bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing an occupational telerehabilitation program for caregivers of people with dementia to increase their ability to care and reduce burden
Authors: Giovanni Orientina Miriam Di , Chinaglia Cinzia Negri , Petrucci Bianca Maria , Fritzsching Daniela Matilde , Fabbo Andrea
Published: December 2023

Background

People with dementia (PwD) require high levels of care, most of which is provided by either family or informal caregivers. Psychosocial interventions have been demonstrated to reduce caregiver burden and delay nursing home admission. Telemedicine could provide caregivers access to such interventions, increasing their sense of competence and resilience.

Method

Through a co‐design process involving geriatricians, psychologists, neurologists, nurses, occupational therapists and 25 dyads, a telerehabilitation program has been developed and tested through a 12‐months Beta Test protocol. The program comprises a multidimensional clinical assessment and a telerehabilitation plan. Whilst occupational therapists act as care manager interface towards caregivers through a telemedicine platform, a multidisciplinary team including nurses, psychologists and geriatricians, regularly oversees each plan and delivers interventions whenever required.

Results

Almost all caregivers were spouses or children (22 out of 25). 79% were female and 59% lived with the care recipient in the same household. The average age of caregivers was 63,72 and Zarit index 36,88. On average PwD’s age was 83,75, Barthel Index 61,27, IADL 0,97, NPI Index 24,86 with 4,8 BPSD. The program has required on average 18,8 sessions per caregiver: which comprised of 4,5 sessions for multidimensional evaluation of both PwD and caregiver, 9,1 sessions for the execution of the telerehabilitation plan and 5,2 sessions for follow up. Sessions could range from 45 minutes (clinical scales‐based assessment) to 10 minutes (follow up). 48% of telerehabilitation sessions addressed BPSD, 17% provided emotional support, 14% supported caregivers in ADL activities, 11% addressed comorbidities and 10% addressed other issues (communication and cognition). A self‐developed caregivers' reported outcome questionnaire (24 responders out of 25) reported that 88% of caregivers improved their health literacy, 87% their sense of competence and 97% felt emotionally supported. After at least 6 months, a follow up analysis on 13 PwD and 10 family caregivers, NPI Index has improved on average by 41% while Zarit Index by 16%. Average yearly cost of the program reached 2 euro per day per dyad.

Conclusions

The beta test showed encouraging outcomes in terms of caregivers’ satisfaction that require further investigation in terms of clinical outcomes and cost‐effectiveness.
Chronic Exposure of 5‐Alpha Reductase Inhibitor in Young Male Rats Induces Not Only Metabolic Disturbance, But Also Depressive‐Like Behaviors as Similar with Obese Condition
Authors: Saengmearnuparp Thiraphat , Pintana Hiranya , Apaijai Nattayaporn , Chunchai Titikorn , Lojanapiwat Bannakij , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: December 2023

Background

Finasteride (FIN), a 5‐alpha reductase inhibitor (5‐ARIs), is one of the drugs approved for the treatment of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH). AGA has been found to be associated with obesity. Obesity and AGA themselves often co‐occurs with anxiety and depression. Nevertheless, several studies reported adverse effects of FIN on anxiety and depression, especially in young men. A previous study also reported that FIN caused anxiety and depression in male rats; however, the effects of chronic FIN exposure in young obese condition has not been investigated.

Method

Twenty male Wistar rats (8‐week‐old) were divided into two groups (N = 10/group) to feed with either normal diet (ND) or high‐fat diet (HFD) for 18 weeks. At week 13, rats in each dietary group were subdivided into two subgroups to treat with either vehicle as control or FIN (5 mg/kg/day) via oral gavage. At the end of the experimental protocol, the anxiety/depression‐like behaviors were measured using the Elevated‐Plus Maze (EPM) and the Splash Test (ST), while the Open‐Field Test (OFT) was examined for locomotor activity. In addition, blood in each rat was collected for determining the metabolic profiles.

Result

HFD‐fed rats developed obesity and hypercholesterolemia, with an increase in systemic oxidative stress (Figure 1A‐C). Anxiety and depressive‐like behaviors were observed in vehicle‐treated HFD‐fed rats, as indicated by decreasing % preference index in the open arm of EPM and grooming time in ST (Figure 1D‐E). FIN treated ND‐fed rats also showed depression‐like behaviors, similar to those in vehicle‐treated HFD‐fed rats (Figure 1E). Although FIN increased plasma cholesterol levels in HFD‐fed rats, it did not aggravate anxiety and depression‐like behaviors in HFD‐fed rats. Regarding the locomotor activity, no significant difference was found among all groups. (Figure 1F).

Conclusion

All of these findings suggest that FIN exposure induced metabolic disturbance, and depression‐like behaviors as similar to obesity without the aggravating effects of FIN and obesity on depressive‐like behaviors.
Macular vessel density in the superficial plexus is not associated to cerebrovascular damage in non‐demented individuals: data from the NORFACE cohort
Authors: Marquié Marta , García‐Sánchez Ainhoa , Sotolongo‐Grau Oscar , Tartari Juan Pablo , Sanabria Angela , Esteban‐De Antonio Ester , Pérez Alba , Castilla‐Martí Miguel , Castilla‐Martí Luis , Martínez Joan , Alarcón‐Martín Emilio , Alegret Montserrat , Aguilera Núria , Vivas Assumpta , M Gómez‐Chiari , Escudero José Miguel , Tejero Miguel Angel , Tárraga Lluís , Ruiz Agustin , Boada Mercè
Published: December 2023

Background

Optical Coherence Tomography angiography (OCT‐A) is a novel tool that allows the detection of retinal vascular changes. The comparison of OCT‐A measures with brain vascular burden is essential to validate the former as a surrogate of cerebrovascular damage and biomarker of cognitive decline. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus assessed by OCT‐A with measures of cerebrovascular pathology quantified by brain magnetic resonance imaging (MRI) in a cohort of non‐demented individuals.

