bluuebunny/crossref_metadata_2025 huggingface dataset:
FERMT2 cleavage impacts APP metabolism in a Src‐dependent manner
Authors: NAJDEK Chloé , Demiautte Florie , Ayral Anne‐Marie , Flaig Amandine , Eysert Fanny , Lambert Jean‐Charles , Chapuis Julien
Published: December 2023

Background

FERMT2 has been identified as a genetic risk factor for AD. We have reported that the FERMT2 protein is a partner of APP and a loss of FERMT2 (kindlin‐2) function altered both axonal growth and long‐term potentiation in an APP‐dependent manner. In this study, we aimed to identify the molecular mechanisms leading to loss of FERMT2 function.

Method

We aimed to identify proteases and other factors that regulate the cleavage of FERMT2 protein, which appears to be a mechanism that modulates its functions. The impact on FERMT2 cleavage and molecular interactions were analyzed by Co‐IP and WB. Consequences of these molecular interactions between FERMT2 and its partners on APP metabolism were then investigated using HEK‐APP cell lines.

Result

We identified a caspase‐dependent cleavage of FERMT2 that could be a molecular mechanism involved in the regulation of cell adhesion processes by inhibiting the ability of FERMT2 to interact with its partners. Furthermore, these results suggest that c‐Src activity, already known to regulate FERMT2 pathway, may have an impact on APP metabolism through regulation of FERMT2 cleavage.

Conclusion

Altogether, our data provide new mechanisms for understanding the involvement of the genetic risk factor FERMT2 in the pathophysiological processes of AD.
The potential of immersive auditory‐cognitive training as a platform for studying hearing‐loss and cognitive decline
Authors: Frei Vanessa Laura , Giroud Nathalie
Published: December 2023

Background

Hearing loss (HL) is considered one of the top modifiable risk factors for cognitive decline and dementia. However, modifiability is still a challenge, with auditory‐cognitive training (ACT) representing a promising approach on top of hearing devices, although generalizability and transfer effects of such trainings remain a challenge.

Method

The objective of this study is to gain insights into the benefits of an ACT in audio‐visual immersion with the goal to improve speech comprehension in older adults at‐risk for dementia. Participants (with varying degrees of cognitive capacity and pure‐tone HL) answer questions about spoken content in a three‐dimensional immersive (virtual reality and stereoscopic stimulus presentation) conversation. Electroencephalography is used to measure neural responses simultaneously. Speech comprehension is measured on a behavioral level and concurrently cortical responses to speech as a function of baseline cognitive capacity, audiometric measures and varying cognitive demand is assessed. We address the challenge of generalizability and transferability by enriching our training with natural, relatable speech content, and increased immersion simulating day‐by‐day speech situations.

Result

We predict improved speech comprehension post immersive ACT and simultaneously gain a deeper understanding of the associated neural responses to speech with varying cognitive demands. We further intend to model these effects as a function of baseline cognitive capacity and degree of pure‐tone HL (data collection will start February 2022).

Conclusion

The central objective is whether immersive ACT has the potential to improve speech comprehension and to what extent such benefits depend on individual cognitive capacity and pure‐tone HL in older adults at‐risk for dementia. The design allows for both a within‐ and a between‐person perspective, whereby individual prerequisites, environmental and motivational factors will be considered. Finally, it allows for valuable considerations for future trainings, particularly regarding transferability and generalizability, while enabling increased engagement of individuals.
Prevalence of risk factors for dementia and association with cognitive alterations in an elderly population from the South of Brazil
Authors: Nakakogue Lindsey Mitie , Fonseca Rafaela Lopes
Published: December 2023

Background

The number of elderly people is increasing globally, including those who live with their dementia. It is currently the seventh leading cause of death worldwide and a leading cause of disability and dependence among older people. “The Lancet Commission’s 2020 update on prevention and monitoring care” evidenced 12 modifiable risk factors for dementia, suggesting that up to 40% of cases could be prevented or delayed if exposure to such factors were eliminated. In view of the increase in the elderly population and dementia cases, it is understood that preventive actions focusing on modifiable risk factors and early detection of dementia cases are necessary.

Method

Cross‐sectional, quantitative, descriptive study. Cognitive screening was carried out in patients over 60 years of age in an area of the territory of a Basic Health Unit using the Mini Mental State Examination (MMSE) and a survey of 12 (twelve) risk factors were investigated with questions related to: schooling, hypertension, hearing loss, smoking, obesity, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head trauma, exposure to tobacco and pollution. The interviews were performed from August to October 2022. About 146 individuals were selected and 73 interviews were carried out. Exclusion criteria were: bedridden elderly, those with compromised mobility or inability to understand. Statistical analysis was performed using the SPSS program using the Pearson’s chi‐square tests at a significance level of 5%.

Result

The present study identified a significant association between altered MMSE and low education, with a p‐value of 0.016. Of the illiterate patients, 47.6% had changes in the MMSE. Among individuals with 1 to 4 years of schooling, 82.8% had altered MMSE.

