bluuebunny/crossref_metadata_2025 huggingface dataset:
When in Camelot: Space invaders, neurodiversity and popular culture
Authors: Ventour-Griffiths Tré
Published: November 2024

This autobiographical reflection builds on Nirmal Puwar’s Space Invaders, where she frames women and people not racialised as white as `out of place’ and `out of space’ in white male spaces and places. For me disabled while Black, her work showed we may extend that conversation into how Critical Autism Studies, Disability Studies, and non/fiction publishing of autistic and otherwise disabled authors have been framed as white-only - those not white are seen as add-ons to the frame. Lack of `Black British’ disabled history, further lead me to write disability back into the history of the officially named yet stigmatising `Educationally Subnormal’ Scandal of the 1970s. It is also not difficult to see how `Educationally Subnormal’ [ESN] morphed into ableist term `Special Educational Needs’ [SEN]. The terminology is different but the underlying implications and inequalities remain the same. Going to school in Northants villages for near to the first fifteen years of my life, and playing cricket in those spaces for much longer, Puwar’s work may also point to the experiences of UK Black and Asian people who live and work in towns and the countryside - and in some cases may be able to trace their family history there going back many decades. My in-progress PhD research on Caribbean Northamptonshire Post-1945 takes that further in conversation with media, while I’ve also felt like a `space invader’ to much Black British media centralised on inner-cities - notably London. I found myself in Black characters appearing in rural period dramas, further to shows like Doctor Who and Merlin. From my rural schooling to disability and my questions of popular culture representations, these are all extended metaphors for the possibilities that we might all be space invaders in one context or another - even around people who look like us. This piece is a needed intervention showing there are a million and one ways to be human - just the mainstream is playing catchup, as per usual.
Extra virgin olive oil beneficial effects on memory, synaptic function, and neuroinflammation in a mouse model of Down syndrome
Authors: Li Jian-Guo , Leone Alessandro , Servili Maurizio , Praticò Domenico
Published: November 2024

Background:

Clinical and preclinical studies have shown that extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has beneficial effects on brain aging and cognition. Individuals with Down syndrome develop age-dependent cognitive decline and synaptic dysfunction. However, whether EVOO intake is beneficial in Down syndrome is not known.

Objective:

In this study, by implementing a mouse model of Down syndrome, we aimed to investigate the effect that chronic administration of EVOO has on memory, synaptic function, and neuroinflammation.

Methods:

Starting at 4 months of age Ts65dn mice were randomized to receive EVOO for 5 months in their diet, after which they were tested for learning and memory impairment. After euthanasia, synaptic function was measured in freshly obtained hippocampal slices, whereas brain tissues were assessed for inflammatory biomarkers.

Results:

Compared with controls, mice receiving EVOO had a significant improvement in learning and spatial memory. Additionally, field potential recordings showed that treated mice had an improvement in synaptic function. Finally, array analysis showed that EVOO modulated the expression levels of several inflammatory biomarkers.

Conclusions:

Chronic administration of EVOO to a mouse model of Down syndrome has beneficial effects on memory impairments, synaptic function deficits and neuroinflammation. Our findings provide additional support for the potential therapeutic effects of EVOO also in individuals with Down syndrome.
New tablet-based screening tool for assessment of cognitive decline in Nigeria
Authors: Anand Sulekha , Bayley Peter J , Clifford James O , Ashford J Wesson
Published: November 2024

We comment on the importance of the novel tablet-based screening tool for cognitive decline recently studied in Nigeria by Ogbuagu et al. TabCAT-BHA was administered on an iPad in urban and rural settings and was found to be a sensitive and culturally appropriate tool for assessing cognitive function and impairment. With accuracy, portability, speed, and ease of use, this study shows that such tests, computerized or online, have the potential to improve the screening of cognitive decline in diverse countries such as Nigeria, to facilitate early treatment and improved care and quality of life.
Involvement of inflammasomes in the pathogenesis of Alzheimer's disease
Authors: Beder Narimene , Belkhelfa Mourad , Leklou Hakim
Published: November 2024

