bluuebunny/crossref_metadata_2025 huggingface dataset:
The technological reserve hypothesis: A meta‐analysis
Authors: Benge Jared , Scullin Michael K
Published: December 2023

Background

Older adults are increasingly crossing the digital divide, regularly engaging with technologies such as the internet, smartphones, and personal computers. Two distinct theories of the cognitive impact of this digital engagement have been raised. According to the digital distraction hypothesis, regular engagement with technology acutely negatively effects cognition by increasing distractions and decreases cognitive skills over the long‐term by regularly offloading tasks such as recall of facts, directions, and other daily memory tasks into digital technologies. By contrast, according to the technological reserve hypothesis, regular engagement with technology acutely benefits functioning via use of assistive technologies and can reduce long‐term risk for cognitive disorders with age by promoting complex cognitive engagement, sustained connection, and acquisition of digital based compensatory skills.

Method

Random effects meta‐analysis was used to pool effect sizes, with primary effect sizes reported as odds ratios (odds of developing a cognitive diagnosis or odds of having lower cognitive scores as appropriate to each study). We conducted systematic evaluations of study quality and to determine the influence of socioeconomic, education, age, and type of technology.

Result

Of 6,183 records identified, 26 studies met inclusion criteria and were included in the final analysis. Engagement with smartphones, computers, and/or the internet was associated with decreased risk of cognitive decline, mild cognitive impairment, and dementia (pooled OR = 0.45, 95% CI 0.318‐0.637, p<.0001; I2 = 99.2%; Figure 1). Potential confounding variables, such as adjustment for socioeconomic factors and education or type of technology measured did not moderate this relationship (Figure 2). Study quality was generally good (Figure 3), though all studies assessed technology use by self‐report and few measured intraindividual changes in technology use over time.

Conclusion

Engagement with everyday digital technologies is associated with decreased risk of cognitive decline and dementia, consistent with the technological reserve hypothesis. While these studies do not prove causality of this relationship, they do highlight the potential for digital health approaches to promote cognitive health and well being with age. Limitations, particularly with regard to understanding digital disparities and incorporating objective digital use metrics in future studies are discussed in detail.
Impact of hs‐CRP concentration on brain structure alterations and cognitive trajectory in Alzheimer’s disease
Authors: Zhang Ye
Published: December 2023

Background

This study investigated hs‐CRP concentration, brain structural alterations, and cognitive function in the context of AD (subjective cognitive decline [SCD], mild cognitive impairment [MCI], and AD).

Method

We retrospectively included 313 patients (mean age = 76.40 years; 59 with SCD, 101 with MCI, and 153 with AD) for a cross‐sectional analysis and 91 patients (mean age = 75.83 years; 12 with SCD, 43 with MCI, 36 with AD) in the longitudinal analysis. Multivariable linear regression analysis was conducted to investigate the relationship between hs‐CRP concentration, brain structural alterations, and cognitive function.

Result

In patients with SCD, hs‐CRP was inversely associated with gray matter volumes (GMVs) in the left supramarginal gyrus (pFDR = 0.044, 𝛽 = ‐0.22), and positively associated with GMVs in left lateral occipital gyrus (pFDR = 0.009, 𝛽 = 0.34) and left rostral middle frontal gyrus (pFDR = 0.038, 𝛽 = 0.29). In patients with AD, hs‐CRP was positively associated with GMVs in the left fusiform gyrus (pFDR = 0.017, 𝛽 = 0.22) and left inferior temporal gyrus (pFDR = 0.043, 𝛽 = 0.17). According to the longitudinal analysis, the interaction of diagnosis and hs‐CRP was associated with annual cognitive changes. Among these patients with AD, lower baseline hs‐CRP was correlated with greater future cognitive decline (r = ‐0.41, p = 0.0127).

Conclusion

Our study suggest that hs‐CRP may differentially affect the neuropathology of different stages of AD. For patients diagnosed with AD, elevated CRP level may be protective on brain structure alterations and future cognitive changes.
Latent Profile Analysis of Healthy Lifestyle Behaviors and its’ Association with Cognitive Decline in Older Adults
Authors: Halloway Shannon , Wagner Maude , Tangney Christy C , Lange‐Maia Brittney S , Bennett David A. A , Arvanitakis Zoe , Schoeny Michael E
Published: December 2023

Background

Lifestyle health behaviors, such as physical activity, cognitive activity, healthy diet, and social engagement, can improve cognition in older adults. We aim to identify profiles of late‐life lifestyle health behaviors related to subsequent maintenance of cognition and explore sociodemographics and health characteristics as effect modifiers.

Method

Analyses were conducted using data from 715 older adult participants from the Rush Memory and Aging Project who were dementia‐free at the first concurrent assessment of self‐reported lifestyle health behaviors (physical activity, cognitive activity, dietary habits, and social engagement) and with ³2 annual cognitive tests to assess changes in cognition. Neuropsychological test scores were grouped to form summary measures of global cognition, and five domains (episodic memory, semantic memory, working memory, perceptual speed, visuospatial memory). First, each participant was assigned to a specific group based on the initial levels of lifestyle behaviors using a latent profile analysis. Then, we assessed change in cognition among groups using linear mixed‐effects models adjusted for sex, education, and age at baseline. In additional models, we examined potential effect modifiers, including motor function, vascular risk factors (hypertension, diabetes, smoking), and vascular diseases (stroke, cardiac disease, congestive heart failure, claudication).