Conclusion

It can be concluded that low education is a risk factor for dementia, as evidenced in other studies. However, the need for further studies on cognitive assessment instruments should be considered, since low educational level can influence their results.
Hypoexcitation and connectome disintegration via whole‐brain semi‐empirical modeling in neurodegeneration
Authors: Coronel‐Oliveros Carlos , Gonzalez‐Gomez Raul , Sainz Agustín , Legaz Agustina , Fittipaldi Sol , Cruzat Josefina A , Herzog Ruben A , Moguilner Sebastian , Medel Vicente , Orio Patricio , Taglizucchi Enzo , Prado Pavel , Ibanez Agustin
Published: December 2023

Background

Neuroimaging biomarkers are intensively investigated in Alzheimer disease (AD) and the behavioral variant frontotemporal dementia (bvFTD). However, advanced ND biomarkers (i.e., PET and plasma) are expensive or not widely available/validated in underrepresented regions. EEG emerges as a promising alternative, due to its low‐cost, non‐invasiveness, portability, and wide availability in clinical research, although they lack mechanistic explications and robust modeling approaches. The aim of our work was to characterize the functional alterations in AD and bvFTD by combining EEG source‐level metaconnectivity (that captures high‐order interactions), anatomical priors, whole‐brain modeling, and a perturbational approach.

Method

Demographic‐matched data were collected via the Dementia Latin American Consortium (ReDLat; AD = 31, bvFTD = 18, Control = 46). From EEG source level recordings and using machine learning classifiers, we compared the pairwise functional connectivity with high‐order correlations captured by metaconnectivity. Then, neural mass modeling was used to propose biophysical mechanisms specifically ascribed to AD and bvFTD. Finally, a perturbational approach was employed to characterize the brain trajectories involved in the healthy and pathological states.

Results

Using metaconnectivity, we found specific subnetworks of brain regions compromised in AD and bvFTD, yielding an excellent accuracy in classifying each group of patients. Brain dynamics turned more “viscous” (uncoordinated) in patients and were associated with multimodal disease progression (years of disease, cognitive impairment, atrophy). Then a whole‐brain Jansen & Rit model simulated the functional disturbances in AD and bvFTD. The DTI connectome disintegration (reduced structural integration) and hypoexcitability (altered excitation/inhibition balance) triggered the metaconnectivity dynamics observed in AD and bvFTD. Finally, in‐silico stimulation identified key regions involved in the transition from disease (AD and bvFTD models) to a healthy brain dynamics.

Conclusion

Our work suggests new possible EEG markers for characterizing AD and bvFTD, linking the functional disturbances in patients to alterations in the connectome and E/I balance, and evidencing possible anatomical targets to restore the normal brain function.
Establishing the DementiaBank Delaware Corpus: An Online Multimedia Database for the Study of Language and Cognition in Dementia
Authors: Lanzi Alyssa M , Saylor Anna K , Fromm Davida , MacWhinney Brian , Cohen Matthew L
Published: December 2023

Background

To better understand the progressive decline of language abilities in aging and dementia, we expanded the quality and quantity of resources in DementiaBank — an open‐access database of multimedia spoken language interactions for the study of speech and language abilities across the progression of dementia. This work builds from the success of the TalkBank Project with regard to data sharing, transcription, analysis, and web delivery. Specifically, this work collected connected speech and language data to develop the new “Delaware corpus” and to share resources for future analyses.

Methods

Cognitively unimpaired adults (n = 20) and adults with mild cognitive impairment (MCI) (n = 35) completed the DementiaBank discourse protocol and a cognitive‐linguistic battery in a 90‐minute session by Zoom with an administrator. The discourse protocol elicited four types of discourse: picture description, story narrative, procedural discourse, and personal narrative.

Results

The new Delaware corpus is available on the DementiaBank website. Data include spoken language CHAT transcripts linked to audio, test results, and medical/demographic information for 55 participants. CHAT is a standardized format for transcription and coding that is compatible with the CLAN language analysis software. CLAN provides methods for linking transcripts to media and automatic computation of a wide range of morphosyntactic features and other complex linguistic analyses. Additional resources include an automatic speech recognition pipeline code with tutorials to help streamline the transcription process and a collaborative commentary system that allows consortium members to insert comments or codes directly into online transcripts linked to media files. The collaborative commentary system is beneficial for training research assistants in coding techniques and for collaborative analysis of discourse samples.

Conclusions

Detailed digital measurement of speech and language abilities of older adults with and without mild cognitive impairment may help advance research and clinical practice by expanding the subtyping of MCI to include speech/language profiles. Open‐access databases, like DementiaBank, facilitate research collaborations, support advancements in computational analyses, and improve research dissemination to advance dementia science. The next steps for this project involve recruiting more researchers, clinicians, and students to use the new protocol and contribute their data to grow the database.
NEUROPROTECTIVE ACTIVITY OF MICHELIA CHAMPACA AGAINST ALZHEIMER’S DISEASE IN RAT MODEL
Authors: Anawal Lingaraj , M Chandrashekhar V , Shalavadi Mallappa , M Chandrashekhar V
Published: December 2023

Background

Alzheimer’s disease (AD) is one of the neurodegenerative disease characterized by progressive loss of memory, thinking skills, language and other cognitive functions. The main objective of this work is to investigate neuroprotective activity of Michelia champaca against Alzheimer’s disease.

