bluuebunny/crossref_metadata_2025 huggingface dataset:
Financial burden by chronic disease and its associated factors among aged (60+) living in India: An Evidence from 75th‐National Sample Survey (NSS)
Authors: Mishra VijayKumar
Published: June 2023

Background

Some or more chronic diseases are directly associated with standard of living, socioeconomic status, behavioural, economic support from friends/relatives and loan or monetary generated through the sales of household items/goods. However, financial stability plays an important role in handling the cost of care during hospitalization, transportation and non‐medical expenses, and to avoid further chronic conditions. These costs of care during hospitalization are key contributors among aged (60+) people living in India, especially for those who have no support from other family members or relatives. These monetary costs also vary across various social groups (castes). This study has done to understand the monetary burden due to chronic disease among aged (60+) and its associated factors in India.

Method

This study has utilized social consumption and health data from National Sample Survey, 75th round (2017‐18). The average expenditure per hospitalization case (in‐patient) due to chronic disease in aged (60+) were estimated. Generalised Linear regression modeling (GLRM) was done to understand effect of exposure variables (social group, education, household‐expenditure quintile, major source of finance, nature of treatment) on in‐patient expenses incurred on chronic disease.

Result

This study found that around 61 percent married older people were suffering from chronic morbidity in India. Around 43 percent illiterate older people suffered from any chronic diseases, which was the highest compared to highly educated elderly. The results confirm the significantly higher in‐patient expenses among the people having higher level of education [β = 1.26] compared to lower education. Also, the people belonging to Other backward caste bear significantly higher expenses compared to SC.

Conclusion

Indian aged (60+) are facing high out of pocket expenses on hospitalization due to chronic disease among. Such costs not only create financial problem but also may affect expenses on other health condition or diseases. Insurance coverage was found very weak in India, especially in rural part, and in people with low education level. Policy makers should focus on such schemes on priority basis to ensure active and health ageing in India.
Assessing awareness in severe Alzheimer’s disease
Authors: Huntley Jonathan D , Bor Daniel , Owen Adrian M , Howard Robert J
Published: June 2023

Background

There is an urgent need to understand the nature of awareness in severe AD to ensure effective person‐centred care. Transcranial Magnetic Stimulation (TMS) combined with Electroencephalography (EEG), Event Related Potentials (ERPs) and functional Magnetic Resonance Imaging (fMRI) are robust techniques for assessing awareness in clinical populations who are unable to communicate. We present novel feasibility and preliminary data on using these methods to assess capacity for consciousness and contents of awareness in severe AD.

Method

a) TMS‐EEG was performed in 6 healthy older controls and 3 people with severe AD. The perturbational complexity index (PCIST) was calculated as a measure of capacity for conscious awareness. b) ERPs were recorded during a masked visual perception paradigm and analysed for the presence of visual awareness negativity and P400 components, previously identified as associated with conscious visual perception. c) An fMRI movie‐viewing task, validated in previous studies to demonstrate activation in a fronto‐parietal network during conscious engagement with the film was also conducted.

Result

a) Participants with severe AD demonstrated a PCIST around the previously identified threshold for consciousness, suggesting reduced capacity for consciousness. b) In response to viewing faces, two patients with severe AD provisionally demonstrated similar visual awareness negativity to healthy controls. c) Healthy controls and one person with severe AD revealed spatially, but not temporally similar activation in a fronto‐parietal network, suggesting differences in conscious engagement with the movie.

Conclusion

These biomarkers provide experimental approaches to assess awareness and improve understanding and care for people with severe AD.
Venous flow disturbance links to the cognitive function in the ultrasonographical validation study
Authors: Matsuzono Kosuke , Suzuki Masayuki , Miura Kumiko , Anan Yuhei , Ozawa Tadashi , Mashiko Takafumi , Koide Reiji , Tanaka Ryota , Fujimoto Shigeru
Published: June 2023

Background

According to the dementia progression, especially in Alzheimer’s disease (AD), venous reflex disturbance may be concerned. We previously found and reported that the validation of the spontaneous echo contrast or velocities of the internal jugular vein are convenient AD diagnosis screening methods and that the venous reflux disturbance correlates with AD development (Matsuzono K et al. J Alzheimers Dis. 2021;84(2):787‐796). In order to clear the relationship between venous reflex disturbance and dementia, we performed the additional study using the transesophageal echocardiography (TEE).

Method

We performed the TEE examination and the higher brain function test to the 80 participants. According to the TEE examination, we validated 1) the spontaneous echo contrast in heart, 2) shunt including the patent foramen ovale, 3) velocities at the left atrial appendage, and 4) the plaque length at the aortic arch. According to the higher brain function, we validated the Mini‐Mental State Examination (MMSE), Hasegawa Dementia Rating Scale‐Revised (HDS‐R), and Frontal Assessment Battery (FAB).

Result

Twenty‐six (32.5%) of the 80 participants showed positive spontaneous echo contrast in the heart. All the MMSE, HDS‐R, and FAB scores of the positive group was significantly lower than that of the negative (26 vs 24, 26 vs 22.5, 14 vs 10.5, p<0.05). According to the shunt, there was no significant relationship to the cognitive function. The velocities at the left atrial appendage showed positive correlation while the plaque length at the aortic arch showed negative correlation to the cognitive function (r = 0.2).