Result

Three groups were identified: high engagement in behaviors (n = 183), moderate engagement (n = 441), and low engagement (n = 91). Participants in the high group were more likely to be women, younger, and with higher educational level, compared to the low group. Compared to the high group, the low group had a faster annual rate of decline in global cognition (mean difference [MD] = ‐0.06 [‐0.08;‐0.03], p<.0001) after full adjustment. In addition, compared to the high group, the low group showed a faster rate of decline in episodic memory, semantic memory, and perceptual speed, while the moderate group had a faster rate of decline for episodic memory only. There were no significant effects modifiers by any sociodemographic, motor function, or vascular health factor.

Conclusion

Classification in the moderate or high engagement group was related to better maintenance of cognition over time. Future research should examine multidomain intervention strategies that promote adoption of higher engagement in health behaviors targeting at least moderate levels.
Myeloid Differentiation Factor 2 Inhibition Protects Against Doxorubicin‐induced Microglial Activation and Senescence
Authors: Oo Thura Tun , Liang Guang , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: December 2023

Background

Doxorubicin, an anti‐tumor drug, generates neuroinflammation that leads to microglial senescence and chemo‐brain (1, 2). Toll‐like receptor 4 (TLR4) signaling pathway is mainly expressed in microglia and it plays a key role in developing doxorubicin‐induced neuroinflammation, microglial activation and chemo‐brain (3). Myeloid differentiation factor 2 (MD‐2) is known as an essential protein in activation of TLR4 signaling pathway (1). However, the effect of blocking TLR4 signaling via targeting MD‐2 on doxorubicin‐induced microglial activation and senescence has never been investigated.

Method

The human microglial clone 3 cell line (HMC3) was treated with three different doses of MD‐2 inhibitor (L6H21: 5μM, 10μM, 20μM) for 30 minutes, then with doxorubicin hydrochloride (DOX) (50nM) for 24 hours. After 24 hours treatment with L6H21 and DOX, the microglial cells were assessed for the TLR4 signaling, microglial activation, cell death and cellular senescence pathways.

Result

DOX treatment activated TLR4 signaling pathway as well as microglia, as evidenced by significantly increased protein expressions of TLR4, MD‐2, tumor necrosis factor alpha and ionized calcium‐binding adapter molecule 1. In addition, DOX treatment induced microglial cell death and senescence, as shown by significantly increased protein expressions of Bcl‐2 associated X‐protein to B‐cell lymphoma 2 ratio and p16Ink4a. Treatment with L6H21 (5μM) attenuated not only TLR4 signaling along with microglial activation, but also apoptosis and cellular senescence in DOX‐treated microglia. L6H21 (10μM and 20μM) protected against TLR4 signaling along with microglial activation, apoptosis as well as cellular senescence in DOX‐treated microglia.

Conclusion

These findings imply that MD‐2 inhibition could be the potential therapeutic strategy for attenuating DOX‐induced microglial activation and senescence.

References

1. Oo TT, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. Emerging roles of toll‐like receptor 4 in chemotherapy‐induced neurotoxicity. NeuroToxicology. 2022;93:112‐27.

2. Marques L, Johnson AA, Stolzing A. Doxorubicin generates senescent microglia that exhibit altered proteomes, higher levels of cytokine secretion, and a decreased ability to internalize amyloid β. Experimental Cell Research. 2020;395(2):112203.

3. Ongnok B, Maneechote C, Chunchai T, Pantiya P, Arunsak B, Nawara W, et al. Modulation of mitochondrial dynamics rescues cognitive function in rats with ‘doxorubicin‐induced chemobrain’ via mitigation of mitochondrial dysfunction and neuroinflammation. Febs j. 2022;289(20):6435‐55.
Bridging the Brain‐Age Gap: Quantifying regional contributions using Shapley‐Owen values
Authors: Sinha Harsh , Raamana Pradeep Reddy
Published: December 2023

Background

The concept of brain age gap (BAG) is increasingly being used to express the deviation of brain from the normative trajectory. However, each brain region is subject to independent aging transformations due to differences in neurobiological processes. So, reducing high‐dimensional imaging features down to a single number for simultaneously evaluating brain health, capacity, and residual lifespan is an error‐prone task. Furthermore, brain age is observed to be correlated with chronological age. Therefore, there is need for a systematic empirical evaluation of BAG to understand contributions of different regions when considering BAG as a potential aging biomarker for age‐related neuroanatomical abnormalities. Although methods such as saliency maps have been proposed, there is need for a model‐agnostic technique that quantifies consistent feature contributions across various predictive models.

Method

We used morphological features estimated by Freesurfer from T1w (OASIS3 dataset) to train predictive models for BAG. The bias‐correction was performed using two strategies (i.e., scale‐down and scale up) on each of linear regression and XGBoost models as shown in Figure 1. We present feature importance for top‐10 features (based on median feature importance scores) across 100 bootstrap runs (Figures 2 and 3 respectively), along with correlations with chronological age. We use Shapley‐Owen feature attribution technique as a way of assigning importance to features.