Method

Neuroprotective activity was carried out by colchicine induced Alzheimer’s disease on Sprague‐Dawley rats. Test group animals administrated with Ethanol extract Michelia champaca at dose of 200, 400, and 600mg/kg for 28 days. The Behavioural parameters were assessed using the Morris water maze test, Spontaneous locomotor activity using Open field Apparatus and Plus maze were performed at Days 0, 7, 14 and 28 on intracerebroventricular administration of colchicine for assessing the cognitive and gross behavioural activities in all groups. Biochemical parameter such as lipid peroxidation, glutathione, superoxide dismutase, catalase, total thiols and acetylcholinesterase were assessed and histopathology of brain tissue was assessed on the final day of the experiment.

Result

Ethanol extract of Michelia champaca shows a dose dependent neuroprotective activity by significant decrease in time latency of Morris water maze (p<0.001), Plus maze (p<0.001) increase in the Spontaneous locomotor activity (p<0.001) in EMC treated group compared to colchicine induced control group. Biochemical parameters showed significant decreases in lipid peroxidation (p<0.001) and increased in superoxide dismutase (p<0.001) catalase (p<0.001) glutathione (p<0.001) total thiols (p<0.001) and acetylcholinesterase level (p<0.001) in the EAM treated groups as compared with colchicine induced control group.

Conclusion

In conclusion, the present study suggests that administration of ethanol extract of Michelia champaca (EMC) possesses neuroprotective activity against colchicine induced cognitive impairment and associated oxidative stress.
Unique CSF lipid signature in asymptomatic subjects with a parental history of Alzheimer’s disease and its association with key apolipoprotein species
Authors: Labonté Anne , Picard Cynthia , Poirier Judes , Group Prevent‐AD Research
Published: December 2023

Background

CSF apolipoproteins exhibit lipid‐specific relationships (signatures) with Alzheimer’s disease (AD) pathological markers and APOE‐ε4 in asymptomatic individuals.

Method

Mass spectrometry‐based CSF lipid analysis was performed as described before (Sampaio et al. 2011). Lipids were extracted using a one‐step chloroform/methanol procedure. After extraction, resulting samples were analyzed by direct infusion on a QExactive mass spectrometer equipped with a TriVersa NanoMate ion source. Both MS and MSMS data were combined to monitor CE, DAG and TAG ions as ammonium adducts; PC, PC O‐, as acetate adducts; and CL, PA, PE, PE O‐, PG and PI as deprotonated anions. CSF levels of amyloid beta (Aβ42), and total Tau (t‐Tau) were measured by enzyme‐linked immunosorbent assay (Fujirebio, Sweden) whereas apolipoproteins (AI, AII, B, CI, CII, CIII, D, E and J) concentrations were assessed using the Luminex/Biorad assays kit (10‐plex magneto‐fluorescent immunoassays, BioRad, USA).

Results

To characterize human CSF lipid signatures and their relationship to several apolipoproteins in pre‐symptomatic AD, we profiled and analyzed 21 classes of lipid species (for a total of 796 sub‐species) and 10 apolipoproteins in 120 cognitively unaffected subjects exhibiting various levels of total tau, p(181)tau and Aβ42. Figure 1 illustrates the signature profile (after FDR correction) following stratification by APOE‐ε4 genotype at the time of recruitment, when no cognitive deficit was detected. Please note the preferential associations between phosphatidylethanolamine acetate species and apoB levels in the CSF in non‐ε4 carrier. The apoD‐lipid signature profile was found to be very different in ε4 versus non‐ε4 carriers. Figure 2 illustrates the different associations between lipid species and the different apolipoproteins found in the CSF as a function of AD severity (stratified using the CSF T‐Tau/Aβ42 ratio). As ratio increases (top tertile) and pathology unfolds, the lipid signatures become markedly altered, with strong effects observed with apoB, apoD and apoJ interactions.

Conclusion

Our results suggest that early amyloid and tau pathologies modulate the release of specific lipid species in the CSF which alters their relationship with apolipoproteins in an APOE‐ε4‐dependent manner.
Experiences of People Living with Dementia and their Care Partners in Participating in Outdoor Activities
Authors: Tavilsup Pattara , Abolarin Margaret , Jakubec Sonya , Roach Pamela , Smith Eric E. , Goodarzi Zahra , Kirkham Julia , Ismail Zahinoor , Svrcek Clark , Seitz Dallas
Published: December 2023

Background

There is increasing evidence for non‐pharmacological interventions to prevent dementia and delay disease progression. Outdoor recreational activities, such as visits to local parks, may help improve behavioural symptoms of dementia, cognition, and quality of life for both people living with dementia (PLWD) and their care partners. However, little is currently known about the experiences of PLWD and care partners about participating in outdoor activities. Understanding their experiences will help inform interventions and policies to promote participation in outdoor activities. Our objectives are to understand the experiences of PLWD and care partners in participating in outdoor activities.

Methods

We conducted semi‐structured interviews with PLWD and care partners, either alone or in dyads. Self‐reported characteristics of PLWD and care partners were recorded by online surveys. Interviews were recorded and transcribed for analysis. Interview questions included questions about the following topics: individuals relationships to outdoor activities; how these relationships may have changed over time; their current patterns of outdoor activities; perceived benefits of outdoor activities; potential risks of outdoor activities; and facilitators and barriers to participating in activities. The transcripts of interviews were coded by two independent members of the research team to identify common themes.