Conclusion

In both of the internal jugular vein and of the heart, the spontaneous echo contrast significantly correlates with the cognitive impairment. Our study using the ultrasonographical examination shows the venous reflex disturbance concerns with the dementia progression.
Different levels of cognitive reserve among typical and limbic‐predominant hypometabolic subtypes of Alzheimer’s Disease
Authors: Levin Fedor , Grothe Michel J. , Dyrba Martin , Franzmeier Nicolai , Teipel Stefan
Published: June 2023

Background

Residual approaches for estimating cognitive reserve (CR) are assumed to reflect relative resilience of individuals to neuropathological change in Alzheimer’s disease (AD). In the present study, we characterized differences in CR in people expressing distinct hypometabolic subtypes of AD‐related neurodegeneration.

Method

We analyzed MRI, FDG‐PET and cognitive performance data of Aβ‐positive participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, including 58 cognitively normal (CN), 217 prodromal AD and 177 AD dementia participants. Participants’ FDG‐PET scans were classified into the two principal hypometabolic subtypes of AD – typical and limbic‐predominant – as determined previously by a data‐driven clustering analysis. W‐scores were calculated as standardized residuals from a regression model with temporoparietal gray matter (GM) volume adjusted to total intracranial volume (TIV) as the dependent variable and with memory and executive function composite scores, as well as covariates age, gender, TIV and dementia status as independent variables (Fig. 1). The scores were multiplied by “‐1” so that higher values indicated lower than expected temporoparietal GM volume at a given level of cognitive performance and therefore represented higher CR. We evaluated the effects of W‐scores on the risk of clinical progression and longitudinal cognitive decline while including temporoparietal GM as a covariate. We then compared the W‐scores between the two hypometabolic subtypes of AD.

Result

Higher W‐scores, indicating higher CR, predicted a lower risk of prodromal AD participants for the progression to AD dementia (hazards ratio = 0.32, 95%CI = [0.19;0.52]). W‐scores were also associated with a slower longitudinal cognitive decline for memory (β = 0.11,p<0.01) and language performance (β = 0.12,p = 0.017) in the subsample of CN and prodromal AD (Fig. 2). The typical hypometabolic subtype showed on average higher W‐scores than the limbic‐predominant subtype in prodromal AD and AD dementia groups.

Conclusion

Consistent with previous research, CR as assessed by W‐scores was predictive of a lower risk of clinical progression and slower longitudinal cognitive decline. The typical subtype demonstrated higher W‐scores, which suggests a stronger resilience to the impact of neuropathological change on cognition. Future analysis will investigate longitudinal changes in W‐scores and factors contributing to the observed differences, as well as potential explanations for subtype differences.
Single domain antibodies as new detectors of neurotoxic Aβ42 oligomers
Authors: Napolitano Liliana , Bigi Alessandra , Vadukul Devkee , Aprile Francesco , Chiti Fabrizio , Cecchi Cristina , Cascella Roberta
Published: June 2023

Background

The presence of extracellular amyloid β (Aβ) plaques in the brain parenchyma and intracellular neurofibrillary tangles of the hyperphosphorylated tau protein is the main hallmark of Alzheimer’s disease (AD). Aβ aggregation consists of a complex chain of nucleation events producing soluble oligomer intermediates, which are the major neurotoxic agents. The transient nature of these oligomers makes very challenge their isolation and characterization. Single domain Abs (sdAbs), composed only of a variable domain of the heavy chain with high specificity and affinity, appear as promising tools for an early accurate diagnosis and therapy for AD.

Method

An in vitro and in vivo screening of different sdAbs was performed, selecting those targeting Aβ42 oligomers with high specificity using immunoassays and the super resolution stimulated emission depletion (STED) microscopy. The ability of sdAbs to prevent Aβ42‐induced cytotoxicity in neuronal cells was investigated. Then, the sdAbs were used to detect and quantify the levels of Aβ42 assemblies in the cerebrospinal fluid (CSF) of AD patients and controls.

Result

SdAbs can detect neurotoxic Aβ assemblies and prevent the associated neuronal dysfunction in cell models. Furthermore, sdAbs significantly discriminated Aβ aggregates in the CSF.

Conclusion

All these data provide solid grounds for the understanding of the molecular basis of oligomers toxicity, thus establishing a compelling structure‐toxicity relationship. Moreover, sdAbs‐based approaches hold a great potential as they allow detection in complex mixtures such as a biological sample for an early differential diagnosis of AD, also providing therapeutic benefits.

The study was supported by Airalzh (AGYR 2020 to R.C.).
How is personalisation used in exercise for people with dementia, in what circumstances and why? A rapid realist review
Authors: Booth Vicky , Harwood Rowan H , Logan Pip A , Foster Nadine , Pugh Pearl , Graff Maud , Schneider Stefan , Wong Geoff
Published: June 2023

Background

Realist reviews are a type of systematic theory‐driven approach for making sense and evaluating the literature with the intention to identify plausible theories or models. This review will determine what literature and theoretical knowledge is available on “personalisation” in the context of exercise for people living with dementia (PwD). The aim of the review is to develop an initial programme theory that can be used to inform the development and testing of resources to support exercise interventions for PwD.