Method

Clinical, demographical, APOE ε4 status, amyloid status, OCT‐A and brain MRI data from non‐demented participants of the FACEHBI and BIOFACE studies were included. We analyzed the association of macular VD in four quadrants (superior, nasal, inferior and temporal) with brain vascular burden using the Fazekas scale scores (dichotomized in two categories, 0‐1 vs 2‐3), assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) quantified by Freesurfer assessed in a multiple regression analysis. We additionally explored the associations of macular VD with hippocampal volume, ventricles volume and Alzheimer Disease cortical signature (ADCS) thickness assessed in a multiple regression analysis. All analyses were adjusted for age and dyslipidemia.

Result

The study cohort comprised 188 participants: 89 with subjective cognitive decline (SCD) and 99 with mild cognitive impairment (MCI). Logistic regression analysis showed no significant differences of regional macular VD between the two Fazekas groups (all, p>0.05). Multiple regression analysis showed no significant association of regional macular VD with the volume of WMH (all, p>0.05). Macular VD in the nasal and inferior quadrants were positively associated with hippocampal volume (p = 0.009 and p = 0.021, respectively), but no association was detected with ventricles volume or ADCS thickness (both p>0.05).

Conclusion

Our study showed that retinal vascular measures (regional macular VD in the superficial vascular plexus) assessed by OCT‐A were not associated with brain vascular damage quantified by the Fazekas scale and the WMH burden n in a cohort of non‐demented research participants with SCD and MCI.
Longitudinal factors associated with living well in people with mild‐to‐moderate dementia: initial findings from the IDEAL and IDEAL‐2 cohorts over 6 years
Authors: Matthews Fiona E , Gamble Laura D , Clare Linda
Published: December 2023

Background

Understanding the factors associated with quality of life can help us become more effective in optimizing the potential for people with mild‐to‐moderate dementia to ‘live well’ with the condition. Identifying individuals at risk of declining could help to target support more appropriately.

Methods

We used longitudinal data from 1749 individuals with mild‐to‐moderate dementia participating in the IDEAL and IDEAL‐2 studies. Assessments took place on entry and followed up at 12, 24, 48, 72 and 96 months. Using mixed effects modelling we examined change in quality of life since time of diagnosis, and looked at time‐invariant and time‐varying measures and their association with decline in quality of life.

Results

There was no change in mean quality of life in the years following diagnosis. However, we were able to identify some individuals whose quality of life declined by varying amounts and found that a larger decline was associated with being male and older, and that those with a decline in quality of life had worsening cognitive function and increasing depression in the years following diagnosis.

Conclusions

Quality of life does not decline for the majority of people following a diagnosis of dementia. However, for those that did decline we were able to identify some factors associated with this decline. This model allows us to investigate further factors that may influence living well in people with dementia, helping to identify potential factors for intervention.
Dementia subtypes and quality of life in people with mild‐to‐moderate dementia: longitudinal findings from the IDEAL and IDEAL‐2 cohorts over 6 years
Authors: Clare Linda , Gamble Laura D , Martyr Anthony , Matthews Fiona E
Published: December 2023

Background

The heterogeneity of symptoms across dementia subtypes may influence the capability of people with dementia to ‘live well’. We investigated how quality of life varies across dementia subtypes and over time.

Method

We assessed 1749 individuals with mild‐to‐moderate dementia on entry to the IDEAL or IDEAL‐2 studies and followed them up at 12, 24, 48, 72 and 96 months. We used mixed effects models to examine whether quality of life varied by dementia subtype at the time of diagnosis and how quality of life trajectories changed over time.

Result

52.4% of participants had a diagnosis of Alzheimer’s disease, 10.2% vascular dementia, and 19.8% mixed Alzheimer’s and vascular dementia. Of the rarer subtypes, 5.7% had frontotemporal dementia, 4.2% had Parkinson’s disease dementia and 5.3% had dementia with Lewy bodies, with 2.4% having other/mixed dementias. The strongest associations between dementia subtype and quality of life were seen at the time of diagnosis. Compared to individuals with Alzheimer’s disease, people with Parkinson’s disease dementia (‐4.89, 95% CI ‐6.60 ‐ ‐3.17) and dementia with Lewy bodies (‐4.90, 95% CI ‐6.38 ‐ ‐3.42) had relatively poor quality of life. People with vascular dementia (‐2.45, 95% CI ‐3.55 ‐ ‐1.35) and mixed Alzheimer’s and vascular dementia (‐1.70, 95% CI ‐2.47 ‐ ‐0.92) had somewhat poorer quality of life, but the difference was less marked. There was no difference between people with Alzheimer’s disease and people with frontotemporal dementia (‐0.39, 95% CI ‐1.73 – 0.95). There was little change in quality of life over time and we found no differences in quality of life trajectories according to dementia subtype.