Alzheimer's disease (AD) is a neurodegenerative disease with a long preclinical and prodromal stage near 20 years. The neuropathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and neuroinflammation, those lead to neuronal and synaptic loss. Important fact, oxidative stress participates in the AD development by promoting amyloid-β deposition, tau hyperphosphorylation. However, the inflammatory response and pyroptotic death are mediated by the aberrant expression of NLRP inflammasome activated caspase-1, which leads to cleavage pro-inflammatory cytokines such as pro-interleukin-1β and pro-IL-18. IL-1β, TNF-α, and IL-6 which amplify the neuroinflammation loop, are produce by activated microglia and astrocytes, that can serve as early diagnostic markers or therapeutic targets in AD. In this review, we summarize our current understanding of the role of inflammasome in the pathogenesis of AD, highlighting key issues that need to be addressed to improve the development of new therapies.
UBE3A: Bridging the gap between neurodevelopment, neural function, and neurodegenerative woes
Authors: Nash Kevin R , Jinwal Umesh K , Bhat Krishna Moorthi
Published: November 2024

Post-translational modifications (PTMs) of proteins play a significant role in normal protein function but can also be instrumental in disease pathogenesis. One critical yet under-studied PTM in disease is ubiquitination. Ubiquitin chain addition and substrate specificity are determined by a large spectrum of ubiquitin-ligating and -modifying enzymes, E3 ligases, whose expression levels and activities are tightly regulated in a cell-specific manner. While most ubiquitin chains can target proteins for proteasomal degradation, ubiquitination can contribute to other functions within the cell, including protein localization, protein activity, endocytosis, transcription, and autophagy. One E3 ligase, UBE3A, has garnered much attention because of its involvement in learning and memory, as well as its association with neurodevelopmental autism spectrum disorders (ASDs). However, more recent findings have suggested a potential involvement of UBE3A in neurodegenerative proteinopathies, where reduced UBE3A levels can lead to an enhanced rate of aggregate formation and cell death. Here, we review the literature on UBE3A in neurodevelopment, function, and neurodegenerative diseases and demonstrate that UBE3A could play a critical role in disease progression and cognitive function.
Added value of inflammatory plasma biomarkers to pathologic biomarkers in predicting preclinical Alzheimer's disease
Authors: Leclerc Haley , Lee Athene KW , Kunicki Zachary J , Alber Jessica
Published: November 2024

Background

Plasma biomarkers have recently emerged for the diagnosis, assessment, and disease monitoring of Alzheimer's disease (AD), but have yet to be fully validated in preclinical AD. In addition to AD pathologic plasma biomarkers (amyloid-β (Aβ) and phosphorylated tau (p-tau) species), a proteomic panel can discriminate between symptomatic AD and cognitively unimpaired older adults in a dementia clinic population.

Objective

Examine the added value of a plasma proteomic panel, validated in symptomatic AD, over standard AD pathologic plasma biomarkers and demographic and genetic (apolipoprotein ( APOE) ɛ4 status) risk factors in detecting preclinical AD.

Methods

125 cognitively unimpaired older adults (mean age = 66 years) who completed Aβ PET and plasma draw were analyzed using multiple regression with Aβ PET status (positive versus negative) as the outcome to determine the best fit for predicting preclinical AD. Model 1 included age, education, and gender. Model 2 and 3 added predictors APOE ɛ4 status (carrier versus non-carrier) and AD pathologic blood biomarkers (Aβ42/40 ratio, p-tau181), respectively. Random forest modeling established the 5 proteomic markers from the proteomic panel that best predicted Aβ PET status, and these markers were added in Model 4.

Results

The best model for predicting Aβ PET status included age, years of education, APOE ɛ4 status, Aβ42/40 ratio, and p-tau181. Adding the top 5 proteomic markers did not significantly improve the model.