Method

Electronic databases and gg terms: personalisation, tailoring, adaptations, person‐centred, etc. Inclusion criteria were:

• PwD (any type, severity, or location)

• Exercise intervention (all forms)

• Explicit discussion of theoretical concepts or rationale to Personalisation

Articles were not excluded based on study design. A preliminary search to scope the evidence, refine search terms and criteria was undertaken before the start of this review.

Data were collected from the included articles and managed through data analysis software that accommodates both qualitative and quantitative data (Excel). The review was registered on PROSPERO and followed RAMESES guidance and publication standards.

Result

Of the 2036 articles initially found, data extraction was completed from 64, following sorting for relevance and rigour (Figure 1). An initial programme theory involving 11 context‐mechanism‐outcome configurations (CMOc) is presented (Table 1) at different socio‐ecological levels of interaction needed to underpin a personalised exercise programme for PwD.

Consideration of the individual’s identity, preference, preserved/embodied abilities, vulnerabilities, motivations (behaviour change), and their care‐giver should be acknowledged at an inter/intra‐personal level. Staff implementing the exercise programmes should have a person‐centered care approach, acknowledging concepts of personhood and using shared decision‐making. Finally, the cultural norms and expectations of the society within which the exercise programme is being conducted, and the PwD is situated within, should be considered to promote social connections rather than stigmatisation.

Conclusion

The initial programme theory explains personalisation and illustrates a novel foundation upon which to develop and refine a programme of exercise adapted specifically for PwD. Results from this review will inform data collection in the subsequent realist evaluation (e.g., interview questions).
Resting‐state dynamic functional network connectivity predicts cognition in 37,784 participants of UK Biobank
Authors: Sendi Mohammad S.E. , Zendehrouh Elaheh , Miller Robyn L , Salat David H , Calhoun Vince D
Published: June 2023

Background

Age‐related cognitive decline after 65 is a well‐known phenomenon, but little is known about how brain functional changes are related to cognitive decline. To this end, previous studies explored the link between functional network connectivity (FNC) estimated from resting‐state functional MRI (rs‐fMRI) and cognitive scores in healthy adults. FNC is often assumed to be static over time. However, this assumption runs contrary to the dynamic nature of brain FNC, and dynamic FNC (dFNC) has been recently introduced to overcome this limitation. The current study investigated the relationship between dFNC estimated from 36,263 individuals from UK Biobank and cognition.

Method

We used the resting‐state fMRI (duration: 5min) data of 37,784 (20,157 females) adults’ brains, demographic information (age:64.06± 7.51), and cognitive scores from the UK Biobank in which the cognitive scores include fluid intelligence (FI), reaction time (RT), and pairs matching (Pairs). We adapted group independent component analysis to extract 53 data‐driven components for the whole brain using a fully automated approach (Fig.1: Step1). Next, we used the sliding window and Pearson correlation to estimate the dFNC among 53 components (Fig.1: Step2). We used k‐means clustering to put dFNCs of all individuals into three separated states and calculated individual state vectors (Fig.1: Step3). Then, we estimated 32 dFNC features based on three estimated states and state vectors (Fig.1: Step4). Finally, we trained a two‐fold cross‐validation support vector regression to predict the cognitive scores (Fig.1: Step5).

Result

The estimated dFNC feature predicted FI score with high accuracy (the correlation between measure and predicted score is R = 0.043, p = 6.6e−17, Fig.2A), mean time to correctly identify match in RT task (R = 0.065, p = 1.9−34, Fig.2B), and time to complete Pairs task (R = 0.049, p = 1.3e−20, Fig.2C).

Conclusion

Here we explored the link between dFNC features and cognition in the most extensive dFNC study and found that estimated dFNC features can successfully predict cognitive scores in the UK Biobank dataset. Even though the correlation values are very low, the results are still very significant due to large N. Future study is needed to explore the difference between the subgroup with high versus low prediction accuracy.
Changes in oculo‐motor activity during a cognitive challenge can distinguish clinical stages of early Alzheimer’s disease
Authors: Sorinas Jennifer , Fernandez Gerardo , Shulz Matias , Vallejo Vanessa , Snædal Jón , Hannesdottir Kristin , Curcic Jelena
Published: June 2023

Background

The eye adapts to the demands of our behavior [1], its motor activity has proven to be a feasible method for measuring cognition in both health and disease [2]. This study assessed the sensitivity of oculo‐motor features in a benign cognitive challenge model with the purpose of identifying objective efficacy readouts for clinical drug trials in early Alzheimer’s disease (AD).

Method

Fifty participants, aged 60 to 80 years, performed a reading task in two sessions conducted the same day, morning and evening (i.e. the “cognitive challenge”), with an average inter‐session period of 9.28h, during which participants were not allowed to take naps or consume stimulating beverages. Participants were distributed across four cohorts corresponding to progressive stages of early AD [3]: 1) amyloid negative, cognitively healthy (control group), 2) amyloid positive pre‐symptomatic AD, 3) Mild Cognitive Impairment (MCI) due to AD (pre‐dementia group) and 4) mild AD (mild‐dementia group). ViewMind technology was used to track the oculo‐motor activity [4].