Conclusion

At the time of diagnosis, quality of life already differs according to dementia subtype, and this pattern is maintained over time. People with Parkinsonian dementias in particular may need extra support with the challenges they face.
Masupirdine (SUVN‐502) for the Potential Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type: Preliminary Efficacy and Phase‐3 Study Design
Authors: Nirogi Ramakrishna , Abraham Renny , Ravula Jyothsna , Jetta Satish , Benade Vijay , Shinde Anil K , Rasheed Mohammed Abdul , Badange Rajesh Kumar , Goyal Vinod Kumar , Palacharla Veera Raghava Chowdary , Subramanian Ramkumar , Jayarajan Pradeep
Published: December 2023

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with manifestations in cognitive, functional and neuropsychiatric symptoms (NPS). Agitation is one of the most prevalent and challenging NPS to manage. Antipsychotics are widely used for the pharmacological management of agitation. However, they offer modest efficacy, and the side effects are substantial.

Serotonin‐6 receptor (5‐HT6) blockade may have therapeutic utility in the management of disorders associated with mood and behavior. Masupirdine is a potent and selective 5‐HT6 receptor antagonist.

Method

Masupirdine has been evaluated in a phase‐2, 26‐week proof‐of‐concept clinical study (NCT02580305). Subgroup analyses of study results based on the neuropsychiatric inventory scale was carried out. Masupirdine was also evaluated in animal models to assess its effect on behavior and brain neurotransmitters modulations.

A double‐blind, randomized, placebo‐controlled, parallel group, adequately powered global phase‐3 study is in progress to evaluate the efficacy, safety, tolerability, and pharmacokinetics of masupirdine for the treatment of agitation in participants with dementia of the Alzheimer’s type (NCT05397639). A total of 375 patients are planned to be enrolled in the study who will be randomly assigned to receive either 50 mg masupirdine or 100 mg masupirdine or placebo. Patients will be treated for 12 weeks. The primary efficacy endpoint of this study is the Cohen‐Mansfield Agitation Inventory items score aligning to the international psychogeriatric association agitation criteria domains (physical aggression, excessive motor activity, and verbal aggression) and the key secondary endpoint is improvement in modified Alzheimer’s Disease Cooperative Study‐Clinical Global Impression of Change score as related to agitation.

Result

The observations from the post hoc analysis of phase‐2 clinical study in AD patients and animal models support the potential beneficial effects of masupirdine on agitation.

The phase‐3 study has been initiated in USA and Europe, and the subject enrolment is expected to be completed by Q3 2024.

Conclusion

The need for new treatments for the management of agitation is significant and unmet. The Phase‐3 study results will inform the utility of masupirdine for the potential treatment of agitation in patients with dementia of Alzheimer’s type. Phase‐3 study data readout is anticipated in Q1/Q2 2025.
Longitudinal patterns of behavioral and psychological symptoms of dementia in community‐dwelling older people
Authors: Arai Asuna , Katsumata Yuriko
Published: December 2023

Background

Behavioral and psychological symptoms of dementia (BPSD) exhibit fluctuate by symptoms. This can cause difficulty for caregivers in addressing symptoms and a greater care burden. Few studies have analyzed the longitudinal course of multiple BPSD together. We aimed to identify the trajectory groups of 12 BPSD symptoms and assess the predictors of trajectory group membership.

Method

Data were drawn from the National Alzheimer’s Coordinating Center Uniform Data Set comprising participants who were followed up approximately annually in the United States. We examined home‐dwelling participants who were followed‐up for at least 1 year from 2015 to 2020. Individuals with cognitive decline (Clinical Dementia Rating of more than 0.5 and diagnosis of mild cognitive impairment or dementia) were included (n = 1,585). Twelve symptoms of BPSD were measured using the Neuropsychiatric Inventory. We used group‐based multi‐trajectory models to identify latent trajectory groups. Multinomial logistic regression analysis was conducted to assess participants’ characteristics at baseline associated with trajectory groups.

Result

Among participants, mean age was 75.7 years, median annual number of visits was 3 (interquartile range: 2‐5 visits), 44% were female, 74% lived with their spouse/partner, and 38% were able to live independently. Four trajectory groups were identified. One group showed relatively higher levels of all symptoms across years. In two groups, moderate levels of agitation, irritability, and depression, and moderate levels of apathy, appetite disturbances, and hallucinations were observed. The fourth group exhibited lower levels of all symptoms. Multinomial logistic regression models revealed that, compared with the lower‐level group, older age was associated with lower odds of other group membership. The level of dependence and cognitive decline were associated with higher odds of other group membership, although their interaction indicated lower odds. Male was a predictor of higher‐level group. Living with someone was a predictor for a group with moderate levels of apathy, appetite disturbances, and hallucinations.

