bluuebunny/crossref_metadata_2025 huggingface dataset:
Wireless Dosage Monitoring for Donepezil Transdermal Patches as a Novel Concept
Authors: Bendas Ehab R
Published: December 2023

Remote therapy, also known as teletherapy or online therapy, refers to the provision of mental health services through electronic means, such as phone, text, or video conferencing. With the advent of the internet and other digital technologies, it has become increasingly possible for therapists and patients to interact remotely, without the need for in‐person visits.

Remote therapy has gained popularity in recent years, particularly during the COVID‐19 pandemic, as it allows individuals to access mental health support from the safety and convenience of their own homes. It is also a useful option for those who live in rural or underserved areas, where access to in‐person therapy may be limited.Donepezil (cholinesterase inhibitor) is effective for improving the cognitive and global functioning of patients with Alzheimer’s disease. This drug was formulated as transdermal patch by the ethanol based nano carrier & micro gas sensor. Our work intends to create a simple approach to administer Donepezil systemically by applying a transdermal patch, as well as a practical monitoring technique by employing a gas sensor that collects data and wirelessly transmits it to cell phone application. The application depends on short massage services. Wireless technology offers several advantages, including improved data mobility and data transfer via various methods such as Wi‐Fi, internet connection, or Bluetooth to enable continuous medical monitoring. The sensor has the advantages of being small, not battery operated and delivering doses without human interference that reduces error, making the technique favorable for elderly and mentally disabled patients. This innovative technology permits the physician to monitor the drug level in the patch and give an alarm for applying the next doses through cell phone application.

In conclusion, remote therapy using the transdermal route of administration is a valuable option for individuals suffering from cognitive disease like Alzheimer’s Disease because it avoids first‐pass effects, reduces adverse symptoms associated with the oral route, and increases the economic benefits of using the correct doses when needed.
Prognostic value of Neurofilament light chain, [18F]‐PI2620 PET and [18F]GE‐180‐PET in amyloid‐negative Corticobasal Syndrome
Authors: Palleis Carla , Franzmeier Nicolai , Weidinger Endy , Bernhardt Alexander , Katzdobler Sabrina , Finze Anika , Nuscher Brigitte , Rauchmann Boris‐Stephan , Perneczky Robert , Haass Christian , Brendel Matthias , Levin Johannes , Höglinger Günter
Published: December 2023

Background

Corticobasal syndrome (CBS) with underlying 4‐repeat tauopathy is a progressive neurodegenerative disorder characterized by declining cognitive and motor functions. Biomarkers for assessing pathological brain changes in CBS including tau‐ and microglia‐PET or neurofilament light chain (NfL) have recently been evaluated for differential diagnosis and disease staging, yet the prognostic accuracy of these biomarkers for predicting disease trajectories remains unclear. To address this, we performed a head‐to‐head comparison of neuroimaging (tau‐PET, microglia‐PET) and plasma biomarker NfL as prognostic tools for future clinical trajectories in 21 CBS patients with longitudinal clinical data.

Method

We included 21 clinically diagnosed CBS patients with ∼2‐year clinical follow‐up data who underwent baseline [18F]PI‐2620‐PET for assessing tau pathology, [18F]GE‐180‐PET for microglia activation and plasma‐NfL for neurodegeneration. All patients were negative on amyloid biomarkers. To quantify tau and microglia load we assessed summary scores of whole‐brain, cortical and subcortical tracer signal. NfL was assessed using immunoassays on the Simoa platform. Symptom progression was determined using a battery of cognitive and motor tests. Using linear mixed models, we tested whether the assessed biomarkers at baseline were associated with faster progression of symptoms over time (i.e. time x biomarker interaction).

Result

Overall, there was on average a rapid decline over time on the assessed clinical scores. For tau‐PET, CBS patients with higher global tau load showed faster clinical progression. This time x tau‐PET interaction was driven by cortical rather than subcortical tau‐PET load. Patients with higher [18F]GE‐180‐PET whole‐brain load showed slower clinical progression. Concerning plasma biomarker NfL, higher plasma‐NfL was prognostic of faster clinical deterioration. In a subsequent sensitivity analysis, we found that tau‐PET, microglia‐PET as well as plasma‐NfL showed significant (i.e. p<0.05) interaction effects with time on clinical trajectories when tested in the same model, suggesting that these biomarkers explain unique variability in future disease trajectories.

Conclusion

[18F]PI‐2620 tau‐PET, [18F]GE‐180 microglia‐PET and plasma‐NfL show prognostic potential for clinical progression in CBS patients with probable 4‐repeat tauopathy, which can be useful for clinical decision making as well as stratifying patients in clinical trials.
Spectrum of Neuropsychiatric Symptoms in Southeast Asians with Prodromal Dementia
Authors: Leow Yi Jin , Soo See Ann , Kumar Dilip , Vipin Ashwati , Zailan Fatin Zahra , Sandhu Gurveen Kaur , Lee Faith Phemie Hui En , Ghildiyal Smriti , Chen James Xiao Yuan , Dang Chao , Ng Kok Pin , Kandiah Nagaendran
Published: December 2023

Background

Behavioral and psychological symptoms are one of the earliest observable changes when a person experiences cognitive decline. These symptoms are common and are known as Neuropsychiatric symptoms(NPS), which increases risk of progression to dementia. The prevalence of NPS was compared in a cohort of Southeast Asian adults with Subjective Cognitive Decline(SCD) and Mild Cognitive Impairment(MCI).

