.

Result

Over the first three years (2019‐2022) of this five year program, we reviewed 46 applications and selected 17 for funding (4‐6 per year). Funded investigators were from diverse disciplines (e.g., geriatrics, neurology, neuropsychology, nursing, pharmacy, social work) and institutions across Vietnam with projects on a range of topics, including biomarkers, prevention, diagnosis, neuropsychological assessment, family caregiver support, dementia education, and clinical trials. An international pool of high‐income country (e.g., United States, Australia, United Kingdom) mentors has been engaged and mentors paired with each funded project. Research training has included 2 workshops at national conferences and 3 webinars that have features international speakers. A network of 11 leading academic and research institutions nationwide (i.e., Northern, Central, and Southern Vietnam) has been created to facilitate dissemination. The program has adapted to meet the challenges of the COVID‐19 pandemic. Additional process and outcome assessments of the program are planned.

Conclusion

This research capacity building program is the first of its kind in Vietnam and may serve as a useful model for other LMIC.
An internet‐based support program for family caregivers of community‐dwelling people with dementia: A pre‐post pilot study
Authors: Park Myonghwa , Jung Jihye , Kim Jinju , Kim Jahyeon , Giap Thi‐Thanh‐Tinh , Dlamini Bonkhe Brian
Published: June 2023

Background

Caregivers of people with dementia faces difficulties while constantly caring for their loved ones. Providing support programs should consider for promoting their experience of caregiving, quality of care, and will lead to delay institutionalization of dementia people. Implementing onsite support programs meets obstacles during the Covid‐19 pandemic, internet‐based interventions could be considered as a potential alternative.

Methods

This is a pre‐post pilot intervention study for primary family caregivers of community‐dwelling people with dementia. The 8‐week intervention program was delivered to the participants using ZOOM meetings software. This program consisted of 8 modules (one for each week): 1) reflecting on my caregiving journey, 2) understanding about dementia as a caregiver, 3) taking care of myself, 4) managing stress, 5) communicating with others, 6) learning how to take care of dementia people, 7) pleasant daily life, and 8) planning my caregiving journey. To assess the effects of the program, five caregiver’s outcomes were measured: Positive Aspects of Caregiving, (PAC), Caregiving Self‐Efficacy Scale (CgSES), Perceived Stress Scale (PSS), Health Risk Behaviors (HRB), and satisfaction.

Results

20 caregivers participated and 18 fully completed the pilot program. The participants have the mean age is 70.6, and 3.5 years playing the role of a family caregiver. The study findings found that the program significantly improved the PAC (P = .001), PSS (P = .027), and three sub‐domains of HRB: physical health (P < .000), mental health (P = .048), and leisure activities (P = .023). Whereas, though scores of the CgSES, and three remaining sub‐domains of HRB: care difficulty, building relationships, and getting help from others were better at the posttest compared with the pretest, these changes were not statistically significant. The participants scored 4.72 (maximum is 5) for their satisfaction with the program.

Conclusion

This intervention program successfully improved quality of life and experience of the family caregivers related to their caregiving. Such online programs are a feasible solution in delivering supports to a huge subject anywhere while still mandated social distancing in this unpredictable Covid‐19 pandemic. Therefore, expanding this pilot should be considered.
The predictability and plausibility effects on N400 reflect the language deficit in patients with mild cognitive impairment
Authors: Chou Chia‐Ju , Liu Yi‐Chien , Lee Chia‐Ying
Published: June 2023

Background

Reliable markers of language decline in patients with amnesic mild cognitive impairment (aMCI) are critical for the early detection of Alzheimer’s disease. However, language impairments may be subtle and difficult to be detected from behavioral performance measures. N400 is an Event‐Related Potentials (ERP) component to index the semantic processing and has been used to reflect the deficit of language comprehension in aphasic patients (Chang et al., 2016). This study manipulated the predictability and plausibility of the Chinese classifier‐noun agreement to examine whether these two effects on N400 may serve as potential markers for the early detection of aMCI.

Method

This study recruited 16 MCI patients and 17 age‐matched healthy elders from the memory clinic of Cardinal Tian Hospital in Taiwan. All participants received [18F] florbetaben PET and a set of standardized cognitive tests, including Mini‐Mental State Examination (MMSE), verbal fluency, and Wechsler Memory Scale‐III (WMS‐III), for MCI diagnosis. The positivity rate of the aMCI group was 43.75%, and 31.25% for the healthy elder group. During the ERP recording, participants would read a series of classifier‐noun phrases, and each classifier was paired with a highly predictable, a low predictable, or an implausible noun.