Result

None of the four cohorts reported increased levels of sleepiness during the challenge. However, cohorts showed significantly different oculo‐motor responses during the cognitive challenge (Table 1). The control group showed evidence of learning effects on the reading during the challenge reflected in no change in pupil size, longer saccades, less fixations and shorter gaze. Within the pre‐symptomatic group, however, a negative impact of the challenge was observed in a decrease in pupil size and increase in fixations. However, some learning effects were nevertheless seen in this cohort, in shorter gaze and longer saccades. In pre‐dementia group the learning effects were lost and participants demonstrated difficulty performing the task reflected in decreased pupil size and longer gaze. Finally, the mild‐AD participants showed an increase in fixations, longer gaze and no change in pupil size indicating a pattern of poor reading performance during the challenge.

Conclusion

Our preliminary results demonstrate that oculo‐motor activity may reflect changes in cognitive resources induced by a benign challenge in progressive clinical stages of early AD. These promising results support continued investigation into the potential of eye‐tracking during reading as a sensitive and objective measure .
Human Alzheimer’s postmortem raphe brain heterogeneity: Single cell RNAseq 10X genomics approach
Authors: Reddy Arubala P. , Peng Joyce , Mechref Yahia , Reddy Hemachandra P
Published: June 2023

Background

The complexity of subcortical brain remains unexplored due to complex neuronal structure and heterogeneity of neuronal populations in the brain. Raphe brain regulates multiple physiological events like stress, memory, feeding, sleep, movement, balance, and many others. ere we present the single cell RNAsec (scRNAseq) analysis of raphe tissue from the postmortem brains of Alzheimer’s disease Braak Stages VI and control subjects.

Method

Postmortem raphe brains acquired from NIH‐NeuroBioBank. Intact cells were collected using Cell Raft AIR System. Single cell suspension of neurons and synthesized cDNA and normalized cDNA using library preparation. The samples were processed in NextGen v3‐1 using 10X Genomics Chromium system. The library was sequenced ± 200 million PE150 reads /sample on Illumina Novaseq. The sequences were mapped against GRCh38 using Cell ranger v6.1.

Result

The data will be analyzed using 10X genomics cell ranger and Loup Browser tools. Further functional genomics tool DAVID
) v6.8 and (
IPA
) will be used to analyze heterogeneity of raphe brain and various presynaptic neuronal modulation in 1. AD and control, 2. AD and control males and 3. AD and control females. The most astringent analysis of data showed 5% mitochondrial genes, . We will also analyze the therapeutic targets and biological pathways. Heterogeneity of raphe and genes triggered in AD pathology will also be investigated.

Conclusion

The raphe connectivity to Alzheimer’s disease and other dementias was a hot‐topic in 1980s research and somehow lost interest in the last 2 decades. The concept of serotonin neuromodulation evolves in recent years due to new concept of serotonin connecting intracellular and intracellular neuromodulation, use of serotonin drug targets in behavior alterations in dementia and early depression and aggression might be a causal factor to neurodegenerative onset much before classic pathologies of the disease appear. Our study will reveal the heterogenous neuronal population in complex raphe region of the brain and how the microenvironment changes neurotransmission in the forebrain. We will present extensive analysis on neuronal population of raphe and its role in AD and healthy subjects. The results will be a AD and ADRD models to pinpoint the changes in 5HTsynthesis and neuromodulation to forebrain and cerebellum.
Evaluation of cognition with the eyelink: Saccadic eye movements in healthy subjects
Authors: Tüfekci Işıl Yağmur , Koçoğlu Koray , Boz Hatice Eraslan , Akkoyun Müge , Ekin Merve , Akdal Gülden
Published: June 2023

Background

The aim of this study is to determine the normative data of eye movements models for healthy individuals between the ages of 18‐77.

Method

76 healthy subjects were included in 3 age groups as 18‐44, 45‐59, 60+. Neuropsychological assessment with five cognitive domains, was applied. EyeLink 1000 Plus was used to record and pro‐saccade and anti‐saccade eye movement paradigms. Amplitude, latency, anticipatory saccades, express saccades, correct saccade response, corrected saccade and uncorrected saccade responses were analyzed.

Result

In antisaccade results, correct saccade response, latency, amplitude, anticipatory saccade, express saccade, corrected saccade response, uncorrected saccade were significantly different between the groups (p<0.05). Significant difference was also found in prosaccade latency (p<0.001). In the 18‐44 age group, executive functions were highly negatively correlated with antisaccade latency (r = ‐0.744, p = 0.000), and language was meanly negatively correlated with latency (r = ‐0.514, p = ‐0.010). In the 45‐59 age group, a medium level of negative correlation was observed between executive functions and latency (r = ‐0.501, p = 0.025). Language and express saccade (r = ‐0.515, p = 0.020) were meanly negatively correlated in the 45‐59 year age group. In the 60+ age group, a medium level of negative correlation was found between attention and latency (r = ‐0.414, p = 0.021). In this age group, executive functions and uncorrected saccade (r = ‐0.396, p = 0.027) were weakly negatively correlated.