Method

This study utilized cross‐sectional data from the Biomarkers and Cognition Study, Singapore(BIOCIS). From February to December 2022, participants who met criteria for SCD and MCI in accordance with NIA‐AA’s criteria were classified into two groups, NPS and without‐NPS, based on clinical cut‐offs of Depression Anxiety Stress Scales(DASS) scores. Self‐reported questionnaires assessed behavioral symptoms ‐ Mild Behavioral Impairment‐Checklist(MBI‐C); Dementia‐Quality of Life Instrument(Dem‐QOL); International Physical Activity Questionnaire(IPAQ); and Pittsburgh Sleep Quality Index(PSQI). Group comparisons of data were applied separately using univariate analyses. A Receiver Operating Characteristic analysis was conducted to test the diagnostic performance of MBI‐C total, MBI‐C‐subdomains, and PSQI in distinguishing participants with NPS and without‐NPS.

Result

488 participants (μ age = 62.7±9.64,42.2% males) were analyzed. 133(27.25%) reported significant NPS symptoms. Participants with NPS reported significantly more symptoms on MBI‐C‐total(p<.001); interest(p<.001); mood(p<.001); control(p<.001), social(p<.001), and beliefs(p<.001) subdomains; poorer sleep(p<.001) and lower quality of life(p<.001) compared to participants without‐NPS(Table 1). MBI‐C‐total, MBI‐C‐mood and MBI‐C‐control subdomains were effective in discriminating between participants with and without NPS, with an acceptable Area Under the Curve: .782(.732‐.833) for MBI‐C‐total, .753(.699‐.807) for MBI‐C‐mood, and .753(.699‐.807) for MBI‐C‐control(Figure 1 and Table 2).

Conclusion

In a prodromal cohort of southeast Asians, participants with NPS reported significantly worse scores on MBI‐C‐total and subdomains, specifically ‐ decreased motivation, emotional dysregulation, impulse control, social inappropriateness, abnormal perceptions, as well as poorer sleep quality and a lower quality of life compared to participants without‐NPS. The results are keeping with the strong evidence that behavioral changes are among the first symptoms noticeable to the person themselves as they begin to experience cognitive decline. The self‐reported questionnaires used are easily administered and brief, which has important real‐world relevance for early diagnoses of, and timely intervention for prodromal dementia. Further studies of BIOCIS is on‐going to investigate the impact of NPS on cognitive decline.
Diagnostic performance RT‐QuIC based detection of alpha‐synuclein seeds in a clinical cohort with cognitive impairment
Authors: Esteller Diana , Guillén Núria , Sarto Jordi , Ramos‐Campoy Oscar , Falgàs Martínez Neus , Molina Laura , Borrego‐Écija Sergi , Ruiz‐García Raquel , Naranjo Laura , Antonell Anna , Lladó Albert , Sanchez‐Valle Raquel , Balasa Mircea
Published: December 2023

Background

Lewy Body Dementia (LBD) is the second most common neurodegenerative dementia. To date, no validated biochemical marker is available to support clinical diagnosis. The development of the Real‐Time Quaking‐Induced Conversion (RT‐QuIC) assay for detecting alpha‐synuclein (aSyn) seeds in biological samples can be a sensitive biomarker specific for the diagnosis easily applicable in a clinical setting. We aimed to describe the diagnostic performance of RT‐QuIC aSyn assay in cerebrospinal fluid (CSF) to diagnose LBD in a clinical cohort with cognitive impairment.

Method

A cohort of subjects with cognitive impairment (neurodegenerative and non‐neurodegenerative) with available CSF sample at the moment of first evaluation was selected by convenience sample in our database. Subjects had clinical follow‐ups ranging from 6 months to 12 years and current clinical diagnosis according to established consensus criteria. The diagnostic performance of RT‐QuIC aSyn for the diagnosis of LBD were evaluated.

Result

The test was evaluated in 155 subjects (age 65 years (SD 11), MMSE 24 (SD 4.5), 56% male) with the following clinical diagnoses: LBD (n = 40), Alzheimer’s disease (AD) (n = 73)(all with compatible CSF profile), frontotemporal dementia (FTD) (n = 7), non‐neurodegenerative mild cognitive impairment (MCI) (n = 21), other neurodegenerative diagnoses (n = 12) and healthy controls (n = 2). aSyn was detected in 33/40 (83%) LBD patients, 7/73 (10%) AD, 0/7 FTD patients, 0/21 MCI patients, 0/12 patients with other neurodegenerative diseases and 0/2 healthy controls.

Only 3/7 (42%) LBD subjects with a negative RT‐QuIC asyn fulfilled criteria for LBD (established or prodromal) at the moment of first evaluation as compared with 23/33 (69%) of LBD with positive RTQuIC suggesting a more initial disease in the negative group at the moment of CSF sampling.

The sensitivity and specificity of the assay were 83% and 94% respectively for the diagnosis of LBD, with a PPV of 83% and a NPV of 94%.

Conclusion

Detection of αSyn seeds by RT‐QuIC has a good performance in identifying patients with LBD in a clinical cohort of cognitively impaired subjects. The test also identifies aSyn co‐pathology in a subgroup of subjects diagnosed with AD.
Cognitive functions in patients with Human Immunodeficiency virus. Infection in Nigeria: assessment using computer assisted neuropsychological test batteryhi7
Authors: Sunmonu Taofiki Ajao , Ogunrin Olubunmi Akindele , Komolafe Morenikeji Adeyoyin , Imarrhiagbe Frank I
Published: December 2023

Background

There is paucity of information on the cognitive functions in patients with HiV infection in Nigeria

Method

Fifty patients with HIV infection were studied along age,sex and level of education matched 50 HIV negative controls subjects.The patients underwent general physical and neurologically examinations. Laboratory investigations such as blood glucose test, CD4 cell counts, Full blood counts,CXrays, HIV clinical staging were done for all patients Fepsy neuropsychological Test battery was used for cognitive asssessment in all the study participants.