Result

We performed the Linear mixed models to examine whether the predictability effect (high vs. low predictable nouns) and plausibility effect (high vs. implausible nouns) on N400 (300‐500ms) would be explained by the particpants’ cognitive performance. The data revealed that participants with higher scores of MMSE (b = ‐0.019, SE = 0.010, t = ‐1.969), verbal fluency (b = ‐0.023, SE = 0.008, t = ‐2.781), and WMS‐III (b = ‐0.002, SE = 0.001, t = ‐2.370) showed more pronounced predictability effects, which reflecting better semantic integration processing. Meanwhile, participants with poor memory engendered a reduced plausibility effect (b = ‐0.004, SE = 0.001, t = ‐3.972).

Conclusion

Our findings suggest that MCI patients would exhibit a deficit in semantic process. The predictability and plausibility effects on N400 may serve as ERPs markers to detect the language deficits in aMCI.
[18F]TRACK, a PET tracer for imaging of tropomyosin receptor kinases (Trk): Efficient radiosynthesis and preliminary evaluation in the TgF344‐AD rat model of Alzheimer’s disease
Authors: Kang Min Su , Thiel Alexander , Schirrmacher Ralf , Bernard‐Gauthier Vadim , Jaworski Carolin , Dorian Andreas , Hopewell Robert , Singleton Thomas A , Blinder Stephan , Soucy Jean‐Paul , Rosa‐Neto Pedro , Kostikov Alexey
Published: June 2023

Background

A family of tropomyosin receptor kinases (TrkA/B/C) plays important roles in the regulation of neuronal differentiation, growth, and survival via their interactions with neurotrophins. A growing body of literature suggests the downregulation of Trk in many neurodegenerative conditions of the central nervous system (CNS), including Alzheimer’s disease (AD). We recently reported the development of [18F]TRACK, the PET tracers for in vivo imaging of TrkB and its first in‐human study. Here, we wish to report a fully automated GMP‐compliant radiosynthesis of [18F]TRACK at high radiochemical purity (RCP) and molar activity and its preliminary evaluation in wild‐type and a transgenic rat model of AD.

Method

Radiosynthesis was performed using Scintomics GRP automated module via copper‐catalyzed 18F‐fluorination of the chiral boron pinacolate precursor. Brain imaging in wild‐type (n = 3) and TgF344‐AD rat models (n = 2) at 23 months was performed on microPET Concord R4 scanner.

Result

[18F]TRACK was synthesized with a 5.0±1.4% radiochemical yield not corrected for decay (activity range 95‐154 mCi) with >99% RCP and molar activities of 250 ± 75 GBq/µmol (n = 6). The synthesis was fully automated and all batches passed quality control procedures, including chemical purity, sterility and pyrogenicity. The tracer showed moderate brain uptake in wild‐type rats with the highest accumulation in the thalamus (SUVmax = 1.56 ± 0.28, 10 min post‐injection), consistent with the brain regional distribution in humans acquired in a parallel study. Preliminary data suggests lower tracer uptake in TgF344‐AD rat model of AD in thalamus, striatum and frontal cortex compared to wild‐type animals.

Conclusion

This study demonstrated the feasibility of the GMP‐compliant production of [18F]TRACK in sufficient doses and molar activities for scanning multiple subjects per day or long range deliveries. Preliminary biodistribution studies showed moderate brain uptake of the tracer with preferential accumulation in the thalamus across species. These findings warrants further studies of Trk brain expression and its implication in neurodegenerative and psychiatric pathologies using [18F]TRACK.
Age‐related hearing loss and neural correlates of visual short‐term memory
Authors: Loughrey David Gerard , Reilly Richard
Published: June 2023

Background

Age‐related hearing loss (ARHL) may be a potential modifiable risk factor for neurocognitive decline and dementia. Previous studies have reported HL is associated with decline in visual memory function. Evidence also suggests that following ARHL, there is neural reorganization in regions critical for memory. The aim of this pilot was to explore the association of ARHL with neural correlates of visual short‐term memory binding (VSTMB).