Result

As shown in Figures 2 and 3, we found sub‐cortical, anterior cingulate, and ventricle volumes among the most relevant features. We also observe that SHAP determines an almost identical set of most relevant features for predicting corrected BAG irrespective of the predictive model (linear regression or XGboost) or the bias‐correction approach. Furthermore, we found the results to be consistent with prior literature e.g., subcortical brain volumes esp. gray matter. We also empirically observe that bias‐correction mitigates dependence on chronological age.

Conclusion

We present a systematic empirical evaluation to identify the most relevant morphological features for predicting corrected BAG using SHAP. A consistent overlap of most relevant features irrespective of predictive model and the bias‐correction approach provides evidence for the robustness of using Shapley‐Owen values in explaining the contribution of morphological features for predicting corrected BAG.
Most caregivers who choose tube feeding for a relative with advanced dementia don’t want it for themselves
Authors: Cheng ‐ Heng Li , Cheong Chin Yee , Tay Poh Peng , Yap Philip Lin Kiat , Malhotra Chetna
Published: December 2023

Background

Although long‐term enteral feeding in advanced dementia is not advocated, a significant proportion of people with severe dementia (PWSDs) receive nasogastric tube (NGT) feeding. Often, in the absence of advanced care planning by the PWSDs, their caregivers may need to make pivotal decisions on the issue. Hence, we assessed perceptions of caregivers of PWSDs regarding NGT feeding and the association between caregiver factors and NGT feeding

Method

Community‐dwelling PWSDs with a FAST 6c score or higher, were recruited as part of the PISCES study, a prospective longitudinal cohort study. Their informal primary caregivers (family members in regular contact with the PWSDs and involved in main decision‐making process) were surveyed.

Result

215 caregivers of PWSDs enrolled in the study, of which 9.8% (n = 21) utilised NGT for their PWSD. Most (90.5%) caregivers of PWSDs receiving NGT reported that they understood the risks and benefits of NGT; most (85.8%) also agreed with the decision for NGT and reported that they believed it would allow the PWSD to live longer (85.7%). However, only 28.6% of caregivers wanted to be tube‐fed themselves if positions were reversed and 52.4% felt that tube feeding had reduced PWSDs’ quality of life. Comparing caregivers of PWSDs with and without NGT, there was no significant difference in their understanding of the natural course of dementia with only half of each group acknowledging that dementia can cause death (NGT 57.1% vs non‐NGT 56.1%, p = 0.969), nor difference in their knowledge of the PWSDs’ prognosis with majority indicating that they did not know how long the PWSD would live (NGT 85.7% vs non‐NGT 90.7%, p = 0.337). There was also no significant difference in their goals of care for the PWSDs with comfort reported as the primary goal for both groups (NGT 90.5% vs non‐NGT 92.3%, p = 0.773).

Conclusion

There is a dissonance between caregivers’ self‐reported understanding and support of NGT use, and their preferences for NGT themselves, its perceived effect on PWSDs’ quality of life and goals of care. Further in‐depth qualitative exploration of the reasons underlying this discordance can provide more clarity on the issue.
Violence against elderly people with Dementia
Authors: Santos Lucas Neves , Alves Larissa Scoralich , Lourenço Lelio Moura
Published: December 2023

Background

With the fast aging of the world population, dementia has been one of the most prevalent diseases in older people, and quality dementia care is needed for a slow progression of the disease. Good practices are important on this topic, since the illness is extremely complicated to handle, being stressful and frustrating. Hence, it is important to know some actions and behaviors should be avoided, specially forms of violence against older people with dementia.

Method

We conducted a search of published research that presented the descriptors “violence” and “dementia” in their title. We also reviewed the summaries and sought for the theme “violence suffered by elderly people with dementia”. We searched four databases from inception to search date (December 2022), extracted data and conducted a narrative synthesis of evidence. Several studies were found, and we included based on the relevance for this review.

Result

Most of the studies found in the scientific literature are focused on the violence made by people with dementia, and not the violence suffered by them, which is the focus of this review. In the studies used for this review, the characteristics of victims are listed as quiet, self‐effacing, with limited interpersonal coping skills, and excessive denial. In most studies, those who commit violence are men, caregivers, spousal and other family members. The most common types of violence are domestic, psychological, physical, verbal and negligence. The victims tend to remain in the abusive household because of many factors such as economic dependence, fear of major violence and children.

Conclusion

There is a need for more studies focused on the violence suffered by elderly people with dementia in addition to a better detailing of factors such as gender, risk factors and how to prevent the violence. Family, caregivers and health professionals need to be attentive to some of the possible warning signs of abuse such as fractures and bruises that are not easily explained, chronic pain, post‐traumatic stress disorder, nightmares and other relevant situations that may alert to elderly abuse.
Short‐term high‐fat diet feeding induces cognitive decline, aggressiveness and anxiety‐like behavior in adult zebrafish (Danio rerio)
Authors: Picolo Victor Luna , Bem Andreza Fabro
Published: December 2023

Background

Obesity is a high‐ prevalence (13% of adult population in 2016), global health concern defined by a high body mass index (BMI). Several comorbidities are associated, including some affecting central nervous system (CNS), i.e. neurodegenerative diseases, cognitive deficit and psychobehavioral disturbs.