Conclusion

We identified at least four trajectories in 12 BPSD symptoms over 5 years, and their common and specific predictors among community‐dwelling people with dementia. Inferring individual group membership using these predictors may be helpful for determining appropriate measures for addressing expected BPSD.
Digital Endpoints for Assessing Instrumental Activities of Daily Living in Mild Cognitive Impairment: A Systematic Review
Authors: Lawson Lauren , Ardle Ríona Mc , Wilson Sarah , Beswick Emily , Karimi Radin , Slight Sarah
Published: December 2023

Background

Impairments in instrumental activities of daily living (IADLs) can be subtle indicators of cognitive decline. By measuring declining IADLs in individuals with Mild Cognitive Impairment (MCI), we may be able to identify those who are at risk of progression to dementia and aid early intervention strategies. Digital technologies (e.g., wearables/ambient sensors) can continuously and objectively assess IADL‐related behaviours. However, it is unclear in the literature what digital methods and metrics have been used to assess IADL‐related behaviours in MCI, and what differences have been observed between MCI and normal ageing. We conducted a systematic review to address this knowledge gap.

Method

Eight databases (CINAHL/Embase/Medline/ProQuest/PsycInfo/PubMed/Web of Science/Scopus) were searched using key terms. Studies published between 2004‐2022 that used continuous, remote, digital technology to assess IADL‐related behaviours in people with MCI were included. Exclusion criteria included populations with diagnoses of other conditions that may have impacted cognition or function, research conducted in aged‐care facilities, or that had used scripted tasks. IADL‐related behaviours were taken from existing assessments and sorted into relevant domains (e.g., Activities Outside of the Home; Everyday Technology Use). This review was registered with PROSPERO (CRD42022326861) and followed the PRISMA guidelines.

Result

Fifteen articles were included from 16,099 identified titles. Eleven different technologies were used to assess IADL‐related behaviours, with motion sensors the most common. Ambient technology was used by 93% (n = 14) of studies. Only two studies measured user acceptability of technologies, with >80% of participants providing positive feedback. Seventy‐nine digital metrics were reported; computer use time and time out‐of‐home were the most commonly used. Two studies reported significant decreases in IADLs in the Activities Outside of Home domain for people with MCI compared to normal ageing. Two studies reported significant decreases in Everyday Technology Use, and one study reported a significant decrease in IADLs related to Orientation for people with MCI compared to normal ageing.

Conclusion

Findings from this review will inform the selection of tools to digitally assess IADL‐related behaviours in populations with MCI. We recommend standardisation and increased validation of digital methods and metrics used to continuously and remotely assess IADLs.
UK Biobank imaging in a memory clinic population: associations between imaging‐derived phenotypes and cognition in the Oxford Brain Health Clinic
Authors: Gillis Grace , Bhalerao Gaurav V , O'Donoghue M Clare , Blane Jasmine , Mitchell Robert , Martos Lola , Raymont Vanessa , Mackay Clare , Griffanti Ludovica
Published: December 2023

Background

Since August 2020, the Oxford Brain Health Clinic (BHC) has seen over 200 NHS memory clinic patients (O’Donoghue et al., 2022). In addition to high‐quality cognitive and lifestyle assessments and opportunities for research participation, patients receive a clinical MRI scan (T1‐weighted, T2‐FLAIR, and SWI) and can consent to additional research scans (diffusion MRI – dMRI, resting‐state functional MRI – rfMRI, and arterial spin labelling ‐ ASL) aligned to the UK Biobank (Griffanti et al., 2022). In this project, we aimed to automatically extract imaging‐derived phenotypes (IDPs) from the different imaging modalities acquired at the BHC and perform unimodal group‐level analyses to explore associations with cognition and diagnoses in this real‐world memory clinic population.

Method

As of January 2023, scans were analysed from 176 BHC patients, 101 of whom completed the additional research MRI scans. Cognitive scores (ACE‐III total score, N = 166) were available from the BHC appointment, and subsequent diagnoses (N = 118) were extracted from electronic healthcare records. Scans were processed using the UK Biobank pipeline (Alfaro‐Almagro et al., 2018), adapted to include previously described modifications (Griffanti et al., 2022). All IDPs were deconfounded for age, sex, and head size. We calculated Spearman correlations with ACE‐III cognitive scores and group comparisons (Kruskal‐Wallis tests) between 3 diagnostic groups: dementia, MCI, and no dementia‐related diagnosis. Results were corrected for multiple comparisons (false discovery rate with Benjamini‐Hochberg procedure; FDR‐adjusted p = 0.000016).

Result

11 IDPs significantly correlated with ACE‐III (Figure 1). Four voxel‐based morphometry temporal lobe measures, 3 FreeSurfer temporal lobe measures, FIRST left hippocampal volume, and SIENAX peripheral grey matter volume positively correlated with ACE‐III, in line with known dementia‐related atrophy patterns (Figure 2). dMRI mean diffusivity in the bilateral parahippocampal part of the cingulum negatively correlated with ACE‐III, highlighting white matter disruption (Figure 3). No FDR‐corrected differences were found between diagnostic groups.