Result

The patients with HIV infections performed worse on measures of psychomotor speed (auditory reaction times, visual reaction times, attention concentration(Binary choice reaction times and computerized visual searching tasks) than the controls The prevalence of sevvere cognitive infection in HIV patients was 20%.Presence of anaemia and advanced HIV disease stage were predictive of cognitive impairment in the patients with HIV infection.

Conclusion

HIV Associated Cognitive Disorder is common in patients with HIV in this study
Understanding the molecular mechanisms of TDP‐43 neurotoxicity in ALS and FTD to inspire targeted therapies
Authors: Polymenidou Magdalini , Wiersma Vera I
Published: December 2023

ALS and FTD are fatal and incurable neurodegenerative diseases, characterized by accumulation of pathologic forms of RNA‐binding proteins, predominantly TDP‐43. The functional consequences and potential neurotoxic effects of the highly heterogeneous TDP‐43 aggregates observed in postmortem brains are debated. Combining structural protein analysis with cellular systems we uncovered a novel and unexpected mechanism that counteracts pathologic aggregation of TDP‐43. More recently, we described two distinct mechanisms of aggregation resulting in either nuclear of cytoplasmic TDP‐43 aggregates, resembling the neuropathological heterogeneity described in FTD patients and potentially unravels the origins of heterogeneous pathological species occurring in TDP‐43 proteinopathies. We also showed that FTD heterogeneity is associated with alternate pathological TDP‐43 conformations, reminiscent of prion strains. We used advanced microscopy techniques to explore the differences in the physical and seeding properties between these pathological TDP‐43 aggregates. We found that the subcellular environment and organization of TDP‐43 aggregates differs in patient brains in a subtype‐specific manner. When isolated and introduced in cells, these distinct TDP‐43 assemblies triggered neoaggregate formation with seeding potencies and morphologies that mimicked human brain pathology. To study neurodegeneration phenotypes in human neurons, we developed a new methodology for generating human neuronal networks with remarkable maturity, longevity and reproducibility. Combining high density multielectron arrays and single cell RNA sequencing, we demonstrated the potential of these cultures for modeling neurodegeneration. In this new model, we identified novel RNA targets of TDP‐43, which we found abnormally accumulated in neurons with TDP‐43 pathology in human brains of ALS and FTD patients. The implications of these studies for understanding the mechanisms of neurodegeneration and inspiring therapeutic approaches will be discussed.
Overview on epidemiology and neuropathologic staging of limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic changes (LATE‐NC)
Authors: Nelson Peter T
Published: December 2023

Background

Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is increasingly appreciated to have a very large impact on public health. The goal of this presentation is to provide an overview about what is known about the epidemiology of LATE, and also to describe some recent changes to the criteria for the diagnostic classification of LATE neuropathologic change (LATE‐NC). The prevalence of LATE‐NC and Alzheimer’s disease neuropathologic changes (ADNC) are each challenging to assess definitively, due to the requirement of state‐of‐the‐art autopsy verification across human populations.

Method

A set of neuropathologic and clinical data were compiled from 13 high quality community‐ and population‐based longitudinal studies. The total number of participants included was 6,196, and the average age of death was 88.1 years. This study provided a credible estimate of the current prevalence of LATE‐NC in advanced age, with or without comorbid ADNC. Diagnostic classification also must take into account neuropathologic heterogeneity.

Result

LATE‐NC was seen in almost 40% of participants and in ∼25% of those lacking ADNC. A total of 3,267 of these participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP‐43 inclusions (FTLD‐TDP). Another focus of the talk is recent research findings that have enabled increasingly precise guidance on how to differentiate LATE‐NC from other subtypes of TDP‐43 pathology (e.g., FTLD‐TDP and amyotrophic lateral sclerosis [ALS]), and how to render diagnoses in unusual situations in which TDP‐43 pathology does not match the staging scheme proposed in 2019. Specific recommendations are made about when to avoid the diagnostic term of LATE‐NC, based on current knowledge. Neuroanatomical regions of interest in LATE‐NC are specified factoring in neuropathologic data from different research centers.

Conclusion

LATE‐NC is a very common dementia, differentiable from ADNC or FTLD, and recent studies have refined our ability to make the diagnosis of LATE‐NC with increasing specificity. Areas needing additional study will be highlighted.
Discovery and optimization of the first‐in‐class TDP‐43 PET tracer
Authors: Seredenina Tamara , Vokali Efthymia , Dreyfus Nicolas , Chevallier Elodie , Afroz Tariq , Jaquier Thomas , Serra Andreia Monica , Clavel Mathieu , Rathnam Monisha , Melly Tania , Kroth Heiko , Pfeifer Andrea , Kosco‐Vilbois Marie
Published: December 2023

Background

Intracellular aggregation of TDP‐43 is found in most patients with amyotrophic lateral sclerosis (ALS), 45% of patients with frontotemporal dementia (FTD) and 30‐50% of patients with clinical diagnosis of Alzheimer’s disease. Sensitive fluid or imaging biomarkers of TDP‐43 pathology are currently not available. Direct detection of TDP‐43 aggregates by positron emission tomography (PET) holds promise for a more accurate diagnosis, patient stratification and assessment of therapeutic efficacy in clinical trials.