Method

Zebrafish has raised as a versatile and cheap model widely used to study human diseases, including obesity and neurological diseases. Therefore, our objective is verify the impact of a high‐fat diet on the central nervous system (CNS) using well‐ stablished behavioral tests. Animals was feed according with three dietary groups. The standard diet group (SD) received only 7.5 mg/fish of dry food, while the high‐fat diet groups received 5 mg/fish dry food plus 7.5 (HFD‐7.5) or 15 mg/fish (HFD‐15) of chicken egg yolk. Dietary fat content (w/w) was approximately 6.5%, 16.9% and 21.1%, respectively. After two weeks of diets ingestion, behaviors were assessed.

Result

Both HFD groups had obesogenic effects, indicated by increase on BMI, abdominal length and body weight compared with SD group. We show a HFD ingestion induced aggressive and anxiety‐like behavior on zebrafish, as measured by mirror‐induced aggression and novel tank diving test, respectively. Also, the higher concentration of HFD (HFD‐15) elicited cognitive deficit on inhibitory avoidance test while sociability was unaffected, as determined by the social preference test.

Conclusion

Our results are in accordance with evidences in obese human and rodent models, suggesting similar effects of fat intake. Therefore, we highlight the unexplored potential of zebrafish to elucidate this study field.
Virtual Reality Companion for Dementia Patients in Long‐term Care: A Feasibility Study
Authors: Frank Andrew R , Sheehy Lisa
Published: December 2023

Background

Persons with dementia (PWDs) develop progressive cognitive and physical decline which often results in placement in long‐term care (LTC). Within LTC, PWDs are at high risk for social isolation, as friends and family members may not visit often, a problem exacerbated by the COVID‐19 pandemic.

Method

This project is developing a novel application for immersive virtual reality (VR), in which an avatar (i.e. a visual representation of a person) acts as an autonomous artificial companion for PWDs in LTC. This avatar is programmed to listen to PWDs through microphones embedded in VR goggles, and provide verbal interaction with PWDs through embedded speakers. In this way, the avatar can provide a source of conversation and socialization, available at any time, for any duration. This engagement may improve quality of life, and reduce responsive and reactive dementia behaviours.

Result

Our virtual companion was trialed in 10 PWD (3 men; 7 women). Most PWD found the companion to be engaging, and this invited positive reminiscence in 3 PWD. VR goggles were generally well‐tolerated, though 2 PWD closed their eyes and/or did not respond. The ability to interact verbally in a conversational manner was easier in patients with milder dementia. There was some poor performance of the speech recognition software, which impacted the flow of the conversation. Significant verbal feedback was recorded on how to improve the avatar, and how to enhance the conversation.

Conclusion

An autonomous artificial companion presented in virtual reality (VR) is feasible, and may benefit persons with dementia who are at risk of social isolation. Future iterations will incorporate improved speech recognition and artificial intelligence (AI)‐guided conversation generator software.
Abnormal Phosphorylation at Ser293 promotes the Oligomerization of Tau Repeat R2: A Computational Study
Authors: Man Viet H
Published: December 2023

Background

In tauopathies such as Alzheimer’s disease (AD), aberrant phosphorylation causes the dissociation of tau protein from microtubules. The dissociated tau then aggregates into sequent forms from soluble oligomers to paired helical filaments (PHF), and insoluble neurofibrillary tangles (NFTs). NFTs is a hallmark of AD, while oligomers are found to be the most toxic form of the tau aggregates. Therefore, understanding tau oligomerization with regard of abnormal phosphorylation is important to therapeutic development of AD. In this study, we investigated the impact of phosphorylated Ser293, one of 40 aberrant phosphorylation sites of full‐length tau protein, on monomeric and dimeric structures of tau repeat R2 peptides

Method

Wild‐type tau repeat R2 (wtR2) was taken from an experimental structure of R2‐microtubule complex (PDB code 6CVN). The phosphorylated Ser293 R2 peptide (pS293R2) was obtained by phosphorylating the wtR2 at Ser293 residue. Extensive replica exchange molecular dynamics simulations using all‐atom force field and explicit solvent were carried out for five systems including two monomers (wtR2 and pS293R2) and three dimers (wtR2+wtR2, wtR2+pS293R2, and pS293R2+ pS293R2). The structures of R2 monomers and dimers sampled by the simulations were characterized and compared.

Result

For monomeric conformations, the phosphorylation enhances intramolecular interaction, compactness and β content. For dimeric cases, the phosphorylation increases intermolecular interaction, β‐sheet formation, and turn‐coil structural transition. Interestingly, the phosphorylated residue strongly interacts with cations, resulting in a pS293‐cation‐pS293 bridge in pS293R2+ pS293R2 system.