Conclusions

Proteomic markers in plasma did not add predictive value to standard AD pathologic plasma biomarkers in predicting preclinical AD in this sample.
Intersectionality of gender with social determinants of health and asymptomatic Alzheimer's disease neuropathology
Authors: Besser Lilah M , Fuentes Anthony J , Zhang Jessica N , O’Shea Deirdre M , Galvin James E
Published: November 2024

Background:

Women comprise approximately two-thirds of Alzheimer's disease cases.

Objective:

This is the first known study to investigate the role of intersectionality between gender and other social determinants of health (SDOH) in the presentation of cognitive symptoms (i.e., being asymptomatic or symptomatic) among those with pathologically confirmed Alzheimer's disease.

Methods:

We studied 3107 individuals with Alzheimer's disease neuropathology (ADNP) confirmed at autopsy. Asymptomatic ADNP was defined as the absence of a clinical diagnosis of mild cognitive impairment (MCI) or dementia before death (versus symptomatic: diagnosis of MCI/dementia). SDOH included gender, education, ethnoracial group, living alone, and primary language. Multivariable logistic regression tested associations between SDOH and asymptomatic ADNP (versus symptomatic); models were also stratified by gender.

Results:

Women, Hispanics, those living alone, and more educated individuals were found to have higher odds of asymptomatic ADNP. Non-English speakers had lower odds of asymptomatic ADNP. Both women and men had higher odds of asymptomatic ADNP if Hispanic or living alone. In only women, non-English speakers had lower odds while in only men, more education was associated with higher odds of asymptomatic ADNP.

Conclusions:

Gender, education, ethnicity, primary language, and living alone, and intersectionality of gender with primary language, may differentially influence MCI and dementia diagnosis prior to death among those with underlying ADNP. These findings emphasize the need for future Alzheimer's disease research to prioritize social determinants of brain health including their intersectionality with gender and how to inform targeted interventions.
Education attainment and nutritional status in the prevention of cognitive impairment in the hospitalized Chinese elderly
Authors: Gao Zhao , Luo Tianjiong , Ye Chenyu , Cheng Kun , Qian Lichao , Cai Qingqing , Zhou Qiong , Fang Hui , Zhang Guancheng , Cai Shenyan , Shi Ming , Ji Ye , Zhao Letian , Zhu Yilin , Guo Weifeng
Published: November 2024

Background:

Effect of education attainment and nutritional status on the development of cognitive impairment in Chinese elderly has not been reported.

Objective:

To investigate the role of education and nutrition in preventing cognitive impairment in the hospitalized Chinese elderly.

Methods:

Cognitive function was examined using the scoring system of Mini-Mental State Examination (MMSE) domains performed under instruction of Physicians of Geriatrics. Generalized linear mixed-effect regression was used for analyzing the association of demographic factors (age and gender), socioeconomic factors (education attainment and monthly income), as well as health-related factors (nutritional status, comorbidity, anxiety, and depression) and MMSE scores.

Results:

Total 246 hospitalized Chinese elders were enrolled into this study. Of them, 96 participants were 60–70 years old, 65 participants were 71–80 years old, and 85 of them were 81 years or older. Of the examined factors, we found that age, education attainment, and nutritional status were significantly associated with the outcome of MMSE scores, while monthly income and health condition (comorbidity, anxiety, and depression) were not significantly associated with MMSE score. Furthermore, education attainment was significantly associated with majority of the MMSE domains, including orientation, registration, attention and calculation, recall, and most of language sub-domains.

Conclusion:

Education attainment and nutritional status were significantly associated with MMSE scores in the hospitalized Chinese elderly. Higher education and better nutritional status are protective factors for the development of cognitive impairment in the hospitalized elderly Chinese population.
Comparative accuracy of Mini-Linguistic State Examination, Addenbrooke's Cognitive Examination, and Depistage Cognitif de Quebec for the diagnosis of primary progressive aphasia
Authors: Fernández-Romero Lucía , Morello-García Florentina , Laforce Robert , Delgado-Alonso Cristina , Delgado-Álvarez Alfonso , Gil-Moreno María José , Lavoie Monica , Matias-Guiu Jorge , Cuetos Fernando , Matias-Guiu Jordi A
Published: November 2024

Background

Clinical diagnosis in primary progressive aphasia (PPA) is challenging. Recently, emphasis has been placed on the importance of screening evaluation. Three different screening tests that use different strategies based on the assessment of language (Mini-Linguistic State Examination, MLSE) or different cognitive domains (Addenbrooke's Cognitive Examination, ACE-III and Dépistage Cognitif de Québec, DCQ) have been proposed and independently validated. These tests aim to detect PPA and classify into the three main variants (non-fluent (nfvPPA), semantic (svPPA) and logopenic (lvPPA)).