Result

A total of 10 participants (7 care partners; 3 PLWD) have participated in interviews to date. Themes identified from interviews include: 1.) Outdoor activities help people maintain a sense of identity and connection with their lives before being diagnosed with dementia; 2.) Both a diagnosis of dementia, stage of dementia, and physical changes associated with aging impact on the types of activities people participate in; 3.) Outdoor activities are associated with psychological benefits for PLWD and care partners; 4.) There are unique considerations for PLWD and care partners that need to be considered when designing outdoor spaces or programs for PLWD.

Conclusion

Outdoor activities are important to PLWD and care partners and help maintain connections to individuals' identities and are perceived as important to maintaining quality of life. The design of outdoor spaces and activities programs for PLWD and care partners need to incorporate their perspectives to maximize participation and benefits associated with outdoor activities.
Early loss of microglial p38α MAPK in the APPswe/PS1dE9 mouse model of Alzheimer’s disease alters soluble amyloid beta and reduces microglia co‐localization with amyloid plaques without affecting amyloid‐associated pathology
Authors: Frazier Hilaree N , Braun David J , Davis Verda A , Coleman Meggie J. , Rogers Colin B , Van Eldik Linda J. J.
Published: December 2023

Background

The p38 alpha mitogen‐activated protein kinase (p38α) pathway is linked to both innate and adaptive immune responses, and is currently under investigation as a target for drug development in the context of Alzheimer’s disease (AD) and other conditions with neuroinflammatory dysfunction (Asih et al., 2020). Preclinical data indicates that p38α inhibition can protect against AD‐associated neuropathology, although the cellular mechanisms and signaling pathways that underlie these effects have not been fully elucidated. Evidence suggests that inhibition of p38α may provide benefit by modulating microglial‐associated neuroinflammatory processes that contribute to the development of AD pathology. The present study tests this hypothesis by assessing early‐stage pathological changes in AD model mice following microglial‐specific knock out (KO) of p38α.

Methods

KO of p38α in microglia was accomplished in 5‐month‐old C57BL/6J wild‐type and amyloidogenic AD model (APPswe/PS1dE9) mice using a tamoxifen‐inducible Cre/loxP system under control of the Cx3Cr1 promoter. Animals underwent behavioral assessment on the open field test at 7.5 months of age and on the radial arm water maze test at 11 months of age, followed by collection of cortical and hippocampal tissues. Other endpoint measures included quantification of proinflammatory cytokines, assessment of amyloid burden and plaque deposition, and characterization of microglia‐plaque dynamics using a combination of ELISA, immunohistochemical, and immunofluorescent techniques.

Results

Suppression of microglial p38α did not alter behavioral outcomes, proinflammatory cytokine levels, or overall amyloid plaque burden, but did significantly increase hippocampal levels of soluble Aβ42 and reduced hippocampal colocalization of Iba1 and 6E10 in a subset of microglia in close proximity to plaques.

Conclusion

This work suggests that rather than reducing inflammation per se, microglial p38α inhibition in the context of early AD‐type amyloid pathology may alter hippocampal microglia‐plaque interactions. Additionally, these results support future investigations of microglial p38α signaling at different stages of disease, as well as the potential relationship between p38α and phagocytic processes in this particular cell‐type.

Funding: This work is supported by the National Institutes of Health (RF1 AG064859; F32 AG058456; T32 AG057461).
Impact of genetic risk in multidomain lifestyle preventive interventions
Authors: Solomon Alina
Published: December 2023

Background

Interactions between genetic and lifestyle‐related risk factors for dementia have been investigated mainly in observational studies, with conflicting results. Less is known about whether genetic risk factors for dementia (not just APOE4 allele but also polygenic risk beyond APOE4) have an impact on the effects of multidomain lifestyle preventive interventions on cognition. Although there is overlap between risk factors for dementia and e.g. cardiovascular diseases (CVD), it is unclear if CVD genetic risk may also have an impact on potential intervention benefits.

Method

The FINGER randomized controlled trial included 1260 participants aged 60‐77 years and at risk for dementia from the general Finnish population. Cognition improved more during 2 years in the multidomain lifestyle intervention (diet, exercise, cognitive training, social activities and cardiovascular risk monitoring) compared with control (regular health advice) group. Genetic risk scores for Alzheimer’s disease (AD‐GRS, excluding APOE) and CVD‐GRS were selected based on existing literature, and calculated using GWAS data from FINGER participants.

Result

Previous findings indicated that the FINGER intervention had clear cognitive benefits among APOE4 carriers. Preliminary results suggested a less straightforward impact of AD‐GRS, especially after adjustment for APOE4. There seemed to be a pattern of more intervention‐related cognitive benefit among participants with lower compared with higher CVD‐GRS.