Conclusion

Our results suggest that abnormal phosphorylation at Ser293 accelerates the oligomerization of R2 peptides, and consequently it may promote tau aggregation. Furthermore, we also found a pS293‐cation‐pS293 bridge formed, thus uncovered the essential role of cation ions in the oligomerization of the phosphorylated R2 repeat. Our findings suggest that phosphorylation at Ser293 should be taken into consideration when screening the inhibitors of tau oligomerization.
Plasma phosphorylated tau 181 and modifiable risk factors for dementia in a large scale cohort of Australian older adults
Authors: Roccati Eddy , Collins Jessica M , Bindoff Aidan D , Alty Jane E , Bartlett Larissa , King Anna E , Vickers James C
Published: December 2023

Background

Up to 40% of dementia cases could be prevented by addressing modifiable risk factors. Alzheimer’s disease (AD), the most common form of dementia, is preceded by up to decades of silent pathological change providing an ideal window for early detection and intervention. In this study, our objective was to examine the associations between modifiable risk factors and plasma phosphorylated p‐tau 181, a hallmark biomarker of early AD.

Method

Participants were recruited from the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND), a prospective public health initiative in Tasmania, Australia’s southernmost island state. ISLAND participants were invited to complete a set of surveys online: a questionnaire on dementia risk factor adherence, demographic surveys and cognitive tests via the Cambridge Neuropsychological Test Automated Battery (CANTAB); Paired Associates Learning (PAL) and Spatial Working Memory (SWM). At four clinics across the state, participants also provided blood samples for measurement of plasma phosphorylated p‐tau 181 and genotyping for APOE.

Result

A total of 738 participants (mean age 65.41 years, mean education 17.36 years, 71.8% female, 26.4% ε4+) took part in the study. We found gender‐specific effects on cognition, whereby identifying as male was associated with significantly lower learning ability (PAL) whilst identifying as female was associated with significantly lower executive function (SWM). In multivariate linear models, increasing alcohol consumption (measured in standard drinks per week) was significantly associated with lower plasma p‐tau 181. In adjusted models, no other modifiable risk factors examined were associated with p‐tau 181. Increasing age, identifying as male and possessing at least one APOE ε4 allele were all associated with higher plasma concentrations of p‐tau 181

Conclusion

Higher alcohol consumption, higher age, identifying as male and having an APOE ε4 allele were all associated with lower plasma phosphorylated tau 181. This contributes to evidence that both modifiable and non‐modifiable dementia risk factors are related to the biological precedents of AD. These associations were related to gender and genetics, therefore a panel of modifiable and non‐modifiable variables should be included in screening or diagnostic testing for pre‐clinical AD. More research is needed regarding specific alcohol types and biomarkers of AD.
Aging and Alzheimer’s Disease Have Dissociable Effects on Local and Regional Medial Temporal Lobe Connectivity
Authors: Hrybouski Stanislau , Das Sandhitsu R. , Xie Long , Wisse Laura EM , Kelley Melissa , Lane Jacqueline , Sherin Monica , DiCalogero Michael , Nasrallah Ilya M. , Detre John A. , Yushkevich Paul A. , Wolk David A.
Published: December 2023

Background

The extent to which pathological processes in aging and Alzheimer’s disease (AD) relate to functional disruption of the medial temporal lobe (MTL)‐dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity (FC) alterations between anterior and posterior regions of the MTL and in MTL‐associated functional communities – the Anterior‐Temporal (AT) and Posterior‐Medial (PM) networks – in normal agers, individuals with preclinical AD, and patients with Mild Cognitive Impairment or mild dementia due to AD.

Method

In this cross‐sectional study, we analyzed data from 179 individuals from the Aging Brain Cohort study of the Penn ADRC. Detailed information about participants is provided in Table 1. For intra‐MTL FC comparisons, the MTL subregions were segmented using the automated segmentation of hippocampal subfields‐T1 (ASHS‐T1) pipeline (Fig. 1a). When modeling the MTL’s interactions with the rest of the cortex, we employed four MTL ROIs (left/right × anterior/posterior) derived from an ex vivo atlas of tau accumulation in the MTL. Our functional datasets were preprocessed using a customized fMRIprep pipeline. Sparse network estimations and modularity‐based consensus clustering were used to reconstruct the AT and PM network systems (Fig. 1b). Age effect analyses and group comparisons along the AD continuum were performed using the General Linear Model within the network‐based statistical framework.

Results

The preclinical stage of AD was characterized by increased FC between the perirhinal cortex and other regions of the MTL, as well as between the anterior MTL and its direct neighbors in the AT network (Fig. 1c‐d). This effect was not present in symptomatic AD. Instead, symptomatic patients displayed reduced hippocampal and intra‐PM connectivity. For normal aging, our results led to three main conclusions (for visuals, see Fig. 2). First, intra‐network connectivity of both the AT and PM networks decreases with age. Second, FC between the anterior and posterior segments of the MTL declines with age. Finally, within the MTL, we observed greater vulnerability of the posterior MTL subregions, particularly the parahippocampal cortex, to age‐associated FC decline.

Conclusion

Together, the current results provide evidence for aberrant connectivity in the preclinical stage of AD that may have implications for early AD pathophysiology.
Caregivers journey through experiences of people living with dementia and history of wandering behaviour
Authors: N Anu K , Thirumoorthy A , Antony Sojan , Vasanthra Cicil R , Issac Thomas Gregor , Sivakumar Palanimuthu Thangaraju
Published: December 2023

Introduction

Wandering is one of the major behavioural symptoms of dementia. It leads to the high level of caregiver burden. Understanding the caregivers’ difficulties and management strategies will help the mental health professionals to gain knowledge on feasible care techniques in India.