Methods

Using ACI’s Morphomer® small molecule library focused on brain penetrant and beta sheet binding compounds, initial hits were identified, and iterative medicinal chemistry applied to discover compounds with optimized properties. Radiobinding and autoradiography experiments on FTLD‐TDP brain samples were used to evaluate affinity and target engagement. These techniques were also used to assess selectivity over other aggregation‐prone proteins using brain material from Alzheimer’s (AD) and Parkinson’s disease (PD) cases. Brain pharmacokinetic (PK) profile was obtained in mice, followed by assessment of brain uptake, distribution and washout for selected 18F radiolabeled compounds in non‐human primates (NHP).

Results

Several chemical series showing nanomolar binding affinity to aggregated TDP‐43 from patient brain samples were identified. The specificity of binding was further confirmed by high resolution autoradiography enabling visualization of target engagement on TDP‐43 inclusions in FTLD‐TDP brain sections. In addition, the most advanced compounds differentiated FTLD‐TDP from control by classical autoradiography on patient brain sections. Selectivity over amyloid beta, alpha‐synuclein and Tau was observed. The compounds with the most favorable brain penetrantion properties demonstrated fast and substantial brain uptake and fast and complete washout in NHPs.

Conclusions

First‐in‐class TDP‐43 PET ligands have been discovered with the potential to identify FTLD‐TDP pathology by PET. These tools may finally allow the ability to detect and follow the progression of TDP‐43 pathology in the brains of living patients with certain TDP‐43 proteinopathies.
Measuring the volume of Thalamic nuclei in cognitively unimpaired, middle‐aged individuals from the PREVENT‐Dementia cohort
Authors: Shah Sita , Dounavi Maria‐Eleni , Malhotra Paresh A , Lawlor Brian A , Naci Lorina , Koychev Ivan , Ritchie Craig W , O'Brien John T
Published: December 2023

Background

The thalamus consists of multiple nuclei involved in processes such as sleep and cognition. Individuals with AD, mild cognitive impairment (MCI) and asymptomatic individuals with risk factors for early‐onset AD display a reduction in thalamic volumes (Lee et al., 2013; Zidan et al., 2019). The pulvinar, anteroventral, centromedian and mediodorsal nuclei are amongst the thalamic nuclei affected in AD and MCI (Bernstein et al., 2021). Our aim was to investigate thalamic nuclei volumes and their association with cognitive performance in middle‐aged, cognitively unimpaired individuals with respect to dementia family history (FHD).

Method

701 participants were recruited into the PREVENT‐Dementia study. 645 T1‐weighted 3T MRI scans underwent thalamic segmentation using Freesurfer 7.1.0. The 24 sub‐nuclei were grouped into 6 regions (Table 1); 1) Anterior, 2) Lateral, 3) Ventral, 4) Intralaminar, 5) Medial and 6) Posterior (Iglesias et al., 2018). Cognitive performance was evaluated using the COGNITO battery.

Differences in volumes with respect to parental FHD and the effect on cognitive performance was analysed using robust linear regression, with age, sex, years of education and total intracranial volume as covariates and FDR correction for multiple comparisons.

Result

Individuals with a FHD had significantly smaller volumes of the medial thalamus (pFDR = 0.037), particularly the mediodorsal medial (MDm, p = 0.016) and lateral (MDl, p = 0.016) nuclei (Figure 1).

Individuals with a FHD performed significantly better on the delayed (p = 0.015) and descriptive recall (p = 0.03) tests. Larger volumes of the MDm (p = 0.003) and MDl (p = 0.036) were associated with a faster processing speed in those without FHD. Larger volumes of the MDl were also associated with greater recall in narrative and descriptive recall tests (p = 0.007 and p = 0.025, respectively) in those without FHD (Figure 2).

Conclusion

Individuals without FHD have larger volumes of the MDm and MDl nuclei, which appear to exert a protective effect on cognitive performance, whilst having little effect in those with FHD. This could represent initial dysregulation in the disease process, which could be further evaluated with functional imaging or longitudinal follow up to assess for cognitive decline.
Prosody variations to improve cognitive processing in Alzheimer’s patients
Authors: Rodero Emma , Rodríguez‐de‐Dios Isabel , Larrea Olatz , Mas Lluis
Published: December 2023

Background

Alzheimer’s disease (AD) is one of the most widespread diseases in our society. Social interaction and communication with caregivers represent a challenge (Lowery, 2013). Few studies have taken a communication perspective on this problem. These studies show the importance of a satisfactory communicative exchange to improve the relationship between caregivers and Alzheimer patients (AP) (McGilton et al., 2017;Small et al., 2009). However, the variable prosody has yet to be deeply explored, yet it may be highly relevant to the quality of communication (Small et al., 2009). The main objective of this project was to analyze what prosody strategies improve communication between AP and their caregivers.

Method

An experiment was designed with a corpus of informative instructions related to AP’s routines. Different audio versions were produced with prosody variations: pitch (high or low), intensity (high or low), speed (fast and slow), intonation (monotonous, soft, or marked), emphasis/stress (soft or marked), and attitude (paternalistic style or loving style). The experiment was conducted with two groups of participants over 65 years old (77 on average): the experimental group, 30 subjects in a soft state AD, and the control group, 30 subjects without AD. The dependent variables (likeability, comprehension) were evaluated with yes/no (green/red buttons) questions after listening to the voice instruction with different prosody variations. Recognition was assessed with a specific test.