Objective

This study aims to evaluate and compare the diagnostic capacity of these three instruments in PPA.

Methods

A cross-sectional study including 43 patients with PPA (nfvPPA ( n = 19), svPPA ( n = 8), and lvPPA ( n = 16)) and 21 cognitively unimpaired controls was conducted. Clinical diagnoses were established based on an extensive multidisciplinary assessment including neuropsychological assessment, fluorodeoxyglucose-positron emission tomography, MRI, and cerebrospinal fluid biomarkers. Both PPA patients and controls completed the three tests (MLSE, ACE-III, and DCQ).

Results

Internal consistency was excellent for the three tests. The area under the curve for the diagnosis of PPA was 0.950 for MLSE, 0.953 for ACE-III, and 0.933 for DCQ. Correlations between the three tests were high. The MLSE, ACE-III, and DCQ tests obtained adequate levels of discrimination between the variants of PPA, with accuracies between 76–79%.

Conclusions

This study confirms the validity of ACE-III, MLSE, and DCQ for the diagnosis of PPA and its variants. This suggests that detailed assessment of linguistic characteristics (MLSE) and non-linguistic features (DCQ, ACE-III) are relevant for the diagnosis and classification of PPA.
Remnant cholesterol and cognitive function: Evidence from the China health and retirement longitudinal study
Authors: Liu Hanrui , Luo Lili , Xia Juan , Wang Xiaonan , Luo Yanxia
Published: November 2024

Background:

Evidence on associations of remnant cholesterol (RC) and its variability with cognitive function is still lacking.

Objective:

To explore the association of RC and its variability with cognitive function.

Methods:

Participants were recruited from a population-based cohort, the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was assessed by a standardized questionnaire from CHARLS, with domains of episodic memory and mental intactness. A linear mixed effects model was used to analyze the association of RC with cognitive function, along with its variability (calculated as standard deviation [SD], coefficient of variation [CV], variability independent of the mean [VIM]), with results expressed as β (95%CI). Potential subgroup differences in the association of RC and its variability with cognitive function were also explored.

Results:

4234 participants were eventually included, with mean (SD) age of 57.4 (8.0) years. Each 10 mg/dL increase in RC was associated with 0.053 (95%CI: 0.096, 0.009) points, 0.021 (95%CI: 0.042, 0.000) points, 0.032 (95%CI: 0.064, 0.001) points decrease in global cognitive function, episodic memory, and mental intactness scores, respectively. Compared with the first tertile (T1) group of RC variability (calculated as SD, VIM), T3 showed a lower level in global cognition and episodic memory after multivariate adjustment. The potential modification effects of educational level on RC and its variability in relation to cognitive function were also identified.

Conclusions:

Among Chinese middle-aged and older adults, higher RC level were associated with worse cognitive function. Greater RC variability was also associated with worse cognitive performance, especially in memory function.
The association of the triglyceride-glucose index with Alzheimer's disease and its potential mechanisms
Authors: Zhang Zihao , Sheng Zehu , Liu Jiayao , Zhang Dandan , Wang Hao , Wang Lanyang , Zhu Yangke , Ma Lingzhi , Tan Lan
Published: November 2024

Background:

The correlation between Alzheimer's disease (AD) and the glucose-triglyceride (TyG) index remains undetermined.

Objective:

This study aimed to investigate the relationship between the TyG index and AD, as well as the relationship between the TyG index and cerebrospinal fluid (CSF) AD biomarkers and cognition.