Conclusion

Using an unselected patient population, all of whom have a degree of memory problems, this work provides real‐world validation of associations that are well‐established in the research context. This represents a key step towards integrating research‐quality imaging in the memory clinic. Imaging and clinical variables are planned to be available through DPUK.
SUVN‐I6107: A True Positive Allosteric Modulator (PAM) at Muscarinic M1 Receptors for the Treatment of Cognitive Disorders
Authors: Palacharla Veera Raghava Chowdary , Guduru Naga Sai Soma Chandra Sekhar , Medapati Rajesh Babu , Srirangavaram Maheshwari , Grandhi Venkata Ramalingayya , Ganuga Narender , Badange Rajesh Kumar , Nakka Harish , Subramanian Ramkumar , Nirogi Ramakrishna
Published: December 2023

Background

Muscarinic acetylcholine receptors belong to the family of G‐protein coupled receptors and are expressed widely throughout the body. Muscarinic receptors have been implicated in the pathophysiology of various central nervous system disorders. M1 subtype of muscarinic receptors play a crucial role in cognition, attention, and sensory processing. The discovery and development of selective ligands targeting M1 subtype have been unsuccessful largely due to the highly conservative orthosteric binding site. Thus, ligands that selectively bind to a less conserved allosteric site of M1 receptors and positively modulate the orthosteric site may circumvent the selectivity issues as posed by orthosteric ligands.

Method

SUVN‐I6107 is a clinical candidate identified from the M1 positive allosteric modulator (M1‐PAM) program. The effects of SUVN‐I6107 on the allosteric site of the M1 receptor were evaluated using the reporter gene assay. Binding liability towards orthosteric sites across all the muscarinic receptor subtypes was also evaluated. The pharmacokinetic properties of SUVN‐I6107 were studied both in rodent and non‐rodent species. The pro‐cognitive potential of SUVN‐I6107 was evaluated in diverse animal models of learning and memory. The safety of SUVN‐I6107 was assessed using various in vitro and in vivo systems.

Result

SUVN‐I6107 was found to be a selective M1‐PAM with no agonistic activity at Muscarinic M1 and selective across other muscarinic receptor subtypes. SUVN‐I6107 showed good oral bioavailability in rat, dog and monkey. It also has excellent brain penetration with adequate protein free fraction. SUVN‐I6107 reversed the delay‐induced memory deficit in object recognition task. It also attenuated scopolamine‐induced memory deficit in the object recognition as well as contextual fear conditioning task. SUVN‐I6107 enhanced cerebral blood flow, potentiated the effects of donepezil and promoted non‐amyloidogenic amyloid precursor protein processing in rats. SUVN‐I6107 is devoid of side effects associated with the stimulation of the cholinergic system. SUVN‐I6107 was found to be safe in the safety pharmacology and phase‐1 enabling animal toxicity studies.

Conclusion

SUVN‐I6107, a novel, potent and selective M1‐PAM demonstrated efficacy in animal models and devoid of cholinergic side effects
Hospital‐to‐home care transition for dementia patients and family care partners: communication, decision‐making, and support experience of a culturally diverse sample
Authors: Kwak Jung , Kvale Elizabeth A , Mills Sarah , Patel Snehal , Mancuso Claire E , Oppong Kwaku Duah
Published: December 2023

Background

Persons living with dementia (PLWD) are twice as likely to be hospitalized than non‐dementia peers, and while hospitalized, more likely to suffer from delirium, falls, procedure‐related complications, and death. PLWDs and their care partners (CPs) need support and preparation for hospital‐to‐home transition to avoid unnecessary readmission to hospitals. The current study aims to identify and examine communication, decision‐making, and caregiver support experience of racially and financially diverse PLWDs/CP dyads during hospital‐to‐home care transition in the U.S.

Method

We analyzed preliminary data from an ongoing mixed methods study of care transition experience of hospitalized PLWD/CP dyads. We used survey and hospital case notes data from 22 dyads and in‐depth interviews with 12 CPs recruited from two urban hospitals. We conducted descriptive and content analysis with quantitative and qualitative data.

Result

Half of PLWDs were non‐white (50%), frail with recent history of fall (68%) or hospitalization (50%) in the last three months, lacked advance directives (46%), and received palliative care consult while hospitalized (77%). Majority of CPs were non‐White (68%), PLWD’s adult child/grandchild (64%), and reported knowing a little or not much at all about dementia (82%). Themes on CP communication, decision‐making and caregiving support emerged: CPs find surrogate decision‐making difficult; proactive palliative care prepares CPs for terminal trajectory of dementia; CPs need education and training on hands‐on caregiving tasks to keep PLWDs safe and comfortable at home; and CPs’ social needs need to be addressed to achieve goals of care for PLWDs.

Conclusion

PLWDs and CPs need education, training, coaching, and individualized support during care transitions in order to develop self‐efficacy and maintain resilience. Palliative care, currently offered in over 80% of U.S. hospitals, provides important education and support for PLWDs and CPs. However, palliative care support ends after discharge for most families. Findings from our study suggest that continuing comprehensive palliative care support after discharge may be needed, when PLWD and CPs may need support the most. Future studies should examine needs of PLWDs and CPs living in communities and the role of palliative care to address informational and support needs.
Omics‐Imaging Data Integration via Mediation Analysis with High‐Dimensional Exposures and Mediators
Authors: Zhao Yi , Li Lexin
Published: December 2023

Background

Multimodal technologies have transformed AD research in recent years, by collecting different types of data from the same group of subjects and enabling the investigation of complex interrelated mechanisms underlying AD development.

Method

In this article, a mediation analysis approach with high‐dimensional exposures and high‐dimensional mediators is proposed to integrate data collected from multiple platforms. The proposed method combines principal component analysis with penalized least squares estimation for a set of linear structural equation models. The former reduces the dimensionality and produces uncorrelated linear combinations of the exposure variables, whereas the latter achieves simultaneous path selection and effect estimation while allowing the mediators to be correlated.