Result

Results showed that the most effective strategies were the intonation variations (soft or marked), the use of emphasis (soft or strong), the loving style when talking, the middle pitch, and the paused or slow speed. The least effective ones were speaking with high intensity (volume), fast speech rate, paternalistic style, and monotonous intonation

Conclusion

In light of the findings, the prosody variations strategies can significantly improve the communication exchanges between AP and their family members and/or caregivers.
The Bidirectional Association of TBI and Dementia/MCI among older US Veterans
Authors: Yaffe Kristine , Gardner Raquel C. , Peltz Carrie , Bahorik Amber L , Xia Feng , Albrecht Jennifer S
Published: December 2023

Background

Prior studies have reported a link between traumatic brain injury (TBI) and risk of adverse neuropsychiatric outcomes including dementia. However it is unclear how prevalent these conditions are prior to TBI and if they are predisposing factors in addition to sequalae.

Methods

We studied older (age >55 years) US veterans who were followed for care at Veterans Affairs Medical Centers across the nation from 2000 to 2019. We first identified all veterans with an incident TBI diagnoses defined as no prior TBI diagnosis, having been seen in an emergency department (ED), having a brain imaging scan (primarily CT) within one day of ED visit and with a subsequent new TBI diagnosis in the electronic medical record (EMR). We then determined 2‐year age‐adjusted prevalence rates (rate per 1000 person‐years and 95% confidence interval or CI) for dementia and mild cognitive impairment (MCI) prior to and post incident TBI. We also compared prior TBI prevalence to prevalence among 1:3 matched (on age and index date) veterans without TBI.

Results

There were 13,709 primarily male veterans with incident TBI with mean age of 77.7 sd 9.1 years, 81% were non‐Hispanic White. Compared to the 41,127 veterans without TBI (mean age = 77.9, sd 9.1), veterans prior to having an incident TBI had almost a six‐fold greater pre‐TBI age‐adjusted prevalence of dementia (104.9; 95% CI 100.8‐109.0 vs 18.6; 95% CI 17.6‐19.7, p<0.001) and MCI (48.0; 95% CI 45.2‐50.7 vs 8.1; 95% CI 7.4‐8.8, p<0.001). After the incident TBI diagnosis, the age‐adjusted prevalence rates were even higher: dementia (193.5; 95% CI 187.7‐199.2) and MCI (59.3; 95% CI 56.0‐62.6).

Conclusions

Among older US veterans, there is a bidirectional association with dementia/ MCI and TBI with very high prevalence prior to TBI (compared to those without TBI) and even greater prevalence after TBI. These findings highlight the importance of prevention strategies for both pre‐ and post‐TBI cognitive impairment.
Impact of Dementia on Days at Home after Traumatic Brain Injury among Older Medicare Beneficiaries
Authors: Albrecht Jennifer S
Published: December 2023

Background

Traumatic brain injury (TBI) is a highly disabling event among older adults, contributing to disability in activities of daily living and elevated risk for nursing home admission. Older adults with Alzheimer’s disease and related dementias (ADRD) are more susceptible to TBI given increased fall incidence in this population, but how ADRD influences long‐term disability outcomes after TBI has been challenging to ascertain because of small sample sizes in prior work. Home time, a claims‐based measure of time spent at home and not hospitalized following a health‐related event, may aid in determining the association of ADRD and post‐TBI outcomes among older adults. Thus, the objective of this study was to examine the impact of TBI on home time among older adults with ADRD.

Methods

We conducted a retrospective cohort study using a random sample of Medicare administrative claims data for years 2010‐2018. Community‐dwelling Medicare beneficiaries aged ≥65 years hospitalized with a primary diagnosis of TBI were included and ADRD was defined at baseline (i.e. before TBI) using diagnostic codes. Home time was calculated by subtracting the number of days spent in a care environment or deceased from the total follow‐up available for each of the twelve follow‐up months post‐TBI. We modelled monthly days at home as a function of ADRD and covariates using generalized estimating equations.

Results

There were 20,350 participants in the study, of whom 6,683 (33.8%) had a pre‐existing diagnosis of ADRD. In regression models that accounted for pre‐TBI days at home, demographic and clinical characteristics, and probability of survival, beneficiaries with ADRD spent fewer days at home following TBI compared to beneficiaries without ADRD (rate ratio 0.90; 95% confidence interval 0.89, 0.92). This disparity was equivalent to almost 50 fewer days spent at home over the year following TBI.

Conclusion

TBI resulted in a significant loss of home time over the year following injury, a loss markedly worse among older adults with ADRD.
Functional connectivity changes of the Locus Coeruleus in Alzheimer’s Disease
Authors: Hou Ruihua , Ali Mobeen , Brown Matthew
Published: December 2023

Background

Growing evidence indicates neurone loss in the Locus Coeruleus(LC) in patients with Alzheimer’s Disease(AD). The widespread projection and rich connectivity of the LC with multiple brain regions and its interaction with different neural networks suggests the importance of investigating the functional connectivity of the LC, an area of research which has been less studied.

Aims

The primary aim of this study was to test for differences in functional connectivity of the LC between AD subjects and matched controls using neuromelanin‐sensitive MRI(NM‐MRI). The secondary aim of this study was to test for the effects of AD on the resting state networks.