Methods:

Six hundred twenty-eight non-dementia participants were included. The TyG index, pathological markers, and cognitive measures were studied using multiple linear regression. Also calculated using a multivariate Cox regression model were the hazard ratio (HR) and its 95% confidence interval (CI). Ten thousand bootstrap iterative causal mediation analyses were performed to investigate the potential mediating effect of AD pathology on cognition.

Results:

The TyG index was linked to CSF AD biomarkers (βAβ42 = 0.880; βTau = −0.674; βpTau = −0.884; βAβ42/pTau = 1.764; βAβ42/Tau = 1.554; βpTau/Tau = −0.210) and cognitive measurements (βMEM = 0.570; βEF = 0.535; βADAS11 = −0.789). Mediation analysis revealed that the TyG index may influence cognition via CSF AD biomarkers, including Aβ42, tau, and pTau. Furthermore, each 1-unit increase in TyG index was associated with a 29.5% reduction in the risk of incident AD.

Conclusions:

A delayed rate of cognitive decline and a reduced risk of AD were found to be correlated with higher levels of the TyG index, but this does not mean increasing TyG index levels is beneficial for health. Through AD pathology, the TyG index may influence AD and cognitive changes.
Social isolation and social cognition: A cross-sectional analysis
Authors: Grothe Jessica , Pabst Alexander , Röhr Susanne , Riedel-Heller Steffi G , Luppa Melanie
Published: November 2024

Background:

The impact of social isolation on social cognition is not entirely clear.

Objective:

The aim of the study is to investigate the association between social isolation and social cognition.

Methods:

In a population-based sample of 83 individuals aged 50+ years without dementia, we assessed the relationship between social isolation (measured by the Lubben Social Network Scale - LSNS-6) and performance on emotional recognition (measured by the Emotion Recognition Task (ERT)) and on Theory of Mind (ToM) abilities (measured by the Reading the Mind in the Eyes Test (RMET)), two core aspects of social cognition.

Results:

No significant association was found between social isolation and ToM abilities for both the unadjusted and adjusted models. Similarly, no significant association was observed between social isolation and emotion recognition.

Conclusions:

Further research is needed to understand the complex correlation between social relationships and cognitive health, particularly in different cognitive domains, adopting a life course perspective.
Perceptions of key informant neurologists before implementing anti-amyloid drugs in the Spanish departments of neurology
Authors: Matias-Guiu Jordi A , Álvarez-Sabín José , Botia Enrique , Casado-Naranjo Ignacio , Castellanos Mar , Frank Ana , Íñiguez Cristina , Jiménez-Hernández María Dolores , Jiménez-Jiménez Félix Javier , Láinez José-Miguel , Moral Ester , Pérez-Martínez David A , Rodríguez-Antigüedad Alfredo , Ruiz-Lavilla Nuria , Segura Tomás , Serrano-Castro Pedro J , Matias-Guiu Jorge
Published: November 2024

Background:

A deep knowledge of the healthcare system and the organization of neurology departments is important for planning and optimizing changes to facilitate the successful implementation of anti-amyloid antibodies treatments.

Objective:

We aimed to assess the necessary changes prior to introducing these therapies in our setting.

Methods:

We conducted a key informant survey among heads of departments of neurology from 16 hospitals in Spain. The questionnaire comprised questions about changes in the organization and functioning of the departments of neurology with the introduction of anti-amyloid drugs, changes in diagnosis and patient care, use of diagnostic techniques, patients, families and public information, resources allocation, and research.

Results:

Sixteen key informants completed the survey. They strongly agreed that the introduction of anti-amyloid drugs will impact the functioning of neurology services, especially in hospitals with dementia units. Consensus was reached regarding referring all Alzheimer's disease patients eligible for therapy to dementia units. There was also agreement on the need to expand the neurology services, day hospital units, extend visit durations, and hire more professionals, especially neurologists, neuropsychologists, and nuclear medicine physicians. Furthermore, consensus was achieved on increasing the use of MRI, amyloid PET, cerebrospinal fluid biomarkers, APOE genotyping, and the necessity of advancing blood biomarkers and tau tracers.