Conclusion

Decline in cognitive functions that occur with aging might affect eye movements. The relationship between antisaccades and cognitive functions in our preliminary study may attract attention to antisaccades in evaluation of cognition.
Peer Mentorship with Lewy Body Disease: A protocol for co‐developing and piloting a program for post‐diagnostic support
Authors: Booi Laura , Swaffer Kate , Medsger Helen Bundy , Murphy Damian , Leroi Iracema
Published: June 2023

Background

Social isolation, loneliness and stigma are some of the most detrimental psychosocial effects of living with dementia, including Lewy Body Disease (LBD). Peer‐to‐peer support between newly diagnosed people living with LBD and more experienced people living with LBD has the potential to reap extremely positive effects for both parties, and their care partners (CP). This presentation will discuss a protocol and the developments of a project to co‐develop a peer mentorship program (PMP) with people living with LBD and their CP.

Methods

Co‐design workshops with people living with LBD and their CPs will take place to co‐develop the curriculum for the PMP. The PMP will be delivered via video conference technology. Alongside this, collaborations with volunteer, community and social enterprises will be incorporated into the project design, to maximize shared learnings from other community led peer mentorship programs. Thus far these programs include peer mentorship programs for incarcerated individuals and those living with HIV.

Results

The PMP is in the design stage and further components of this project are underway to incorporate the lived expertise of those with LBD and their CPs, as well as clinicians to the design. Recruitment of piloting participants for the PMP is expected in the second half of 2022.

Conclusion

The PMP will offer guidance for shared experiential learning so that the person living with LBD and their CP will be better educated and equipped to support themselves and each other through the care pathway. The solution offered via the PMP contributes to improving access to information in an affordable way and to becoming integrated into the post‐diagnoses care pathway as an option for social prescribing.
The relationship between inflammatory biomarker trajectory and cognitive change following elective non‐cardiac surgery in older adults
Authors: Scott David A , Silbert Brendan S , Evered Lisbeth A , O'Bryant Sid E. , Hall James
Published: June 2023

Background

Surgery in the older patient is associated with short‐ and long‐term cognitive changes, including delirium, post‐operative cognitive dysfunction (POCD) and neurocognitive decline (NCD). The inflammatory response to surgery may be a contributing factor. We investigated the association between inflammatory biomarkers and cognitive change up to 3 months following surgery.

Method

We recruited 70 older adults undergoing elective non‐cardiac surgery. Baseline and 3 month neurocognitive and functional assessments were performed, and delirium was assessed for 5 days following surgery. A control group of age‐similar subjects underwent assessment at similar time points. Blood was collected in 55 patients at baseline and post‐surgery at 30 min, 6h, 24h and 48h for inflammatory biomarker analysis (Tumor Necrosis Factor (TNF)‐α, Interleukin (IL)‐6, IL‐10, IL‐18). POCD was attributed if there was ≥ 1.96 SD decline in two or more neuropsychological tests compared with time‐matched controls. NCD major and mild was attributed according to DSM‐V criteria.

Result

Patients underwent a range of non‐cardiac surgical procedures and were aged 69.5 (SD 6.7)y and 48.6% were female. Mean baseline MMSE was 27.1 (7.5). Delirium was identified post‐operatively in 4% of subjects. At 3 months, 18 (32.7%) subjects had some form of cognitive decline: POCD 7%, Mild NCD 16% or Major NCD 15%. IL‐6 was significantly elevated following surgery and remained so to 48h. IL‐10 was elevated at 6h but declined to baseline by 48h. Both IL‐18 and TNF‐α were transiently lower than baseline at 30 minutes, but then returned to close to baseline levels. There was no association between inflammatory biomarker levels and delirium or cognitive change at 3 months.

Conclusion

We have confirmed the presence of new cognitive decline in a significant number of older patients up to 3 months following non‐cardiac surgery. We identified changes in inflammatory biomarkers, especially IL‐6 which was elevated for at least 48h, but no association with cognitive change. Ongoing research will address more specific biomarkers of neuronal injury.
Plasma Neurofilament Light (NfL) associated with retest learning effects on ambulatory cognitive assessments of processing speed: Results from the Einstein Aging Study (EAS)
Authors: Qin Jiyue , Wang Cuiling , Katz Mindy J. , Zetterberg Henrik , Blennow Kaj , Engeland Christopher G. , Hakun Jonathan G. , Pavlovic Jelena , Derby Carol A. , Sliwinski Martin J. , Lipton Richard B.
Published: June 2023

Background

Measurement burst designs, using ambulatory cognitive assessments facilitate the dissociation of retest effects from optimal (“asymptotic”) performance. Dissociating these features via cognitive process modeling may reveal indices of subtle cognitive impairment that signal risk for neurocognitive decline. We investigated cross‐sectional associations between plasma NfL (a biomarker of neurodegeneration), retest improvements, and optimal performance on the Symbol Match task, which assesses processing speed by response time (RT), in a racially/ethnically diverse community‐based EAS Study cohort.

Method

Analyses included 283 EAS participants free of dementia (Mean age = 77.4 years, SD = 4.8, Range = 70‐91; 67% Female; 46% Non‐Hispanic White, 40% Non‐Hispanic Black). Among them, 82 met the Jak/Bondi criteria of mild cognitive impairment (MCI). Participants completed a smartphone cognitive battery, resulting in up to 96 assessment sessions (six times per day for 16 days). Plasma NfL concentration was measured using a Single molecule array assay. A mixed‐effect negative exponential model was used to examine the associations between plasma NfL and indices of subtle cognitive impairment adjusting for covariates including age, gender, education, and race/ethnicity. Retest improvement was measured by the exponential decrease in RT across sessions and optimal performance was measured by asymptotic RT (fastest performance).