Methods

Pre‐processing of the fMRI and structural MRI data from 23 AD subjects and 23 controls was completed using the FMRIB Software Library(FSL). The images were skull‐stripped, registered, and normalised to the MNI152_t1_2mm_brain template. LC masks were created from the NM‐MRI scans also using FSL. The subsequent data was processed using the CONN toolbox. Seed‐to‐voxel and ROI‐ROI analysis were used to produce connectivity maps and comparisons were conducted between AD and controls, left and right LC, mild and moderate AD, and resting state networks.

Results

AD subjects had connections from the LC to only 43 brain regions, compared to 80 brain regions in the controls. In comparison to controls, AD subjects had reduced LC connectivity in the subcallosal cortex(p‐FDR = 0.016417), increased LC connectivity in the right supramarginal and postcentral gyri(p‐FDR = 0.000002), and reduced connectivity in the default mode network(p‐FDR = 0.000286) and sensorimotor network(p‐FDR = 0.027524). The left LC in the AD subjects had significant connections to only 56 brain regions compared to 81 brain regions in the right LC. In particular, the left LC had decreased number of significant connections to the amygdala and vermis, compared to the right LC. The number of significant LC connections decreased with progression from controls to mild AD to moderate AD.

Conclusions

This study provides new evidence of reduced LC functional connectivity in AD patients and asymmetrical reduction in the LC skewed towards the left LC. LC connectivity reduction could indicate pathogenesis and progression of AD, aiding prediction of disease progression and development of novel intervention targets.
Status report on palliative care in Alzhiermers patients : Dark reality in resource poor nations
Authors: Rohan S P , Patil Y , Verma N
Published: December 2023

Background

Social stigma, Fatigue, sexual dysfunction, Sleeplessness, depression commonly seen in Alzhiermers patients . Palliative inaccessible in rural/tribal areas. Hence our NGO nurses took initiatives to help alleviate suffering of women with Alzhiermers patients since October 2018.

Method

We surveyed 110 subjects through QOL‐questionnaires. After 22 weeks therapy with psychosocial support. Counseling & palliative care with anti‐depressants/pain‐killers/nutrition, QOL improved to statistically significant level. Requirement of palliative care evaluated by Palliative Care Problem Severity Scale (PCPSS). Traditional faith‐healers involved for more psychological impact on patients community. Community leaders involved to reduce social stigma/discrimination among community.

n = 110. Of these statistically over 90% express sexual‐dysfunction, 68% experience loneliness; 70% suffer social neglect/humiliation, 64% had depression. Importance of spirituality/religion in coping with terminal‐illness is increasingly recognized Hence Our NGO‐nurses involved community‐leaders to make more women involved in our spiritual healing.

Result

currently 210 specialist palliative care beds required for our Rural/tribal population of 16,00,000. But only 80 available. 60% expressed that religious/community support/faith was most important factor that helped them to cope with Alzhiermers. higher scores of QOL (ANOVA p < 0.001) correlated with lack of sexual dysfunction/pain. Our NGO‐initiative suggests that over 70% patients will need well trained specialist for home‐based‐care.

Conclusion

Life‐span/QOL of Alzhiermers patients‐sufferers depends on social acceptance & appropriate‐palliative‐care. NGO‐personals should be trained in Palliative‐care‐services. Field of Spiritual/psycho‐social/community support is fertile ground for further investigations. We need focused platform like AAIC to discuss our project ideas/concerns/difficulties with senior researchers.
Structural Correlates of Speech Biomarkers in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Bae Minju , Ham Hyunsun , Lee Dasom , Kim Keun You , Lee Jun‐Young
Published: December 2023

Background

In the present study, we aimed to confirm the association between speech characteristics of individuals with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI) and brain regions, and to investigate the neurobiological basis of speech‐based AD detection.

Method

Individuals with MCI (n = 13, age = 78.3), mild‐to‐moderate AD (n = 12, age = 77.8) underwent a structural MRI scan and engaged in three speech tasks: an interview, sentence repetition, and paragraph recall. From the speech samples, we extracted frequency‐related, intensity‐related, and temporal features which were found to be altered in the course of AD and MCI pathology. We selected nine regions of interest (ROI) which were found to be involved in speech production and reduced in MCI and AD pathology; the Inferior Frontal Gyrus (IFG), the Medial Frontal Gyrus (MFG), the Precuneus, the Inferior Parietal Lobe (IPL), Inferior Temporal Gyrus (ITG), Medial Temporal Gyrus (MTG), the Superior Temporal Gyrus (STG), the Fusiform Gyrus (FFG), and the Cerebellum. The linear mixed‐effect analysis was used to identify the associations between speech features and regional brain volumes.

Result

The Left IPL (χ2 (1) = 7.69, corrected P = 0.033), the Right ITG (χ2 (1) = 11.5, corrected P = 0.0128) the Right FFG (χ2 (1) = 9.35, corrected P = 0.0198) reduced the pitch of voice by about 0.887 ± 0.292, 1.368 ± 0.329, and 1.69 ± 0.429 respectively. The associations between the Right FFG (χ2 (1) = 4.58, corrected P = 0.0900), Left FFG (χ2 (1) = 5.87, corrected P = 0.0675) and loudness were marginally significant, with the reduction of volumes in the Right FFG and Left FFG decreasing the loudness by 0.096 ± 0.041, and 0.1165 ± 0.0454. The marginally significant associations were observed between the Right IPL (χ2 (1) = 4.75, corrected P = 0.0900), the Left FFG (χ2 (1) = 0.39, corrected P = 0.53) and the speech rate, and the atrophy of brain regions decreased the speech rate by 0.0824 ± 0.0363, 0.0535 ± 0.0079.