Conclusion

APOE4, AD‐GRS and CVD‐GRS may have different impact on the cognitive benefits of multidomain lifestyle interventions for dementia prevention. Ongoing World‐Wide FINGERS trials in populations with a variety of genetic profiles will create opportunities for more detailed investigation of genetic‐lifestyle interactions in the context of preventive interventions.
Multi‐Trajectories of Blood Pressure and Cognitive Function in U.S. Adult Population
Authors: Xu Hanzhang , Ford Cassie , Clark Amy G , Yang Qing , Green Michael D. , Lynch Scott M. , Navar Ann Marie , Xian Ying , Peterson Eric D. , Dupre Matthew E.
Published: December 2023

Background

Elevated blood pressure (BP) levels are associated with cognitive impairment and the development of Alzheimer’s disease and related dementias (ADRD). However, long‐term co‐occurring changes in BP and cognitive function are poorly characterized.

Method

Using data from the 2006‐2018 Health and Retirement Study (HRS), we identified 21,968 adults aged 50 years or older without ADRD at baseline (median follow‐up 8 years). Cognitive function was measured at each wave occurred every 2 years using a summary score that included immediate/delayed word recall, serial 7’s test, objective naming test, backwards counting, recall of the current date, and naming the president/vice‐president (score range = 0‐35). BP was measured at each wave in random half samples. We used group‐based trajectory models to identify age‐based multi‐trajectories of cognitive function and both systolic and diastolic BP from age 50 to 90.

Result

Four distinct co‐occurring trajectories of systolic BP and cognitive decline were identified (Figure 1): moderately‐increasing systolic BP with moderate and accelerated cognitive decline(Group 1; 34.6%; 95% CI, 33.2%‐36.0%; n = 7,600), moderately‐increasing systolic BP with high levels of cognitive function and minimal decline (Group 2; 39.6%; 38.2%‐41.0%; n = 8,699), elevated‐increasing systolic BP with low and accelerated cognitive decline (Group 3; 14.0%; 13.3%‐14.8%; n = 3,075), and high‐stable systolic BP with moderate cognitive decline (Group 4; 11.8%; 10.5%‐13.0%; n = 2,594). Findings were similar for co‐occurring trajectories of diastolic BP and cognitive decline, but changes in diastolic BP were attenuated with age. Male, White, and more highly educated were most likely to be in Group 2 than other groups. Black adults were more likely to experience elevated BP and/or accelerated cognitive decline: Black men were most likely to be in Group 3. Among women, Black race was associated with increasing likelihood of belonging to Group1 & 4.

Conclusion

Trajectories of systolic BP and cognitive decline varied throughout middle‐to‐late adulthood. The distinct patterns emerging that may also align with demographic differences in the prevalence of ADRD and cardiovascular risk factors. Additional research is needed to further address the underlying mechanisms contributing to age‐related changes in BP and cognitive decline.
Sex modifies the associations of regional fat with cognitive functioning and AD‐related brain volumes, in Israeli middle‐aged adults at high AD risk
Authors: Golan Sapir , Boccara Ethel , Ravona‐Springer Ramit , Inbar Yael , Zelicha Hila , Shai Iris , Livny Abigail , Bendlin Barbara B , Lesman‐Segev Orit H. , Yore Iscka , Azuri Joseph , Beeri Michal S
Published: December 2023

Background

High body mass index (BMI) has been consistently linked to poorer cognition and higher dementia risk, with different associations in males and females. However, BMI does not represent well specific fat depots. We examined in middle‐aged adults at high Alzheimer’s dementia (AD) risk, whether regional abdominal adiposity is associated with cognitive functioning and brain indices and whether sex modifies these associations.

Methods

204 healthy Israeli middle‐aged AD offspring (59.44 [SD = 7.60] years old, 60% females) underwent abdominal Magnetic Resonance Imaging (MRI) to quantify hepatic, pancreatic, and peripheral fat %‐visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A broad cognitive battery defined global cognition and specific cognitive domains (episodic memory, working memory, executive functions, and language). A subsample of 142 participants had brain MRI to assess regional brain volumes (total gray matter [GM], hippocampus, and inferior, middle, and superior frontal gyrus [IFG, MFG, and SFG, respectively]). Partial correlations examined associations of regional abdominal adiposity with cognitive functioning, and brain indices, adjusting for age, sex, education, BMI, and time interval between abdominal MRI and the dependent variable. Fisher‐z transformation compared partial correlations between males and females.

Results

In the whole sample, the only significant association was of higher hepatic fat % with lower GM volume (r = ‐264, p = 0.003), with similar associations in males and females. Only in males, higher pancreatic fat % was associated with lower global cognitive functioning (Males: r = ‐.276, p = .028; Females: r = 0.009, p = 0.93), executive functioning (Males: r = ‐0.267, p = 0.034; Females: r = 0.015, p = 0.87) and episodic memory (Males: r = ‐0.278, p = 0.027; Females: r = 0.068, p = 0.484) as well as with lower IFG volume (Males: r = ‐0.343, p = .017; Females: r = 0.117; p = 0.326). Also only in males, higher VAT% was associated with SFG volume (Males: r = .261, p = .045; Females: r = ‐0.198; p = 0.091).