Conclusions:

Our study highlights the need for extensive changes within Spanish neurological departments to effectively integrate anti-amyloid antibodies. Implementing these changes is essential for the timely and equitable adoption of novel therapies.
The impact of sex on memory during aging and Alzheimer's disease progression: Epigenetic mechanisms
Authors: Scheinman Sarah B , Dong Hongxin
Published: November 2024

Alzheimer's disease (AD) is a leading cause of dementia, disability, and death in the elderly. While the etiology of AD is unknown, there are several established risk factors for the disease including, aging, female sex, and genetics. However, specific genetic mutations only account for a small percentage (1–5%) of AD cases and the much more common sporadic form of the disease has no causative genetic basis, although certain risk factor genes have been identified. While the genetic code remains static throughout the lifetime, the activation and expression levels of genes change dynamically over time via epigenetics. Recent evidence has emerged linking changes in epigenetics to the pathogenesis of AD, and epigenetic alterations also modulate cognitive changes during physiological aging. Aging is the greatest risk factor for the development of AD and two-thirds of all AD patients are women, who experience an increased rate of symptom progression compared to men of the same age. In humans and other mammalian species, males and females experience aging differently, raising the important question of whether sex differences in epigenetic regulation during aging could provide an explanation for sex differences in neurodegenerative diseases such as AD. This review explores distinct epigenetic changes that impact memory function during aging and AD, with a specific focus on sexually divergent epigenetic alterations (in particular, histone modifications) as a potential mechanistic explanation for sex differences in AD.
Circulating adipokines and MRI markers of brain aging in middle-aged adults from the community
Authors: Satizabal Claudia L , Himali Jayandra Jung , Conner Sarah C , Beiser Alexa S , Maillard Pauline , Vasan Ramachandran S , DeCarli Charles , Seshadri Sudha
Published: November 2024

Background

Midlife obesity is related to late-onset dementia. Studying adipose tissue-secreted adipokines in the context of brain aging may help us understand this association.

Objective

To investigate associations between adipokines and brain MRI markers in middle-aged adults from the Third-Generation cohort of the Framingham Heart Study.

Methods

Serum adiponectin, retinol-binding protein 4 (RBP4), fetuin-A, and Fatty Acid-Binding Protein 4 (FABP4) concentrations were measured by enzymatic immunoassays. MRI measures included total brain, cortical gray matter, hippocampal (total and anterior), lateral ventricular, and white matter hyperintensity volumes. We used linear regression models to separately relate adipokine concentrations to MRI measures, adjusting for potential confounders.

Results

We included 1882 participants (mean age of 48 ± 8 years, 54% women). Higher RBP4 concentrations were related to markers of brain atrophy, including smaller total (Beta ± standard error, −0.05 ± 0.02; p = 0.014) and cortical gray brain volumes (−0.06 ± 0.02; p = 0.004), and larger lateral ventricular volumes (0.06 ± 0.02; p = 0.006). Additionally, higher RBP4 (−0.06 ± 0.03; p = 0.042), Fetuin-A (−0.06 ± 0.03; p = 0.039), and FABP4 (−0.09 ± 0.03; p = 0.008) concentrations were associated with smaller anterior hippocampal volumes. Most associations remained after additional adjustment for vascular risk factors. In exploratory analyses, higher FABP4 was related to larger total brain in non-obese participants, and to smaller anterior hippocampal volumes in obese participants. Finally, higher adiponectin concentrations were related to smaller cortical gray, only in non-obese participants.