Method

Participants over the age of 65 were recruited and divided into three groups (controls (n = 14), mild HL (n = 21), and moderate or greater HL (n = 23)) based on results from a tablet‐based hearing measure. Volunteers completed the VSTMB task (shapes and binding conditions) while electroencephalography (EEG) data was synchronously recorded using a high‐density EEG array (128 scalp electrodes). Analysis was focused on comparing 5 different components (P1, N1, P2, P3, and late positive potential (LPP)) between both HL groups to controls for the memory encoding and testing phases on both shapes and binding conditions. Statistical analysis of source reconstructions (sLORETA) was also performed to explore neural regions underlying VSTMB.

Result

There was no difference between groups in behavioral performance on the VSTMB task. There were a limited number of differences in electrophysiological activity, primarily in P1, P2, P3 and LPP which increased from mild to moderate or greater HL. Analyses of source reconstructions suggested there were bilateral differences in frontal, central, parietal, temporal, and occipital neural regions between groups.

Conclusion

There were no differences in behavioral outcomes in VSTMB with HL. There may be underlying differences in neural activity on this task with greater HL which is in accordance with prior research. Further investigation into differences in neural processes underlying episodic memory with HL would be informative, particularly to examine if such differences are associated with future memory function.
An adapted version of the Three Words Three Shapes Test (3W3S) to old Brazilian adults
Authors: Silva Alice Kamensek , Zuanetti Patrícia Aparecida , Foss Maria Paula
Published: June 2023

Background

An adapted version of the Three Words Three Shapes Test (3W3S) is conducted for old Brazilian adults. This study describes the translation, back‐translation, and pilot study of 3W3S‐Br senior Brazilian adults' adaptation process.

Method

The 3W3S administration and scoring procedures were translated to Brazilian Portuguese by three independent translators. Concomitantly, a panel of specialists selected 18 abstract, regular nouns with the same amount of letters of the original format. The selected words must have had medium to high frequency in Brazilian Portuguese. They should also relate semantically and phonetically to the original ones. A final version was established and back‐translated. The 3W3S‐Br was then applied to 24 participants, divided into two groups, according to forms, of 12 members each (Form A (FA) and Form B (FB)). Inclusion criteria were age between 60‐80 years in the absence of depression, cognitive and functional impairment. The 3W3S‐Br has 5 conditions: 1) Copy (C); 2) Incidental Recall (IR); 3) Learning Trials total (LT), presented in three attempts; 4) Delayed Recall (DR); 5) Recognition (R). Correlations were verified by Pearson coefficient and differences between groups were compared by the Mann‐Whitney test. The analysis was performed by SPSS 28.0 or Windows.

Result

There were no significant associations between age (mean: 67±5), education (11±5), and sex(42%female) in all conditions of this instrument (p<0,05). Significant positive associations were demonstrated between MMSE and 3W3S‐Br in C (r = 0,481), LT (r = 0,455), DR (r = 0,407), R (r = 0,773). The comparison between alternate forms did not reveal differences in the 5 conditions of the test (p < 0,05). The groups also did not show significant differences between age, education, gender, and occurence of COVID‐19 infection.

Conclusion

Age, education, and sex did not correlate with 3W3S‐Br, whereas MEEM demonstrated correlations in most of its conditions. Alternate forms did not differ in this group of old Brazilian adults. The first steps of the adaptation process were completed and led to evidence of its clinical utility, granting further investigations. Further studies will be conducted to test psychometric properties and finalize the adaptation process.
Appropriateness of applying CSF biomarker cutoffs from Alzheimer’s disease to Parkinson’s disease
Authors: Weinshel Sarah , Irwin David J. , Zhang Panpan , Weintraub Daniel , Shaw Leslie M. , Siderowf Andrew , Xie Sharon X
Published: June 2023

Background

While cutoffs for abnormal levels of the cerebrospinal fluid (CSF) biomarkers amyloid β 1‐42 (Aβ 1‐42), total tau (t‐tau), phosphorylated tau (p‐tau), and the ratios of t‐tau/Aβ 1‐42 and p‐tau/Aβ 1‐42, have been established in Alzheimer’s disease (AD), biologically relevant cutoffs have not been studied extensively in Parkinson’s disease (PD). We aim to assess the suitability and diagnostic accuracy of established AD‐derived CSF biomarker cutoffs in the PD population.