Result

On average, the RT of the Symbol Match task was 3.4 seconds (SD = 0.9). Mean plasma NfL level was 23.9 pg/mL (SD = 17.5). Higher plasma NfL levels were associated with a reduced retest improvement rate per session (estimate = ‐0.011, 95% confidence interval (‐0.013, ‐0.008) corresponding to one SD increase in plasma NfL, p<0.001). No significant association between plasma NfL and optimal cognitive performance was found. Stratified analyses showed NfL’s association with retest improvement was larger in non‐Hispanic Whites than in non‐Hispanic Blacks (‐0.009 vs ‐0.002), although formal testing of the interaction between NfL and race was not significant. Results remained very similar excluding participants with MCI.

Conclusion

Higher plasma NfL was associated with a reduced retest improvement rate on a smartphone processing speed task, highlighting its potential value for identifying subtle cognitive impairment. Longitudinal data from larger samples, a broader array of biomarkers and of ambulatory cognitive tests, are required to fully explore these issues.
Using amyloid PET as a biomarker to detect progression of early Alzheimer disease
Authors: Ali Muhammad , Mafimoghaddam Samira , Sung Yun Ju , Wang Fengxian , Fernandez Maria Victoria , Archer Derek B , Hohman Timothy J. , Satizabal Claudia L. , Yang Qiong , Beiser Alexa S. , Wang Ruiqi , Gordon Brian A. , Benzinger Tammie L.S. , Xiong Chengjie , Morris John C , Bateman Randall J. , Karch Celeste M. , McDade Eric , Goate Alison , Seshadri Sudha , Mayeux Richard , Sperling Reisa A. , Buckley Rachel F. , Properzi Michael J , Johnson Keith A. ,   Dominantly Inherited Alzheimer Network (DIAN),   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Cruchaga Carlos
Published: June 2023

Background

Alzheimer’s disease (AD), the most common form of dementia, is a complex polygenic disease with genetic, cellular, pathologic, and clinical heterogeneity. Recently, significant attempts have been made for identifying AD biomarkers for reliably tracking disease progression in its early asymptomatic stages. To this end, amyloid PET imaging has provided useful information tracking accumulation of parenchymal amyloid beta (Aβ) deposits in the brain. Previous investigations have conducted genetic association studies of CSF Aβ42, both continuously as well as using a threshold for amyloid positivity, and identified novel genes and loci potentially contributing to the preclinical stage in AD. In a recent case‐control based study using amyloid PET as a quantitative trait, Raghavan et al., identified a novel locus for amyloidosis within RBFOX1 gene in 4,314 participants, however, further investigations are needed to replicate and expand on these findings.

Method

In order to investigate the underlying genetic basis for brain amyloidosis in AD, we systematically analyzed the largest collection of amyloid imaging data (N = 6,320), across multiple ethnicities from multicenter cohorts (ADRC, A4, DIAN, ADNI, ADNIDOD, UPitt, and HABS) as a quantitative trait to identify the functional variants and genes driving the association of AD. Furthermore, we have conducted diagnosis‐, gender‐, and APOE‐stratified analyses to investigate the effect of these variables on the brain amyloidosis.

Result

Preliminary results found a strong APOE signal in chr19 (min P = 1e‐185) and a genome‐wide significant hit (P = 2e‐08) in the chromosome 7 (potentially, associated to TMEM106B gene) warranting further investigation (Fig. 1). Moreover, some suggestive signals were detected in chr10 (P = 1e‐07) and chr12 (P = 5e‐07). Consistent with previous finding, we found RBFOX1 to be associated with increased amyloid burden (β = 0.07), however, the signal was only nominally significant (P = 0.03). Additional analyses including multi‐ancestry meta‐analysis using FHS, AIBL, and EISAI cohorts and post‐GWAS analyses are ongoing.

Conclusion

The identification of pre‐clinical AD‐specific molecular signatures and pathways will enable the characterization of appropriate therapeutic targets for the prevention and/or treatment of AD. Results generated from our investigation will further serve to generate prediction models for amyloid positivity and Mendelian Randomization (MR) analyses.
Divergent patterns of cognitive deficits and structural brain alterations between older adults in mixed‐sex and same‐sex relationships
Authors: Manca Riccardo , Correro Anthony N , Gauthreaux Kathryn , Flatt Jason D.
Published: June 2023

Background

Sexual minority (SM) or lesbian, gay, bisexual, and queer older adults experience health disparities that may cause cognitive decline. Several studies have reported higher rates of subjective cognitive complaints in SM older adults, but evidence of increased cognitive decline has been inconsistent. One study found that older adults with Alzheimer’s disease (AD) in same‐sex relationships (SSR), compared to mixed‐sex relationships (MSR), had more severe neuropsychiatric symptoms associated with atrophy in fronto‐temporal regions. We sought to compare behavioral and structural brain parameters of SSR and MSR older adults and evaluate their impact on cognitive performance.