Conclusion

The present study identified the associations between speech biomarkers and regional brain volumes providing clinical validity for the speech‐based Alzheimer’s disease detection.
The nebulous association between cognitive impairment and falls in older adults : a systematic review of the literature
Authors: Leroy Victoire , Martinet Valérie , Nunkessore Oumashankar , Dentel Christel , Durand Hélène , Mockler David , PUISIEUX François , Fougere Bertrand , Chen Yaohua Sophie
Published: December 2023

Background

In older people, dementia is a well‐established risk factor for falls. However, the association and the causal relationship between falls and earlier stage of cognitive impairment remains unclear. The purpose of the study was to review the literature data on the association between falls and cognitive impairment, no dementia, including Mild Cognitive Impairment.

Method

According to PRISMA guidelines, we searched five electronic databases (EMBASE, Web of Science, Medline, CINAHL, and PsychINFO) for articles published between January 2011 and August 2022 on observational studies of older people with a cognitive assessment and/or cognitive impairment diagnosis and recording of falls. Their quality was reviewed according to STROBE checklist.

Result

We selected 42 of the 4934 initially retrieved publications. In 22 retrospective studies, a statistically significant association between falls and cognitive status was found in only 15 of the 37 comparisons (38%). Of the 27 cross‐sectional analyses in prospective studies, only 8 (30%) were positive and significant. We counted 4 longitudinal analyses, half of which suggested a causal relationship between falls and cognitive impairment. The investigational methods varied markedly from one study to another.

Conclusion

It is still not clear whether falls are associated with cognitive imapirment, no dementia. Data in favor of a causal relationship are scarce. Further studies are needed to clarify their relationship.
Novel Multimodal Imaging Framework for Synaptic Integrity Characterization in Alzheimer’s Disease
Authors: Kim Woo Sik , Kim Sung‐Woo , Sohn Jun Young , Lee Wha‐Jin , Seong Joon‐Kyung
Published: December 2023

Background

Dynamic loss of synapses is well understood to be a crucial endpoint in many neurodegenerative diseases especially that of Alzheimer’s Disease (AD). Hence, successful in vivo characterization of synaptic integrity (SI) provides huge potential for opportunities in therapeutics targeting synaptic damage restoration. Though recent studies using synaptic glycoprotein 2A (SV2A) PET imaging remains as the most direct measure of SI, such methods are not readily available for clinical applications. Here, we examine a new framework for in vivo characterization of SI in the AD continuum by incorporating widely available imaging parameters such as atrophy, connectivity, and neuronal metabolism.

Method

53 amyloid‐negative cognitively normal (CN‐), 92 amyloid‐positive mild cognitive impairment (MCI+), and 50 amyloid‐positive AD (AD+) subjects with T1‐weighted MRI, diffusion‐weighted MRI and 18F‐fluorodeoxyglucose (FDG) PET images were collected from ADNI. Selected imaging modalities were each theorized to portray distinct parts of SI such as pre‐synaptic disruption, synaptic connectivity, and synaptic dysfunction. Hence, using an exogenous common factor analysis model, with each modality measures as primary manifestation variables, an amalgamated regional SI score was calculated. Using regional values, factor analysis was implemented again to produce global SI scores for each subject. Regional scores were normalized and adjusted for age, sex, and education for groupwise comparison.

Result

Regional SI W‐scores showed progressive decline along the AD continuum in the entorhinal, lateral temporal, lateral parietal, and isthmus cingulate cortices, showing significant differences among most regions between CN‐ and AD+ groups. Bilateral entorhinal and isthmus cingulate cortices and left inferior temporal region showed strong significant differences between CN‐ and MCI+ groups, suggesting early synaptic loss in these areas, which agree well with previous results from SV2A PET studies. Global scores also declined significantly through disease progression and showed associations with decreased cognitive performance as measured by MMSE and CDR‐SOB.

Conclusion

Various neuroimaging biomarkers have been extensively verified to observe different traits of AD, yet successful characterization of SI without SV2A PET is first to our knowledge. Our model has shown that synaptic change can be indirectly visualized using widely available imaging modalities, providing immense opportunities for applications in both clinical and research contexts.
CAM therapy initiative for Alzheimer’s patients : Asian perspectives
Authors: Rohan S P , Patil Y , Verma N
Published: December 2023

Background

In resource‐poor‐settings, Unlike Western nations monitoring Alzheimer’s‐treatment‐Adherence is low priority due to lack of training modules/funds/expertise. drug‐toxicity, social stigma causes high‐incidence of withdrawal from therapy. Hence our we‐analyzed locally available Complementary‐Alternative Medicines [CAM] in Alzheimer’s‐cases

Facilities for diagnosis/treatment located in major‐cities &are unaffordable to >75%. ADR’s & social stigma worsened situation. CAM must be incorporated along with standard DRUG’s to reduce ADR’s & control symptoms to get better treatment‐Adherence. Provide CAM to Traditional‐faith‐hearers. To assess CAM response to pain/fatigue/Myalgia/bed‐sores/wt‐loss, feeling of hopelessness, Dementia. Hence we combined CAM with standard‐drugs.