Method

Baseline and longitudinal data on CSF biomarkers, cognitive diagnoses, and PET amyloid imaging in 423 newly diagnosed patients with PD from the Parkinson’s Progression Markers Initiative (PPMI) cohort were used to evaluate established AD biomarker cutoffs compared with optimal cutoffs derived from the PPMI cohort.

Result

Using PET amyloid imaging as the gold standard for AD pathology, the optimal cutoff of Aβ 1‐42 was higher than the AD cutoff, the optimal cutoffs of t‐tau/Aβ 1‐42 and p‐tau/Aβ 1‐42 were lower than the AD cutoffs, and their confidence intervals (CIs) did not overlap with the AD cutoffs. Optimal cutoffs for t‐tau and p‐tau to predict cognitive impairment were significantly lower than the AD cutoffs, and their CIs did not overlap with the AD cutoffs.

Conclusion

Optimal cutoffs for the PPMI cohort for Aβ 1‐42, t‐tau/Aβ 1‐42, and p‐tau/Aβ 1‐42 to predict amyloid‐PET positivity and for t‐tau and p‐tau to predict cognitive impairment differ significantly from cutoffs derived from AD populations. The presence of additional pathologies such as alpha‐synuclein in PD may lead to disease‐specific CSF biomarker characteristics.
A quantitative analysis of the impact of COVID‐19 quarantining on in‐home eating and drinking habits in a cohort of people living with dementia
Authors: Fletcher‐Lloyd Nan , Soreq Eyal , Barnaghi Payam , Kolanko Magdalena A , Wingfield David , Wilson Danielle
Published: June 2023

Background

Since the start of the coronavirus pandemic in 2019 (COVID‐19), people living with dementia (PLWD) have reported experiencing changes in their in‐home eating and drinking habits during quarantine. Previous research has been conducted solely through questionnaires, making it subject to researcher bias. However, remote monitoring technologies allow us the unprecedented ability to quantify behavioural patterns of PLWD in real‐world environments. We used data collected as part of an ongoing project at the UK Dementia Research Institute’s Care Research and Technology Centre. This work aims to understand better the effects of COVID‐19 quarantining on the in‐home eating and drinking habits of PLWD.

Method

Using COVID‐19 as a natural experiment, we compared data collated during the UK’s first COVID‐19 lockdown with the same period pre‐COVID. Household activity was observed using kitchen motion and appliance usage (refrigerator door, kettle, and oven) sensors, summed across four different daily periods (22:00, 04:00, 10:00, and 16:00), and then standardized across households by sensory device, resulting in 16 features. With this dataset, we trained a binary random forest classification model for each household independently, assessing performance using 10‐fold cross‐validation and also computing permutation feature importances (PFIs). Finally, using the PFIs of each household as a behavioural pattern reflecting in‐home eating and drinking habit changes as a function of quarantine, we used agglomerative hierarchical clustering (metric = correlation; method = ward) to identify similar behavioural changes across households.

Result

Our cohort included 25 households of PLWD. All patients (11 female : 14 male; mean age at study start = 80.3 ± 6.78 years) had established diagnoses of dementia. Across households, binary classification accuracy was high (mean = 0.88 ± 0.08), with precision and recall balanced well (mean F1‐score = 0.83 ± 0.14). Hierarchical clusters of the household PFIs produced 4 main groupings that simple statistical observations showed each relied on distinct features for binary classification.

Conclusion

Applying combined supervised and unsupervised learning approaches to in‐home monitoring data has the potential to dramatically improve research for dementia care. Our findings show that in‐home eating and drinking habit changes among PLWD, in response to the COVID‐19 quarantine, are complex.
Social determinants of health questionnaire development for patients with Alzheimer’s disease and frontotemporal dementia
Authors: Piña‐Escudero Stefanie Danielle , Possin Kate L , Tsoy Elena , Caipa Maritza Pintado , Aguirre Gloria A , Ibanez Agustin , Lanata Serggio
Published: June 2023

Background

There is a lack of instruments designed to capture exposures across various social and determinants of health throughout the lifespan in persons with late‐life neurodegenerative disorders. Responding to this need, we created and piloted the administration of the MAC‐RedLat Social Determinants of Health Questionnaire.

Method

The questionnaire was administered to 137 dyads of participants‐caregivers. An exploratory factor analysis was conducted using the software R.