Result

Applying the method to the AD data, it identifies numerous interesting protein peptides, brain regions, and protein‐structure‐memory paths, which are in accordance with and also supplement existing findings of AD research.

Conclusion

The proposed approach is designed to integrate multiview data via a mediation framework. Under biological mechanistic assumptions, it articulates the underlying mechanisms and interrelations between data modalities and further infers disease pathology.
Altered BOLD Signal Fluctuations in precuneus relate to inflammatory markers and vascular risk in the AD spectrum
Authors: Maass Anne , Behrenbruch Niklas , Incesoy Enise I , Brosseron Frederic , Menze Inga , Bernal Jose , Hayek Dayana , Kleineidam Luca , Bürger Katharina , Fliessbach Klaus , Laske Christoph , Perneczky Robert , Peters Oliver , Priller Josef , Schneider Anja , Spottke Annika , Teipel Stefan , Wiltfang Jens , Wolfsgruber Steffen , Yakupov Renat , Wagner Michael , Jessen Frank , Duzel Emrah , Schreiber Stefanie , Heneka Michael T. , Ziegler Gabriel
Published: December 2023

Background

Inflammation, vascular disease and Alzheimer’s Disease (AD) appear to be closely linked. We recently showed that increased vascular risk relates to certain inflammatory profiles in CSF in the DELCODE cohort (Hayek et al, AAIC 2022). Moreover, we found cerebrovascular alterations in posterior‐midline regions including precuneus in subjects at risk for AD and with cognitive impairment relative to controls (Behrenbruch et al). Here, we examined the contributions of vascular risk and related inflammatory markers to alterations in resting‐state fMRI BOLD fluctuations that are sensitive to cerebrovascular reactivity (CVR)—a proposed marker of cerebrovascular dysfunction.

Method

Leveraging resting‐state fMRI BOLD signal, we mapped voxel‐wise relative CVR (rCVR), using mean global signal as regressor, and the relative coefficient of variation (rCV). See Figure 1 for methodological details. We derived average rCV/rCVR from the precuneus as region of interest. Inflammation‐related CSF markers and AD markers (ptau181 and Aβ42/40) from CSF were available in 205 subjects with rCVR/rCV maps. A Principal component (PC) analysis on 16 inflammation‐related CSF markers previously revealed 4 PCs. PC2 and PC3 were related to higher vascular risk scores (covering hypertension, diabetes and abnormal fat metabolism based on medical reports). We used linear regression models to assess how inflammation PC scores and AD biomarkers related to precuneus rCVR or rCV (controlling for age, sex, site, education and mean framewise displacement). We also tested if rCVR/rCV was related to vascular risk or memory.

Result

Lower precuneus rCVR was predicted by higher values of the inflammatory component PC2 (mainly driven by markers CRP, C1q and FactorB), with no additional effect of other PCs or AD markers. Lower precuneus rCV was predicted by higher values of the inflammatory component PC3 (mainly driven by IP10, MCP1, MIF, CRP, C4) and by higher ptau. Lower precuneus rCVR was also related to higher vascular risk. Lower rCVR and rCV related to worse memory. Figure 2 shows supplementary correlations of individual inflammation markers.

Conclusion

Lower rCVR and rCV in the precuneus that are thought to reflect vascular dysfunction, relate to higher vascular‐risk related inflammatory markers beyond AD pathology. Their concurrent dynamics requires further investigation to understand their unique contributions to microvascular pathology.
Diagnostic accuracy of a new case‐finding tool for dementia in primary care: The Brief Assessment of Impaired Cognition Questionnaire (BASIC‐Q)
Authors: Oxbøll Anne‐Britt
Published: December 2023

Background

The aim of the project was to examine the diagnostic accuracy of BASIC‐Q (Brief Assessment of Impaired Cognition Questionnaire), a questionnaire‐based tool for detection of dementia in a community setting. Community health care professionals often see citizens who are older and therefore in risk of developing dementia or having undetected dementia. BASIC‐Q is an easy and quick (≤5 min) conversation‐based tool to be used to support community health care professionals when observing signs of dementia.

Method

The project has been carried out in collaboration with 14 general practices in Denmark in the period October 2021‐October 2022. Patients ≥ 70 years with appointment in the clinic for any given reason, were invited to participate in the study. The general practitioner or the nurse at the clinic administered BASIC‐Q ‐ consisting of four questions about orientation and three questions regarding the participants memory for both the participant and a close relative. Subsequently the participant participated in a structured telephone interview and an extended cognitive testing. Among other, the extended testing consisted of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) that together with an IADL‐evaluation (instrumental activities of daily living) and GDS‐15 (15‐item geriatric depression scale) was used as gold standard for classification of cognitive status when analyzing the sensitivity, specificity, and diagnostic accuracy of BASIC‐Q.

Result

The mean age of the total of 275 participants was 77.7 years, of which 148 were women (52.9%) and 127 were men (46.1%). Of the participants 142 (51.6%) showed no evidence of cognitive impairment, 33 (12%) showed evidence of affective disorder, and 82 (29.8%) showed indications of cognitive impairment. 18 participants (6.5%) could not be classified and were not included in the analyses.