Aim

Aim of this study was to explore the experience of caregivers in the management of wandering among persons with dementia.

Methodology

Three case studies were selected from the family caregiver population and who reported wandering behaviour and associated distress. Interview method was used to understand the experience of caregivers.

Results

All caregivers used supervision and locking the doors of their houses as key strategies to prevent the wandering behaviour among the persons with dementia. Other prominent strategies were seeking community support and listing out the destinations in which the person is found commonly. Keeping an identity card, planned activities of daily living, restricted movement, safety planning and division of caregiving responsibility were also applied in management of wandering by family caregivers.

Conclusion

Early identification of wandering behaviour and caregiver education can prevent the frequency of wandering and the associated burden. Low‐middle‐income countries are yet to develop a comprehensive case management services for the families affected by the wandering secondary to dementia.
Reducing Risk of ADRDs: Innovative Framework to Inform Behavior Change
Authors: Kurzman Alissa , Londono Mary , Truong Vivian , Morales‐Haro Omar , Lam Amy , Kaleem Hiba , Ritt‐Olson Anamara , Boden‐Albala Bernadette
Published: December 2023

Background

In the United States alone, more than six million individuals are living with Alzheimer’s disease and related dementias (ADRDs), with minority groups disproportionately impacted. An estimated one‐third of ADRD cases is associated with eight modifiable risk factors: physical inactivity, smoking, depression, low education, diabetes, midlife obesity, midlife hypertension, and hearing loss. With the ADRD pandemic fast approaching, there is greater urgency to identify and adopt risk reduction behavior changes. Lifestyle interventions have shown efficacy in reducing risk for ADRDs and delaying the onset of symptoms. These interventions are often grounded in traditional theories of health behavior change; however, few intervention frameworks exist that combine constructs from multiple discrete theories, or incorporate concept of stigma, a powerful influence in setting the foundation of risk reduction behavior change.

Methods

A review of the literature identified health behavior models from which risk reduction interventions are developed. Insights from these studies informed the development of a new framework to inform ADRD risk reduction interventions. This new framework seeks to leverage constructs from the Social Ecological Model (SEM), Health Belief Model (HBM), Transtheoretical Model (TTM), and the Health Stigma and Discrimination Framework (HSDF) to better inform and understand the factors that influence ADRD risk reduction behaviors.

Result

This framework contains several concepts that predict why individuals will take action to reduce risk of ADRDs: individual factors, social‐environmental factors, self and public stigma, and perceptions. Our model also includes stages of change to integrate processes and principles of change, offering a temporal dimension for understanding behavior change. This novel framework can be utilized to inform both individual and community‐level interventions.

Conclusion

This new framework provides an innovative and alternative foundation for new ADRD risk reduction interventions. Applicable across a range of risk reduction behaviors, the model highlights the domains and pathways common across ADRD research and intervention implementation. This crosscutting approach will support a more efficient and effective response to addressing preventable risk factors for ADRDs, with the goal of application and realization. Further research is needed to assess the strengths and limitations of this framework in real‐world settings.
Changes in saccade parameters during non‐visual cognitive tasks in younger and older adults
Authors: Yang Hee Won , Kim Jeong Lan , Kim Ki Woong
Published: December 2023

Background

Although eye movements such as saccades are related to internal cognitive processes and are independent of visual processing, few studies have investigated whether non‐visual cognitive tasks simultaneously affect horizontal and vertical saccades in younger and older adults.

Method

We included 28 younger adults aged 20‐29 years and 26 older adults aged > 60 years through advertisements in community settings. All participants were free from major psychiatric, neurological, or ocular diseases. In the investigation, all participants performed the mental arithmetic task (MAT) and verbal fluency task (VFT). The primary measures were saccade parameters, including frequency, amplitude, and velocity.

Result

During the MAT and VFT phases, the frequencies of horizontal and vertical saccades increased (p = 0.0005 for horizontal saccade in MAT; p < 0.0001 for horizontal saccade in VFT; p = 0.012 for vertical saccade in MAT; p = 0.001 for vertical saccade in VFT), but were comparable between the MAT and VFT phases. The old group showed a slower vertical saccade than the young group during the task phase (p = 0.011 in the MAT phase; p = 0.006 in the VFT phase). The amplitude of the horizontal saccade decreased in both groups during the MAT phase compared with the resting phase (p = 0.013), but did not change significantly during the VFT phase.

Conclusion

Saccade parameters can change during non‐visual cognitive tasks. Saccades should be examined as a potential non‐invasive biomarker of cognitive disorders in future studies.
Plasma neurofilament light and brain volumetric outcomes among middle‐aged urban adults
Authors: Beydoun May A , Hooten Nicole Noren , Beydoun Hind A. , Weiss Jordan , Maldonado Ana I. , Katzel Leslie , Davatzikos Christos , Gullapalli Rao , Seliger Stephen , Erus Guray , Evans Michele K , Zonderman Alan B , Waldstein Shari R.
Published: December 2023

Background

Elevated plasma neurofilament light chain (NfL) is associated with dementia, but the specific underlying mechanisms are largely unknown. We examined cross‐sectional and longitudinal relationships of plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia, namely global and cortical brain, hippocampal and white matter lesion volumes (WMLV).