Method

National Alzheimer’s Coordinating Center data were selected according to the following inclusion criteria: 55+ years of age, presence of a co‐participant, and availability of brain volume and mean thickness data. Clinical Dementia Rating® (CDR®) scores were used to assign participants to cognitively impaired (CI; CDR®≥0.5) or cognitively unimpaired (CU; CDR®<0.5) groups. We identified 1076 MSR (583 CU) and 38 SSR (25 CU) participants with Mini‐Mental State Exam (MMSE) and Neuropsychiatric Inventory Questionnaire (NPI‐Q) data within six months of a study visit. Comprehensive neuropsychological test results were available for a sub‐sample of participants (940 MSR and 33 SSR). General linear models were used to investigate the effects of diagnosis, relationship, and NPI‐Q scores on structural and cognitive outcomes.

Result

The MSR group presented with more impairments. Diagnosis‐by‐relationship interaction effects were observed for brain parameters: 1) CI‐MSR had more atrophy in occipital, medio‐temporal, and frontal areas; 2) CU‐MSR had reduced volume/thickness in orbito‐frontal, insular, and anterior cingulate cortices. The MSR groups had greater executive, memory, and language deficits. Neuropsychiatric symptom severity was negatively associated with volume and thickness of bilateral temporo‐cingulate areas and total MMSE scores in the MSR groups only.

Conclusion

MSR older adults had greater cognitive and behavioral impairments compared to SSR older adults. CI‐MSR had greater grey matter atrophy in areas particularly affected by AD (i.e., medio‐temporal regions). Our results suggest that SM older adults may present with less neurocognitive impairment on comprehensive assessment, despite previous evidence of subjective complaints. Further investigations are needed to clarify factors influencing cognitive decline in older SM.
In the context of a deprived neighborhood, does self‐identified race cause dementia?
Authors: Zhang Xiao , Chang Chung‐Chou H , Ganguli Mary
Published: June 2023

Background

Although accumulating evidence has shown that individual socioeconomic status affects dementia incidence, it remains unknown whether a higher degree of neighborhood disadvantage which is independent of individual socioeconomic status contributes to the excess risk of dementia among African Americans (AA).

Method

In the Monongahela‐Youghiogheny Healthy Aging Team and 15104 Senior Project, two population‐based prospective cohort studies in an economically disadvantaged Rust Belt community, 2733 participants aged 65+ years were assessed for their health history, lifestyle, and cognitive functioning. Mild cognitive impairment (MCI) or dementia was defined as Clinical Dementia Rating score ≥0.5. Each participant was assigned an Area Deprivation Index (ADI) value according to the census block group where one resided, indicating the level of neighborhood disadvantage. In cross‐sectional data, racial differences in the odds of MCI or dementia were assessed using weighted logistic regressions. Inverse probability weighting was used to balance AA and European Americans (EA) with respect to 1) ADI, 2) other confounders (age, sex, APOE*4 genotype, cardiometabolic diseases, individual socioeconomic status, health‐related behaviors, use of regular health services, functional health literacy, and air pollution [PM2.5]), and 3) ADI and other confounders.

Result

The frequency of MCI and dementia were 648 (24%) and 25 (0.9%), respectively. AA had significantly higher proportion of MCI or dementia (35% vs. 24%, p = 0.001) and higher mean ADI (96 vs. 79, p<0.0001) than EA. Being AA was associated with higher odds of MCI or dementia compared to being EA (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.26 ‐ 2.33, unadjusted model). After balancing racial groups with respect to ADI only, the difference between AA and EA no longer reached the level of significance. When balancing all other confounders only, the OR was 1.66 (95% CI = 1.04 ‐ 2.67) and the confounders explained 5.2% of the observed disparity. After balancing both ADI and other confounders, the difference again became non‐significant (OR = 1.61, 95% CI = 0.93 ‐ 2.80) and resulted in 11.1% of the MCI or dementia disparity being explained.

Conclusion

A higher degree of neighborhood disadvantage may contribute to the excess risk of MCI or dementia found among AA.
The UC Davis ADRC Cohort Study aimed to use established marketing techniques to recruit African Americans to participate in research and increase the center’s social media presence
Authors: Johnson David K , Walker Aliyah N
Published: June 2023

Background

The UC Davis ADRC Cohort Study aimed to use established marketing techniques to recruit African Americans to participate in research and increase the center’s social media presence. African American’s have been historically excluded from research at the same time they are disproportionately impacted by Alzheimer’s Disease. Current recruitment best practices for engaging underrepresented groups in research includes community outreach events, flyers, and recruitment in academic or clinical settings. Contemporary social media marketing methods allow us to reach very specific demographics, which can be helpful to find and recruit groups typically underrepresented in research

Method

We hired a marketing firm to run a market analysis to identify what our target audience looked like. We developed ad content with people’s motivations for participating in mind. The ads included Alzheimer’s disease awareness, testimonial interviews from research participants, information on the center, or education on dementia. The campaign was a combination of ads through Facebook, google ads, twitter, Instagram, and yahoo ads. We supplemented our advertising with Facebook posts on the ADRC page to create a buzz of conversation around the videos. The ads when clicked on let to the ADC website, YouTube channel, Facebook page, or Study pages where people could sign up to be contacted for recruitment.