Conclusion

BASIC‐Q is a quantifiable indicator of cognitive function. BASIC‐Q can be used as an assistive tool when health care professionals observe signs of dementia and need to decide whether to intervene.

Preliminary analyses indicate that BASIC‐Q is a reliable tool for the detection of possible dementia in primary health care. The analyses of results are still ongoing and more results regarding the BASIC‐Q’s diagnostic accuracy will follow.
Promises and Challenges of Blood Based Biomarkers of Alzheimer’s Disease and Neurodegeneration in Mild Cognitive Impairment: Importance of Non‐Alzheimer’s Aetiologies
Authors: Hamilton Calum Alexander , O'Brien John T , Heslegrave Amanda , Laban Rhiannon , Donaghy Paul C , Durcan Rory , Lawley Sarah , Barnett Nicola , Roberts Gemma , Firbank Michael J , Taylor John‐Paul , Zetterberg Henrik , Thomas Alan J
Published: December 2023

Background

Blood‐based biomarkers of Alzheimer’s disease (AD) may help to rule AD in, with particular promise at the mild cognitive impairment (MCI) stage when potential disease‐modifying treatments may be most effective. However, AD is not the only common cause of cognitive impairment: Lewy body disease and other non‐AD pathologies are common and under‐recognised. Reliance on AD‐specific biomarkers alone may therefore contribute to missed diagnosis of non‐AD aetiologies. We aimed to examine the utility of emerging AD plasma biomarkers in identifying disease‐specific MCI due to AD (MCI‐AD), MCI with Lewy bodies (MCI‐LB) and in disease‐general MCI. We also aimed to compare these with alternative disease‐general biomarkers of neurodegeneration, and examined any change over time.

Method

In a longitudinal study, plasma samples were collected for 172 participants (31 healthy controls, 48 MCI‐AD, 28 possible MCI‐LB and 65 probable MCI‐LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with Simoa assays for Alzheimer’s disease (Aβ42, Aβ40, ptau‐181) and neurodegeneration (GFAP and NfL) biomarkers.

MCI cases were differentially classified as MCI‐AD or MCI‐LB by an expert panel of old age psychiatrists, based on current consensus diagnostic criteria, and including Lewy body disease‐specific imaging biomarkers.

Age‐adjusted mixed effects models assessed any longitudinal changes over time in each biomarker, and associations with severity of cognitive impairment as assessed by the Addenbrooke’s Cognitive Examination – Revised.

Result

GFAP performed comparably to AD‐specific biomarkers in identifying any‐cause MCI (GFAP AUC = 0.75; ptau‐181 = 0.73), while maintaining good accuracy in identifying MCI‐AD specifically. AD biomarkers did not reliably distinguish MCI‐AD from MCI‐LB. Severity of cognitive impairment in any‐cause MCI and MCI‐AD was most strongly correlated with the disease‐nonspecific neurodegenerative biomarker NfL (r = 0.48, p = 0.005; cf. GFAP r = 0.23, p = 0.121), which progressively increased over time.

Conclusion

Given the high prevalence of unrecognised non‐AD pathologies at autopsy (>1/3 cases in UK brain banks), blood biomarkers of neurodegeneration may be a useful alternative to AD‐specific biomarkers in screening for neurodegenerative disease in MCI. As AD biomarkers do not reliably differentiate MCI‐AD from MCI‐LB, there is a need for disease‐specific biomarkers of synucleinopathies.
Taking care of family dementia caregivers: A qualitative examination of patient perspectives and perceived health outcomes after receiving usual care and after a digitally supported care management programme
Authors: Klein Olga A. , Karras Antonia , Hoffmann Wolfgang , Teipel Stefan , Kilimann Ingo
Published: December 2023

Background

Almost two‐thirds of people with dementia (PwD) living at home receive care from a family or other informal caregiver. Evidence shows that family caregivers experience increased physical, psychological, emotional, and social stress which, in the long term, results in adverse health outcomes. The development of effective healthcare and support management for family caregivers is vital. Therefore, our aim was to examine and compare the perceptions of participants who received a digitally supported care management programme with those who received usual care.

Method

This study was embedded within a multi‐centre, cluster randomized controlled trial (GAIN study) examining the effectiveness of a care management programme for family caregivers of people with dementia. The trial is registered at ClinicalTrials.gov (NCT04037501). Data collected through semi‐structured interviews with participants of the GAIN trial were audio recorded, transcribed and analysed using framework analysis. We developed two semi‐structured interview schedules, each tailored to the content of the group (control or intervention).

Result

We interviewed 36 dementia caregivers (30 women, six men) of whom 20 were in the intervention and 16 in the control group. The mean age was 68 years (SD 11,28, range 50‐82). The majority was the caregiver for their spouse, six were the caregiver for their parent and one was the caregiver for their aunt. The lengths of interviews varied between 15‐82 minutes with most interviews being 35 minutes long. Six themes were identified: (1) Health and well‐being before participating in GAIN (2) Use of services and support (3) Perceived health changes (4) Additional services discussed & received in the intervention group (5) Impact of study nurse support and (6) Possible improvements. Each theme had further sub‐themes and categories, which will be presented.