Conclusion

In middle‐aged males, but not in females, at high AD risk, regional abdominal adiposity, primarily pancreatic fat, was associated with lower cognitive functioning and lower AD‐related brain volumes. Results suggest sex differences in the contributions of fat to brain and cognitive aging. Since fat % is modifiable, these results may suggest that interventions to decrease distinct fats for the advancement of brain health must be sex‐specific.
Poor Diet and Lower Neuropsychological Performance in a rural setting: The Bogalusa Heart Study
Authors: De Anda‐Duran Ileana , Potts Kaitlin S , Libon David J , Carmichael Owen T. , Bazzano Lydia
Published: December 2023

Background

Poor diet has been associated with insidious onset dementia. The Alternate Healthy Eating Index (AHEI) can capture overall nutrient quality and individual/population eating behaviors. Higher adherence to AHEI has been associated with a lower risk of incident dementia and better cognitive function in late life. However, most evidence comes from high‐income populations from urban areas. Here, we examined the adherence to AHEI and its association with cognitive function in midlife among Black and White individuals from a community cohort in the rural, low SES area of Bogalusa, Louisiana.

Method

This cross‐sectional analysis considered 1,040 participants from the Bogalusa Heart Study (mean age 48.1 ± 61% female, 31% Black) with a complete neuropsychological (NP) assessment and food frequency questionnaires. (AHEI‐2010 score, range 0‐110). Regression models using GEE accounted for clustering effects of neighborhood factors/SES using census‐track level codes and estimated the association between quintiles (Q1‐Q5) of AHEI‐2010 and a global cognitive z‐score (GCS) and cognitive domains.

Result

Individuals in Q5 (healthiest) tended to be female (68%, p = 0.03), significantly older (49.3 ± 5, p<0.001), with higher education (³ college 56%, p<0.001), and AHEI‐2010 scores from 53.38‐79.2. Compared with participants in Q1. Those in Q5 had higher GCS [ß (95% CI):1.71 (0.85, 2.57); p<0.001] after adjusting for age, sex, race, and the ACS‐Index of concentration at the extremes (to account for neighborhood‐level SES). Similarly, those with the healthiest diet had higher NP z‐scores within the domains of executive function, attention and speed processing information, and episodic memory. However, these associations were not significant after adjusting for education. (Table 1) For episodic memory, individuals in quintile 4 had higher NP z‐scores after adjusting for education [0.36 (0.07, 0.65); p = 0.01], and the trend across quintiles was also significant in all models and after adjusting for education [p = 0.03].

Conclusion

As early as midlife, Black and White individuals from rural settings with greater adherence to healthy dietary patterns have better NP performance across different neurocognitive domains. These results strengthen previous evidence suggesting that diet quality may be a potential avenue of intervention to prevent cognitive decline and aid health disparities.
Loneliness and Global Cognitive Functioning: A Study of Racially and Ethnically Diverse Older U.S. Adults
Authors: Camacho David , Aranda Maria P. , Reid M. Cary , Wethington Elaine R
Published: December 2023

Background

Few studies have examined the association of loneliness and cognitive functioning in the U.S., and these rarely assessed whether this relationship varied by race. We assessed this association in a large sample of U.S. Black, Latino, and White adults (ages≥50).

Method

We analyzed Wave 3 of the National Social Life, Health, and Aging Project (N = 2,334). We examined loneliness via one item from the CES‐D (“Direct”) and the Felt Loneliness Measure (NFLM; “Indirect”), and cognitive functioning via the Chicago Cognitive Functioning Measure (CCFM; higher scores indicated better functioning). We used weighted generalized linear models to examine the main and interactive effects of loneliness (direct and indirect in separate models) and race on CCFM scores. We adjusted for: sociodemographic and other salient factors (e.g., chronic disease, depressive symptoms, living alone).

Result

Mean age was 67 years, 53.5% were female, 11.5% were Black and 8.1% Latino. 42% of sample was lonely on at least one measure; 29% (direct) and 30% (indirect). The relationship between loneliness measures was significant, X2 (1, N = 2,344) = 594.64, p = .001. However, only 40% of lonely individuals were identified as lonely on both direct and indirect assessments. Direct: loneliness was inversely (β̂ = ‐.291, p = .013) associated with CCFM scores and this association did not vary by race. Indirect: loneliness was positively associated (β̂ = 1.504, p = .001) with better CCFM scores for Latinos only.

Conclusion

Loneliness appears to be an important predictor of cognitive functioning. However, the association of loneliness and cognitive functioning may vary as a function of measurement and race. Further research is needed, particularly to understand the counterintuitive finding for Latinos. For example, future research should explore how different measures of loneliness (direct vs. indirect), and dimensions of loneliness (social, emotional, existential, chronicity), relate to global and individual cognitive domains. Also, research is needed to explore how diversity within groups (nativity, acculturation, migratory status), contextual (established vs. new destination states), and cultural factors (stigma, beliefs, coping) influence cross‐sectional and longitudinal relationships between loneliness and cognitive functioning. Finally, findings also support the need for research on interventions to prevent cognitive decline targeting loneliness.
Financial toxicity in dementia caregiving
Authors: Hart Danielle M , Leggins Brandon , Sanches Clara , Chiong Winston
Published: December 2023

Background

Dementia caregiving is associated with significant financial costs. The term “financial toxicity” has been used in many care settings to describe the negative effects of medical expenses on both financial security and health‐related quality of life. Here, we utilize the validated COmprehensive Score for financial Toxicity (COST) to examine the experience of financial toxicity in American dementia caregiving.