Result

Because of the campaign, our ADRC Facebook followers increased by 8%. The data on the participant recruitment funnel was 102 clicks to visit the ADRC recruitment webpage from Facebook Ads; 27 people signed up via study page; 7 were ineligible (usually no study partner); 6 were information seekers (adult children or <65yrs); and 13 were enrolled. The 13 participants completed all study visits that year. This direct marketing campaign netted over half of the annual 20 replacement volunteers needed by the intensive ADRC cohort study that usually takes a full‐time staff person 6‐8 months to recruit. By comparison, direct marketing/recruitment was incredibly efficient.

Conclusion

Research centers may benefit from integrating common marketing methods for recruitment of underrepresented groups. There were some difficulties implementing the marketing plan with the IRB and research Center model. More research can be done to evaluate effective strategies for recruiting diverse participants.
A multivariable mendelian randomisation study of serum lipids and dementia risk within the UK Biobank
Authors: Pham Kitty , Mulugeta Anwar , Lumsden Amanda , Hyppönen Elina
Published: June 2023

Background

An unfavourable lipid profile has been associated with the increased risk of dementia or Alzheimer’s disease in both observational and genetic studies1,2. However, it is challenging to investigate each serum lipid measure individually due to the high correlation between the lipid traits. We aimed to discover causal associations between genetically instrumented serum lipid measures (low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), triglycerides, apolipoprotein‐A1 (apoA) and apolipoprotein‐B (apoB)) and the risk of dementia.

Method

We conducted multivariable and univariable Mendelian randomisation (MR) analyses on 329,896 UK Biobank participants (age 37‐73 years) to examine the associations between each serum lipid measure and the risk of dementia. The multivariable approach allows us to assess the association of each lipid measure with the outcome, in cases where the genetic variants used to estimate the exposures are mediated by one another.

Result

In the univariable MR analyses, we found that genetically determined higher LDL‐C and apoB were both associated with increased risk of dementia, while higher HDL‐C and apoA were associated with decreased risk of dementia. Meanwhile, using multivariable MR analyses, in a model containing LDL‐C, triglycerides and apoB, only apoB remained significantly associated with increased risk of dementia.

Conclusion

Our findings suggests that when considering the correlation between lipid measures, apoB plays an important role in the previously reported association between serum lipids and increased risk of dementia.

References:

1Iwagami, M, Qizilbash, N, Gregson, J, Douglas, I, Johnson, M, Pearce, N, Evans, S & Pocock, S 2021, 'Blood cholesterol and risk of dementia in more than 1·8 million people over two decades: a retrospective cohort study', The Lancet Healthy Longevity, vol. 2, no. 8, pp. e498‐e506.

2Zhang, X, Tian, Q, Liu, D, Geng, T, Ge, S, Zheng, D, Wu, L, Song, M, Hou, H, Wang, W & Wang, Y 2020, ‘Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta‐analysis’, Transl Psychiatry, vol. 10, no. 145, https://doi.org/10.1038/s41398‐020‐0822‐x.
Feasibility analysis of the design of a psychosocial intervention in dementia: Sensitivity analysis
Authors: Rabaneda‐Bueno Rubén , López‐Ortega Mariana , Guzman Azucena , Robledo Luis Miguel Gutierrez , Torres‐Castro Sara
Published: June 2023

Background

A multicomponent staff training intervention was conducted to improve residential dementia care. The purpose of this work is to present the simulation of the effectiveness of the intervention design over time.

Method

Pilot study with mixed methods, two‐arm randomized controlled clinical outcomes in 7 care homes in Mexico City. Staff outcome measures were: Maslach Burnout Inventory (MBI); Approaches to Dementia Questionnaire (ADQ); Sense of Competence in Dementia Care Staff (SCIDS). Residents' outcome measures were: Quality of Life‐Alzheimer’s Disease scale (QoL‐AD) and Neuropsychiatric Inventory‐Nursing Home Version (NPI‐NH). Using the functions of the R package powerlmm, we performed computer simulations based on linear changes over a period of up to 24 weeks. The measurements were divided into three time points corresponding to the schedule of our study (baseline, post‐intervention and follow‐up). In the different trials, we specified different numbers of subjects and group sizes, including those in the present study, always considering an unbalanced cluster design. We also considered the dropout rate of participants, which in this study was almost 30% and focused on the post‐intervention period, with no additional dropouts at follow‐up. We conducted simulations to determine the performance of our longitudinal study design with fewer or no unanticipated dropouts.

Result

55 residents and 126 staff participants were recruited in seven care homes. We found that the highest power was achieved for MBI: Personal fulfillment and SCIDS: Sustaining personhood, which were the only variables with a significant effect for the Time × Treatment interaction in the model inference. Focusing on the first of these variables and assuming the specific values for each input parameter, we see that our study design with 7 care homes was potentially capable of detecting a significant effect size of the growth effects of the intervention. Thus, the estimated sample size for a power of 80% would be nearly 85 participants, which corresponds to the complete data (i.e., no dropouts), and about 138 participants for a power of 90%.

Conclusion

A higher level design that includes more care homes would be sufficient to achieve effective estimates above the 80% threshold while maintaining the lowest number of participants.