Conclusion

Overall, participants in the care management programme reported benefits and additional services they used as a result of being in the intervention group (e.g., rehabilitation, home adaptations, care services) compared to the control group. Having someone professional by their side was reported to be helpful and motivating. Participants of both groups also reported that they preferred house visits rather than telephone contacts. The results can be used to further improve the care management programme.
A3 receptor as a target for the treatment of Alzheimer’s disease
Authors: Farr Susan A. , Doyle Timothy M , Jacobson Kennth A. , Salvemini Daniela
Published: December 2023

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with clinical features including memory loss, cognitive impairment and dementia that affects over six million Americans. Current treatments for AD have limited efficacy due, in part, to the poorly understood multifactorial nature of the mechanisms driving AD. Our data suggests that alteration of adenosine kinase‐dependent adenosine metabolism and inadequate A3 adenosine receptor (A3AR) signaling in the central nervous system (CNS) are key to these processes. The SAMP8 mouse are a mouse model of sporadic AD exhibiting many key characteristics of AD including age‐associated impairment in learning and memory, which corresponds to age‐related increase in beta amyloid, phosphorylated tau, oxidative stress, neuroinflammation, impaired efflux across the blood‐brain barrier and increased regulatory T‐cells in the brain.

Method

We first measured expressions of ADK and A3AR in the hippocampus of 12 month old. SAMP8 mice. We then treated 11 month old SAMP8 mice with MRS5980 an A3AR receptor agonist MLN5980 every other day for 6 weeks. At the end of the 4th week of treatment, behavior tests were conducted for two weeks. Mice were tested in T‐maze, Novel Object Recognition (NORPT), elevated plus maze and open field.

Result

12 month old SAMP8 mice treated with the A3AR agonist MRS5980 had improved learning and memory in the T‐maze and NORPT compared to the vehicle treated control mice. There was no difference between the young vehicle treated SAMP8 mice and the MRS5980 treated mice. MRS5980 did not affect activity or anxiety in the open field or elevated plus mazes indicating these factors did nor contribute to improvement in learning and memory.

Conclusion

Here we identify A3AR in key cognitive centers of the brain and its expression increases with cognitive impairment in the SAMP8 AD mouse model. Moreover, adenosine kinase, an enzyme that reduces extracellular adenosine, also increased. We discovered that supplemental A3AR signaling with highly selective, orally bioavailable, CNS‐penetrant A3AR agonists reversed cognitive impairment without any confounding influence on locomotor activity or anxiety. Our results indicate that A3AR is a useful pathway to give additional insight into changes in the brain with AD potential novel therapies.
Social health and subsequent cognitive capability: examining the potential mediating roles of depression symptoms and inflammatory biomarkers
Authors: Stafford Jean , Dekhtyar Serhiy , Ning Ke , Welmer Anna‐Karin , Vetrano Davide Liborio , Grande Giulia , Marseglia Anna , Moulton Vanessa G , Mansfield Rosie , Liu Yiwen , Ploubidis George B , Gessa Giorgio Di , Richards Marcus , Davis Daniel , Patalay Praveetha , Maddock Jane
Published: December 2023

Background

Social health (SH) markers, including marital status, contact frequency, network size, and social support, have been linked with increased cognitive capability. However, the underlying mechanisms remain poorly understood. We aim to investigate whether depression symptoms and inflammatory biomarkers mediate associations between SH and cognitive outcomes.

Method

We used data from waves 1‐9 of the English Longitudinal Study of Ageing, involving 7,136 participants aged 50 or older at baseline. First, we examined associations between SH (wave 1) and depression and inflammatory biomarkers (C‐reactive protein (CRP) and fibrinogen) (wave 2) using linear regression models. Second, we tested associations between a) SH and b) depression and inflammation with subsequent standardised verbal fluency and memory in wave 3 and change between waves 3‐9, indexed using slopes derived from multilevel models. We adjusted for age, sex, socio‐economic position, cardiovascular disease, basic and instrumental activities of daily living, health behaviours, and baseline depression symptoms and cognition. We will also conduct causal mediation analysis.

Result

All SH markers, except contact frequency, were associated with lower subsequent depression, but not inflammatory biomarkers. Greater contact frequency (e.g. once‐twice a week vs 6 people vs none: β = 0.007SD/year [0.001, 0.012]), less negative (β = 0.001SD/year [0.001, 0.002]) and more positive support (β = 0.001SD/year [0.000, 0.001]) were linked with slower memory decline, and more positive support predicted slower verbal fluency decline (β = 0.001SD/year [0.000, 0.001]). Depression symptoms were associated with lower memory and verbal fluency, and faster memory decline (β = ‐0.001SD/year [‐0.001, ‐0.000]) and verbal fluency (β = ‐0.001SD/year [‐0.001, ‐0.000]). CRP was associated with lower verbal fluency (β = ‐0.02 [‐0.04, 0.00]), whereas fibrinogen was linked with faster memory decline (β = ‐0.001SD/year [‐0.003, ‐0.000]).

Conclusion

Depression symptoms and SH showed associations with subsequent cognitive capability and change. SH was linked with lower depression, but not inflammatory biomarkers. Findings highlight the potential for depression to underpin associations between SH and cognition, a pathway which we will test using causal mediation analysis. We will also examine whether findings replicate in the Swedish National Study of Aging and Care in Kungsholmen.