Method

n = 72 cases aged 60‐70 years enrolled. 30% females, 70% males. self report questionnaire distributed in NGO clinic. Mud therapy 60%, Bach‐flower 40%, Accupressure/Accupuncture 80%, Hydrotherapy 10%, Hypnotherapy 70%, ayurvedic therapy 80%, 60% on Unani, 50% Homeopathic, 60% Herbal‐Oil‐TFH massage therapy, 30% Aromatherapy.

Result

patients treated in 7 CAM sessions. responses evaluated by feedback‐Performa periodically to modify treatment. Symptom relief 92%, Psycholocal mood elevation 52%, willingness to shift back to std‐drug thrapy 80%. CAM 80% cheaper compared to std drugs

Conclusion

80% patients used & preferred CAMs. CAM effectively compliments Alzheimer’s treatment‐adherence. Community NGO’s must be part of such efforts to evolve newer concepts in Adherence. Realizing divergent versions of CAM multicentre study needed.
Assessing utility of imaging based biomarker to differentiate pathologically classified frontotemporal lobar degeneration syndromes
Authors: Hwang Yun Tae , Halliday Glenda M , Piguet Olivier , Burrell James R
Published: December 2023

Background

Frontotemporal lobar degeneration (FTLD) comprises distinct neuropathological entities that present as several overlapping clinical syndromes. Two main pathological inclusions are identified in FTLD – TDP‐43, and tau itself further subdivided into 4 repeat (e.g., PSP‐tau and CBD‐tau) groups. Clinicopathological correlation is poor, at ∼60%. In vivo sensitive and specific biomarkers are needed to improve pathological diagnosis for clinical trials.

The midbrain‐pons ratio (MP) is an imaging biomarker that has been shown to differentiate PSP‐tau from Parkinson’s disease and multisystems atrophy, as well as clinically defined progressive supranulclear palsy from other FTLD syndromes.

We examined whether the MP at presentation could distinguish PSP‐tau from controls and Alzheimer’s disease (AD), as well as from other FTLD pathologies.

Method

Participants in a clinical cohort‐brain bank program based at Brain and Mind Centre, Sydney, Australia, with FTLD pathologies were included, as were matched healthy Controls and clinically diagnosed AD patients. The midbrain and pons were manually traced from the sagittal MRI slice at the midline at the initial clinical assessment of all the participants for comparison.

Result

In total, 65 participants were included in the study – 42 with FTLD (13 PSP‐tau, 6 CBD‐tau, 23 TDP‐43), 11 AD and 12 control participants; no patients with Pick’s disease were available for inclusion. Only 6/13 PSP‐tau patients, 1/6 CBD‐tau patients and 18/23 individuals with TDP‐43 were clinically diagnosed with PSP, CBS, and FTD respectively. The MP differed significantly in the PSP‐tau group compared to the control, AD, and other FTLD groups, including the CBD‐tau group. Using relevant cut off scores, positive predictive values of 90‐100% were achieved in distinguishing PSP‐tau from controls, AD, and other FTLD pathologies.

Conclusion

The MP is a useful in vivo biomarker to identify individuals with PSP‐tau. It can distinguish PSP‐tau from controls, AD, and other FTLD pathologies with high PPVs, even CBD‐tau, another important tauopathy often causing a similar clinical presentation. The PPVs achieved in using the MP were similar to those achieved using CSF and PET biomarkers of amyloid to predict AD pathology. The MP should be considered for routine use in clinical practice and selection into trials of anti‐PSP‐tau therapies.
Association of cognitive reserve indicator with cognitive decline and structural brain differences in mid‐ and late life: a large population‐based cohort study
Authors: Yang Wenzhe , Wang Jiao , Guo Jie , Dove Abigail , Qi Xiuying , Xu Weili
Published: December 2023

Background

Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to reduced dementia risk in late life. However, the association between CR and brain imaging measures, especially in mid‐life, is unclear. We aimed to explore the association of CR with cognitive decline and structural brain differences in mid‐ and late life.

Method

Within the UK Biobank, 42,301 dementia‐free participants aged 40‐70 were followed for a median of 9 (interquartile range: 8 to 10) years. Latent class analysis was used to generate an indicator of CR (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities at baseline. Cognitive tests for global and domain‐specific cognitive function were administrated at baseline and follow‐up. A subsample (n = 34,041) underwent brain magnetic resonance imaging (MRI) scans at the follow‐up examination. Volumes of total brain, white matter, grey matter, hippocampus, and white matter hyperintensities (TBV, WMV, GMV, HV, and WMHV) were assessed. Data were analyzed using mixed‐effects models and linear regression.

Result

At baseline, 16,032 (37.90%), 10,709 (25.32%), and 15,560 (36.78%) participants had low, moderate, and high levels of CR, respectively. In multi‐adjusted mixed‐effects models, compared to low CR, high CR was associated with a slower decline in global cognitive function (β [95% confidence interval, CI]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). In MRI data analysis, high CR was related to lesser TBV (‐0.03 [‐0.04, ‐0.02]), WMV (‐0.03 [‐0.04, ‐0.02], GMV (‐0.02 [‐0.04, ‐0.01]), and WMHV (‐0.03 [‐0.05, ‐0.002]), but greater HV (0.04 [0.02, 0.06]) compared to low CR. In analyses stratified by baseline age, the significant associations between high CR and global cognition and TBV were present among both mid‐life (<60 years) and late‐life (≥60 years) participants. The CR‐cognitive decline association remained significant after additional adjustment for MRI measures.

Conclusion

Higher CR is associated with slower cognitive decline, lesser TBV, greater HV, and lower microvascular burden, especially in mid‐life. The protective role of high CR on cognition is independent of structural brain differences.