Method

We conducted a nationally representative survey of 317 US dementia caregivers, oversampling non‐Hispanic Black (n = 75) and Hispanic (n = 61) caregivers, with the COST questionnaire. Financial toxicity was defined as COST <26 and further categorized as mild (COST ≥14 & <26), moderate (COST >0 & <14), or severe (COST = 0) according to the measure’s predetermined cut points. COST was treated categorically to generate descriptive statistics and continuously for linear regression. We built nested multivariable models to use in our regression‐based analysis. The base model included key caregiver demographics (age, gender, race/ethnicity, rurality), to which the fully adjusted model added supplementary caregiver demographics, care recipient clinical characteristics, and caregiver‐recipient relational characteristics.

Result

Survey‐weighted categorical analysis revealed 52.7% of American caregivers experience some degree of financial toxicity. Of those who experience financial toxicity, 73.1% are classified as mild, 25.7% as moderate, and 1.2% as severe. Financial toxicity was identified in 69.5% of non‐Hispanic Black, 54.1% of Hispanic, and 42.3% of non‐Hispanic White caregivers, with non‐Hispanic Black caregivers significantly more likely to experience financial toxicity compared to non‐Hispanic White caregivers (p = 0.017). In our base linear regression model, older caregiver age was protective against financial toxicity (p = 0.024). Caregiver employment status mediated this effect in the fully adjusted model, with retirement protective against financial toxicity (p <0.001). In contrast, unemployment predisposed caregivers to financial toxicity (p <0.001).

Conclusion

Most dementia caregivers in the US experience financial toxicity, with Non‐Hispanic Black caregivers bearing the highest risk. Older caregiver age protects against financial toxicity, likely due to the relationship between age and retirement.
The association between cognitive reserve and cognitive trajectories among older adults in Europe
Authors: Khalaila Rabia , Dintica Christina S. , Yaffe Kristine
Published: December 2023

Background

The literature on cognitive reserve (CR) and cognitive trajectories is limited in in the using of individual CR measures rather than composite CR measure. Moreover, to date, the findings about the association between CR and cognitive trajectories are conflicting and inconsistent.

Aims

To examine the longitudinal association of a composite CR measure and each individual indicator of CR on cognitive decline, both combined and on individual domains, over 6‐years follow up, adjusting for age, gender, number of chronic diseases, functional disability and physical activity

Methods

We conducted a longitudinal analysis using a cohort study on 55,340 participants from 16 European countries, aged 50 and more taken from the survey of health, Aging, and Retirement in Europe (SHARE). We used cognitive performance assessments (including immediate memory, delayed memory, verbal fluency and numeracy) and information on CR factors (encompassing education, occupation and cognitive activities) collected in four waves conducted at 2‐years interval from 2011 to 2017. First, structural equation modeling was used to construct the composite CR score, and then was analyzed by tertile. Finally, linear mixed‐effect models were used to examine the study aims.

Results

At baseline, compared with highest CR, middle and lowest CR showed large differences in combined cognition and in all individual domains. At the longitudinal results revealed that compared with the highest CR, the lowest CR was related to a faster decline in composite cognition score over time, despite the small difference, it remains significant (β: ‐0.02, 95% confidence interval [CI]: ‐0.03 to ‐0.01), as well as in all specific cognitive domains. However, no association was found for the middle CR trajectory. Among the individual CR measures, education was associated with better cognitive performance over time (β: 0.01, 95%CI: 0.01 to 0.01) and occupation complexity was associated with less decline over time (β: ‐0.01, 95%CI: ‐0.01 to ‐0.00), but cognitive activities were not associated with cognition.

Conclusions

The composite CR provides a comprehensive measure in preserve cognitive functions and in avoiding cognition decline, more than using individual CR indicator.
Exosomal IL‐12p70 is increased in Minority Participants at Risk for Alzheimer’s Disease
Authors: Winston Charisse N. , Rissman Robert A
Published: December 2023

Background

Detecting toxic proteins, including Aβ and p‐tau species within neuronal (NEVs) and astrocyte extracellular vesicles (AEVs) has initiated an ongoing effort to assess the clinical utility of EVs as potential biomarkers for Alzheimer’s Disease (AD) and other AD‐related dementias (ADRDs). African Americans (AAs) and Hispanics are approximately 1.5 to 2 times more likely to develop AD and ADRD as compared to non‐Hispanic Whites (NHW). Specifically, AAs are more likely to have higher levels of chronic stress, inflammation, and vascular related co‐morbidities. Here, we assess the proinflammatory phenotype of EV cargo loads of different cellular origins for novel biomarker assessment amongst Hispanic and AA subjects with AD.

Method

Plasma EVs derived from normal controls and AD subjects (NHW, Hispanics, AAs, n = 20/group) were extracted, precipitated using a polymer‐based isolation method (ExoQuick), and enriched against neuronal (L1CAM), astrocyte (GLAST), and microglial (TMEM119) sources using magnetic immunocapture and fluorescence‐activated cell sorting (FACS). ONI Nanoimager was used to characterize EVs by size and EV marker profiling was done via ELISA. Concentrations of proinflammatory cargo proteins were quantified using MSD immunoassay (V‐PLEX Proinflammatory Panel 1). Patients were stratified based on race, cognitive status, sex, and APOE genotype.