Results

Participants had a mean age of 67 years (SD = 11.0). 47.7% had Alzheimer´s disease dementia and 12.4% had frontotemporal dementia, the rest were controls. Data were screened for multivariate assumptions (normality, linearity, homogeneity, and homoscedasticity). All assumptions were met with slight problems of heteroscedasticity. Bartlet’s test indicated correlation adequacy x2 = 2191.611, p<0.001, and the KMO test indicated borderline sampling adequacy, MSA = 0.75. A parallel analysis and Scree plot examination suggested 4 overall factors. Additionally, a 3‐factor model was run based on theory. Maximum likelihood examination was used with Oblimin rotation. After testing all the 37 questions, 19 items split among several factors using the criterion that loadings must be greater than .300. These items were eliminated from further analysis. The final 3‐factor model is presented in Table 1. This model achieved simple structure with each item loading on only one factor. This model had moderate fit: Tucker Lewis Index = 0.764, RMSEA = 0.062, 90%CI (0.054,0.071) and SRMR = 0.06. The CFI = 0.884 indicated room for improvement. Factor 1 included 9 items related to socioeconomic status, factor 2 included 5 items related to challenging life experiences, and factor 3 included 4 items related educational environment. The reliability of the 3 factors was 0.074, 0.071, and 0.069, for factors 1, 2, and 3 respectively. The mean scores for each factor were factor 1 M = 5.322(SD = 1.283), factor 2 M = 3.19(SD = 1.108), and factor 3 M = 1.809(SD = 0.444).

Conclusion

Our instrument is adequate to measure social determinants of health in persons with neurodegenerative dementia with the input of caregivers.
Associations of sensory impairments with cognition vary by race in older US adults
Authors: Arshad Faaizah , Pinto Jayant M , Yaffe Kristine , Brenowitz Willa D
Published: June 2023

Background

Sensory impairments are associated with increased dementia risk in older adults, but whether such associations vary by race is unknown.

Method

We studied 2,058 participants from the National Social Life, Health, and Aging Project (NSHAP) aged 57 to 85 without cognitive impairment at the time of recruitment. 8% identified as Hispanic, 13% as non‐Hispanic Black, and 76% as non‐Hispanic White. Sensory function in the 5 senses (vision, hearing, smell, taste, touch) was measured by visual acuity, interviewer‐rated hearing, a five‐item smell identification test, a four‐item taste identification test, and touch by single point and 2‐point discrimination. Previously published cut‐points defined poor, fair, and good levels of function. Cognition was measured with a modified version of the Montreal Cognitive Assessment (MoCA) in the same subjects 10 years later. Linear regression models with interaction terms evaluated whether the association between sensory impairments and cognition differed by race/Ethnicity, adjusting for age, sex, and education.

Result

64.7% of individuals had poor sensory function (≥1 impairment). Hispanic (n = 228) and non‐Hispanic Black (n = 237) older adults were more likely to have ≥1 sensory impairments and to have lower cognition scores compared to non‐Hispanic Whites (n = 1,593). In adjusted models including all participants, fair interviewer‐rated hearing (‐0.68 points, CI:‐1.09,‐0.27), fair smell (‐0.77 points, CI:‐1.14,‐0.41), fair taste (‐0.37 points, CI:‐0.73, ‐0.01), and having multiple sensory impairments (‐0.73 points, CI:‐1.27, ‐0.19) were associated with lower cognition compared to good sensory function/ no impairments. For smell, taste, and touch there were differences by race. The estimated effect of fair smell on subsequent lower cognition was stronger in non‐Hispanic Blacks compared to Whites (‐0.99 points, CI: ‐1.90,‐0.09, p for interaction = 0.03). The estimated effect of poor taste on worse cognition was stronger in non‐Hispanic Whites compared to Hispanics (‐1.42 points, CI: ‐2.62,‐0.22, p for interaction = 0.02). There was a significant association between poor touch and lower cognition in Hispanics but not for other racial groups (‐2.03 points, CI: ‐3.81, ‐0.25, p = 0.03).

Conclusion

We found important racial differences in how sensory dysfunction predicts future cognition. Sensory impairments are often modifiable; further insight on these differences may help stimulate efforts to reduce disparities in dementia burden.
Higher depression scores in cognitively unimpaired individuals affect event‐related potentials similar to those of MCI
Authors: Öz Didem
Published: June 2023

Background

Depression is common among seniors, both cognitively unimpaired (CU) and in individuals with Mild Cognitive Impairment (MCI). Electroencephalography (EEG) event‐related Potentials‐P300 is one of the most commonly used electrophysiological parameter associated with cognition. This study aimed to investigate P300 mean amplitude differences between CU individuals and those with MCI, with and without depressive symptoms.