Method

Data were extracted from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004‐2009) and v2 (2009‐2013) plasma NfL exposure and ancillary sMRI data at vscan (2011‐2015, n = 179, mean v1 to vscan time: 5.4y). Multivariable‐adjusted linear regression models were conducted, overall, by sex, and by race, correcting for multiple testing with q‐values.

Result

NfL(v1) (Loge transformed) had a moderately strong association with larger WMLV at follow‐up vscan visit, after a period of 5‐6 years of follow‐up, overall (β = +2.131±0.660, b = +0.29, p = 0.001, q = 0.0029). Moreover, a 1 unit increase in NfLv2 was linked to a left hippocampal volume that was lower by 125 mm3 (p = 0.004, q = 0.015), using minimally adjusted models and mainly among males. Associations were largely unaltered by further adjustment for downstream health‐related factors.

Conclusion

In summary, plasma NfL may be an independent medium‐term (within 5 years) marker for increase in WMLV, and a short term (within 1 year) marker for smaller hippocampal volumes normalized to the intracranial volume, independently of other confounding factors. Therefore, plasma NfL holds promise as a blood‐based marker to predict future subclinical brain pathologies in middle‐aged adults.
An Examination of Reverse Causation in the Association between Serum Folate Deficiency and Dementia
Authors: Rotstein Anat , Kodesh Arad , Goldberg Yair , Reichenberg Abraham , Levine Stephen Z
Published: December 2023

Background

Evidence suggests that serum folate deficiency increases the likelihood of deficits in cognitive performance and neurological functioning. This situates serum folate as a possible biomarker positioned to modify the risk of dementia. However, the few observational studies that have examined the association between serum folate deficiency and the risk of dementia have shown inconsistent results. Prior studies of the associations between serum concentrations of folate and the risks of incident dementia have been unable to directly exclude the possibility that such associations are a by‐product of reverse causation. Reverse causation has been demonstrated to be particularly relevant to studies of dementia, because the neuropathological processes of dementia may start decades before a formal diagnosis is given. Thus, plausibly, serum folate deficiency is a consequence of preclinical dementia rather than its cause.

Method

A prospective cohort aged 60‐75 years (n = 27 188) without pre‐existing dementia for at least 10 years, was tested for serum concentrations of folate and followed up for dementia. Serum folate deficiency was classified as present (<4.4 ng/mL), otherwise absent. HRs and 95% CIs from competing risks Cox models were fitted to quantify the associations between serum folate deficiency and the risks of dementia. To examine reverse causation, the analysis was stratified by duration of follow‐up. Based on the median follow‐up cut point, the associations between serum folate deficiency and dementia were scrutinized in the first then second half of follow‐up. Serum folate deficiency was assumed to be little affected by preclinical dementia when the assessment was long before dementia onset and considerably affected when the assessment was nearer the diagnosis.

Result

The presence compared with the absence of serum folate deficiency was associated with higher risks of dementia (HR = 1.68; 95% CI 1.32 to 2.13; p<0.001). Evidence for reverse causation were moderate for dementia.

Conclusion

Serum concentrations of folate may function as a biomarker used to identify those at risk of dementia and mortality; however, reverse causation is likely. Further research is needed to examine the role of serum folate deficiency in dementia etiology.
Profiles of modifiable dementia risk factors in later midlife: a latent class analysis
Authors: Xiong Lisa Y. , Cogo‐Moreira Hugo , Wong Yuen Yan , Wu Che‐Yuan , Ruthirakuhan Myuri , Edwards Jodi D. , Rabin Jennifer S. , Lanctôt Krista L. , Black Sandra E. , Swardfager Walter
Published: December 2023

Background

In 2020, the Lancet Commission identified 12 modifiable risk factors that may increase dementia risk at the population level. At the individual level, these risk factors may co‐occur; therefore, this study aimed to identify profiles of dementia risk factors in later midlife, and to explore differences in biological markers associated with those profiles.

Methods

Participants aged 60‐64 without dementia at baseline and who identified as Caucasian were identified from the UK Biobank. Data for each risk factor (education, hearing loss, traumatic brain injury, hypertension, alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, air pollution, and diabetes) were collected using a standardized clinical assessment or through linkage of inpatient records. Latent class analysis was performed to identify latent classes of individuals; missing data were handled using full information maximum likelihood. A multigroup analysis was used to consider differences by self‐reported sex. Associations between the classes and a panel of 29 blood biomarkers across six broad categories (hormonal, inflammatory, kidney, liver, lipids, and metabolic) were explored using the Bolck, Croon, and Hagenaars (BCH) method, considering sex and controlling for age; pairwise comparisons between classes were made using z‐tests.

Results

Among n = 117,275 participants (males: n = 53,426, females: n = 63,849), a 4‐class solution was identified based on model fit statistics. Invariance testing revealed significantly different class solutions between sexes (Δχ2 = 11,615, Δdf = 52, p < 0.001). In general, the following four groups were identified in both males and females: low risk, psychosocial risk, cardiometabolic risk, and risk related to substance use (Figure 1). These classes differed in their blood biomarkers in both males and females, with the greatest differences observed in females. Specifically, the largest differences were observed between the cardiometabolic risk class vs. other classes, and in biomarkers for inflammation and metabolism (e.g. c‐reactive protein, triglyceride:HDL cholesterol ratio).