Result

Neuronal and glial EVs were similar in size and distribution. Plasma concentrations of EV marker CD81 were not statistically different between the three EV preparations. Plasma concentrations of IL‐12p70 were significantly increased in NEVs derived from demented NHW and Hispanics as compared to AAs. Increased plasma NEV and AEV concentrations of IL‐12p70 were positively correlated with APOE4 carrier status. No difference was observed based on sex. No significant difference was observed in MEV concentrations of IL‐12p70 based on race, cognitive status, sex, and APOE genotype

Conclusion

Differential pro‐inflammatory phenotypes of EV cargo exist amongst Hispanics and AAs as compared to NHW. Plasma NEV concentrations of IL‐12p70 may serve as a novel biomarker for identifying AD amongst AAs subjects. The biomarker capabilities of additional proinflammatory‐related EV cargo proteins will be investigated in a larger sample cohort of normal controls and AD subjects.
Strategies for managing patients with moderate to severe Alzheimer’s disease: high‐dose donepezil vs. memantine combination
Authors: Shim YongSoo , Jung San
Published: December 2023

Backgrounds

When dementia patients who took already a maintenance dose of 10mg donepezil get worse to advanced stage, clinicians would consider and select which one is better between higher‐dose donepezil (23 mg/day) and memantine combination.

Objectives

To compare the clinical benefits between high‐dose donepezil and memantine (20 mg/day) combination in moderate to severe Alzheimer’s disease

Methods

A single center, retrospective, observational study was conducted. Patients with moderate to severe AD who were treated with a stable dose of donepezil were included. They started further treatments such as higher‐dose donepezil or memantine combination because they showed poor or waning response to a maintenance dose. After 6 months follow‐up, clinical efficacy and safety were compared between two groups, higher‐dose donepezil and memantine combination.

Results

A total of 108 patients, 35 with higher‐dose donepezil and 75 with memantine combination, were included. Baseline characteristics such as age, sex, education, MMSE, and CDR were similar between groups. After follow‐up, changes of MMSE and CDR were not different. Treatment responses measured as CGI‐C were as follows: 41.3% (improved 31, not changed 25, and worse 9) of patients improved after memantine combination and 22.9% (improved 8, not changed 12, and worse 15) improved after higher‐dose donepezil (p = 0.069). Adverse events were not different. Among patients with memantine combination, those who had no benefits to the initial donepezil showed better responses (27 vs. 48). Patients who had benefits to lower dose of donepezil showed better responses (24 vs. 11) after higher‐dose.

Conclusion

Both of higher‐dose donepezil and memantine combination, which are approved as effective in moderate to severe AD, were not different in clinical benefits and safety. Although not statistically significant, treatment responses showed some differences. Patients who had shown good response at the time of the initial therapy of donepezil preferred higher‐dose donepezil over memantine combination, whereas those who did not respond to the initial donepezil had more effective after memantine was added. Further studies including randomized blind trials could strengthen these findings.
The influence of baseline sleep on exercise‐induced cognitive change in older adults: A randomised clinical trial
Authors: Sewell Kelsey R , Rainey‐Smith Stephanie R , Peiffer Jeremiah J , Sohrabi Hamid R , Frost Natalie , Markovic Shaun J , Erickson Kirk I. , Brown Belinda M
Published: December 2023

Background

Observational studies consistently demonstrate that physical activity is associated with enhanced cognitive function and reduced risk for dementia. However, there remains significant heterogeneity in study findings regarding the effect of exercise interventions on cognitive function. Individual variation in sleep behaviours are hypothesized to be a source of this variability in the effectiveness of exercise to influence cognition, however this has not yet been investigated. Thus, the current study aimed to 1) investigate the influence of a 6‐month exercise intervention on sleep pre‐ and post‐intervention and 2) investigate whether baseline sleep measures moderate exercise‐induced cognitive changes.

Method

We utilised data from the Intense Physical Activity and Cognition (IPAC) study (n = 89), a 6‐month moderate intensity and high intensity exercise intervention, in cognitively normal community‐dwelling older adults aged 60‐80 years (68.76 ± 5.32). Exercise was supervised and completed on a stationary exercise bicycle, and cognitive function was measured using a comprehensive neuropsychological battery administered pre‐ and post‐intervention. Sleep was measured using the Pittsburgh sleep quality index (PSQI) to yield measures of sleep duration, efficiency, and sleep latency.

Result

There was no effect of the exercise intervention on any sleep outcomes from pre‐ to post‐intervention. There was a significant moderating effect of baseline sleep efficiency on both episodic memory and global cognition within the moderate intensity exercise group (β = ‐0.024, SE = 0.008, p = .004; β = ‐0.011, SE = 0.005, p = .036), such that those with poorer sleep efficiency at baseline showed greater exercise‐induced cognitive improvements.

Conclusion

These results indicate that those with poorer sleep may have the greatest exercise‐induced cognitive benefits and that baseline sleep behaviours may be an important source of heterogeneity in previous exercise interventions targeting cognitive outcomes.