Method

The study included 20 CU individuals with depression [CU‐Dep(+)], 21 MCI patients [MCI‐Dep(+)] with depression, 20 CU individuals without depression [CU‐Dep(‐)] and 22 MCI patients [CU‐Dep(‐)] without depression. Geriatric Depression Scale (GDS) ≥14, was the cut‐off score for classification of Dep (+) or Dep (‐). CU seniors had no significant neurological abnormality or global cognitive impairment. Participants with MCI had cognitive impairment as defined with performances ≥1.5 standard deviations below for age‐and education‐matched controls and with no impairment of daily‐living activities. The ERPs were recorded with a visual classical oddball paradigm, mean P300 amplitudes were measured in the 250‐550ms time window.

Result

The repeated‐measures ANCOVA showed no effect of age and education on P300 but a LOCATION x GROUP interaction [F(6,158) = 2.56,p = 0.035) and main GROUP effect [F(3,79) = 2.56,p = 0.003). Post‐hoc analysis revealed CU‐Dep(‐) had higher P300 amplitudes than MCI‐Dep(+). Moreover, CU‐Dep(+) had lower P300 amplitudes than CU‐Dep(‐) in frontal electrode location. Although there were no significant results, there were a gradual decline trend from CU‐Dep(‐) to MCI‐Dep(+)(Figure 1., Table 2.).

Conclusion

The current study showed reduced P300 amplitudes in CU and MCI groups with depression as compared to those without depression. The P300 potential may be a useful tool to determine possible changes or impairments due to sub‐threshold depressive symptoms. However, the lack of significant difference between CU‐Dep(‐) and MCI‐Dep(‐) shows us that the P300 amplitude difference may not always be associated with cognitive status, but may also be associated with depressive symptoms. Thus, it is necessary to consider the depressive symptoms of the participants in cognitive EEG studies.
Examining the factors that moderate progression from subjective cognitive decline to objective cognitive decline: A 4‐year longitudinal study
Authors: Katayama Osamu , Lee Sangyoon , Bae Seongryu , Makino Keitaro , Chiba Ippei , Harada Kenji , Morikawa Masanori , Tomida Kouki , Shimada Hiroyuki
Published: June 2023

Background

Subjective cognitive decline (SCD) in older adults has been identified as a risk factor for dementia, although the literature is inconsistent, and the factors that contribute to this inconsistency are not fully understood. We focused on the protective factors for dementia risk and aimed to determine whether SCD has more protective factors for dementia risk and whether they reduce the association with future objective cognitive decline (OCD) from a 4‐year longitudinal study.

Method

We included 4,363 older adults (age: 71.7±5.3 [mean ± standard deviation] years; 2,239 women) from the National Center for Geriatrics and Gerontology–Study of Geriatric Syndromes. SCD, OCD, and protective factors such as lifestyle and activity for dementia risk were assessed using a face‐to‐face interviews and objective cognitive assessment tools. Participants were categorized into cognitive status: normal cognition (neither SCD nor OCD), SCD only, OCD only, and SCD and OCD (both SCD and OCD) groups. Four years later, participants were classified as having or not having mild cognitive impairment or global cognitive impairment. Binomial logistic regression analysis was performed with follow‐up on the cognitive status and at the baseline cognitive status groups as the dependent and independent variables, respectively.

Result

Potential confounding factors‐adjusted odds ratios for SCD only, OCD only, and SCD and OCD groups for developing OCD at follow‐up were 1.08 (95% CI, 0.80‐1.45; p = 0.608), 4.00 (95% CI, 2.64‐6.07; p<0.001), and 3.12 (95% CI, 2.22‐4.37; p<0.001), respectively. The SCD only group had more protective factors for dementia risk than the OCD only group.

Conclusion

Community‐dwelling elderlies with SCD had more protective factors for dementia risk at the baseline and a lower association with OCD in the 4‐year follow‐up. Our results suggest that the presence of protective factors for dementia risk may be a contributing factor to the inconsistent literature on the SCD outcomes.