Conclusion

In both males and females in later midlife, four classes defined by modifiable dementia risk factors were identified. These profiles were associated with unique biomarker signatures. might further examine the effects of these risk factor profiles on dementia‐related pathophysiological changes.
A digital intervention to improve or maintain cognitive function in people at risk for cognitive decline
Authors: Marquard Inna A.
Published: December 2023

Background

The landmark FINGER study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) demonstrated that a multidomain intervention, including diet, exercise, cognitive training, and vascular risk monitoring, can improve or maintain cognitive functioning in at‐risk older people. However, implementing a multidomain intervention is challenging since it requires significant resources from healthcare professionals and often poses a considerable burden for senior people regarding costs, transportation, and time commitment. We developed a digital multidomain intervention for people at risk for cognitive impairment or with mild cognitive impairment (MCI) with the overall aim to prevent or alter cognitive decline and to offer an easily accessible solution.

Method

Based on the Finger study, we designed a multidomain intervention that was delivered daily (via a mobile app) over 90 days to 17 participants that were recruited online. Participants received assignments for activities related to body fitness, cognitive exercises, multisensory stimulation, and nutritional advice. They received educational material on metabolic risk factors for dementia. Participants were encouraged daily to participate in social activities. Outcomes were evaluated on days 0, 30, 60, and 90 using the Health‐Related Quality of Life Questionnaire (HRQOL) and the Subjective Cognitive Questionnaire.

Result

17 participants volunteered to participate. Participants between 41 and 80 years of age were included; 9 participants were 60 or younger and 8 participants were 61 or older. One‐third of the participants had a formal diagnosis of MCI. 15 participants completed the program (84% completion rate); After 90 days 71% of the participants indicated that their memory has improved, 50% reported improvements related to remembering recent conversations and, making plans and completing tasks. The number of reported healthy days increased from 13.6; 13.1 (mean, SD) to 21.4; 8.5 (mean, SD) and the days of limited activity dropped from 9.8; 10.1 (mean, SD) initially to 3.4; 3.5 (mean, SD) at the end.

Conclusion

The digital delivery of a multidomain intervention was feasible and accepted by participants, shown by a high completion rate. A digital dementia prevention and neurorehabilitation program may help overcome implementation issues of cost and time‐intensive in‐person programs and may improve clinical outcomes.
Midlife Hearing, Vision, Olfactory, and Motor Function Improve the Long‐Term Prediction of Cognitive Decline and Onset of Cognitive Impairment
Authors: Merten Natascha , Pinto A Alex , Paulsen Adam J , Chappell Richard J , Chen Yanjun , Engelman Corinne D , Ferrucci Luigi , Hancock Laura M , Johnson Sterling C , Schubert Carla R
Published: December 2023

Background

Dementia has a long preclinical phase with pathological changes starting decades before clinical symptoms. Early detection of high‐risk individuals in midlife has great potential for future targeted treatments and prevention but we currently lack non‐invasive, low‐cost screening tools. Sensory (hearing, vision, olfaction) and motor changes are common in aging adults and have been associated with cognitive impairment and dementia. We aimed to assess whether midlife sensory and motor function can improve risk prediction models of 10‐year cognitive decline and impairment in comparison to risk predictions using the CAIDE and Framingham Risk Score (FRS).

Method

This longitudinal study is based on N = 1529 (54% women, mean age 49 years, range = 22‐84) Beaver Dam Offspring Study participants with data from baseline, 5‐year, and 10‐year follow‐up that have undergone a neurocognitive review. We assessed hearing, vision, olfactory, motor, cardiovascular health, and health history, and calculated the CAIDE and FRS at baseline. We determined 10‐year cognitive decline (Trail‐Making Test B time;10% most decline) and cognitive impairment (neurocognitive case review by clinical expert panel). We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk prediction models of 10‐year incidence of cognitive decline or cognitive impairment. We used logistic regression models to calculate the area under the receiver operating characteristics curve (AUROC) for models using only CAIDE or FRS and for CAIDE‐sensory‐motor / FRS‐sensory‐motor models.

Results

Overall, 139 participants experienced cognitive decline and 240 developed a cognitive impairment. Adding sensory and motor measures improved AUROCs for cognitive decline models from 0.72[95% confidence interval 0.68–0.76] in CAIDE‐only to 0.77[0.73–0.81] in CAIDE‐sensory‐motor (p<.001) and from 0.71[0.67–0.76] in FRS‐only to 0.78[0.74–0.82] in FRS‐sensory‐motor (p<.001). Cognitive impairment AUROCs improved 0.59[0.55–0.63] to 0.65[0.61–0.68] (CAIDE;p<.001) and 0.59[0.55–0.63] to 0.65[0.61–0.69] (FRS;p<.01), after adding sensory and motor measures.

Conclusion

Including midlife hearing, vision, olfactory, and motor function improved risk prediction of long‐term cognitive decline and impairment in middle‐aged to older adults. Sensory and motor assessments could potentially become relevant cost‐effective and non‐invasive screening tools to identify those at high risk for neurodegeneration and cognitive decline early to target future prevention and intervention strategies.