Conclusions

Our results suggest that adipokines are associated with markers of brain atrophy during midlife. Further studies are needed to replicate these findings and elucidate any potential mechanisms contributing to abnormal brain aging.
The partner paradox: How can we better understand shared cognitive decline in couples?
Authors: Vranceanu Ana-Maria , Szapary Claire
Published: November 2024

Shared cognitive decline among spouses remains in the early stages of being understood. In this commentary, we discuss Meng et al.'s systematic review and meta-analysis, which synthesizes the evidence for concordance of cognitive decline in couples. The study's methodology is robust and brings to light the challenges that persist within this field of research, namely the lack of specificity and standardization across outcomes and long-term follow-up. Here, we also situate the findings within the broader context of the many social influences on health and underscore the importance of dyadic preventive strategies and future longitudinal and mechanistic research.
Microbiota and cognitive impairment: Current challenges and future perspectives
Authors: Chapelet Guillaume , Noble Wendy , Derkinderen Pascal
Published: November 2024

Recent studies indicate that gut microbiota may play a crucial role in cognitive function. Individuals with cognitive impairment tend to have fewer beneficial gut bacteria and lower microbial diversity. Therefore, gut microbiota could be a potential biomarker for cognitive vulnerability. Further research is needed to understand the mechanisms and lifestyle factors affecting both microbiota composition and cognitive health. While the direct impact of microbiota and diet on cognitive impairment remains unconfirmed, this area holds promise for developing new preventive and treatment strategies.
Voluntary wheel running decreases amyloidogenic pathway and rescues cognition and mitochondrial energy metabolism in middle-aged female 3xTg-AD mouse model of Alzheimer's disease
Authors: dos Santos Jonathas Rodrigo , Catalão Carlos Henrique Rocha , Vulczak Anderson , Azzolini Ana Elisa Caleiro Seixas , Alberici Luciane Carla
Published: November 2024

Background

Evidence supports the neuroprotective effects of physical activity, either in experimental animal models or humans. However, the biological mechanisms by which physical exercise modulates dementia and Alzheimer's disease (AD) progression are still unclear.

Objective

This study investigated whether long-term (6 months) of voluntary wheel running induces neuroprotective effects in the pathogenesis of AD in middle-aged (8 months) female mice, focusing on energy metabolism.

Methods

A genetic mice model of AD (3xTg-AD) that performed wheel running presented changes in body metabolism and muscle oxidative profile, as well as restored discriminative and non-associative retention memories, evaluated by novel object recognition and open field tasks, respectively.

Results

In the hippocampus, these mice exhibited reduced levels of amyloidogenic AβPPβ fragment, phospho-Tau protein and phospho-Akt (activated form), without changes in phospho-AMPK (activated form). In addition, hippocampal mitochondria presented a restored respiratory function, characterized by lower coupling degree and weak contribution from complex I found in 3xTg-AD mice.

Conclusions

The results demonstrated that voluntary exercise improves cognitive parameters and biochemical hallmarks of AD, modulates Akt activation and enhances mitochondrial energy metabolism in hippocampus of middle-aged 3xTg-AD female mice, thereby reinforcing the neuroprotective role of physical exercise and the involvement of mitochondria in the etiology of the AD.
Progress of research and application of non-pharmacologic intervention in Alzheimer's disease
Authors: Tang Min , Guo Jie-jie , Guo Rong-xia , Xu Shu-jun , Lou Qiong , Hu Qiao-xia , Li Wan-yi , Yu Jing-bo , Yao Qi , Wang Qin-wen
Published: November 2024

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles formed by high phosphorylation of tau protein. At present, drug therapy is the main strategy of AD treatment, but its effects are limited to delaying or alleviating AD. Recently, non-pharmacologic intervention has attracted more attention, and more studies have confirmed that non-pharmacologic intervention in AD can improve the patient's cognitive function and quality of life. This paper summarizes the current non-pharmacologic intervention in AD, to provide useful supplementary means for AD intervention.
The safety and effectiveness of 40 Hz γ-tACS in Alzheimer's disease: A meta-analysis
Authors: Zhang Xinyang , Lv Renhua , Sun Yanqiu , Liu Timon Cheng-Yi
Published: November 2024

Background

The efficacy and safety of 40 Hz gamma transcranial alternating current stimulation (γ-tACS) in Alzheimer's disease (AD) are still uncertain.

Objective

This meta-analysis was conducted to investigate the therapeutic potential and safety of 40 Hz γ-tACS for AD.

Methods

The meta-analysis was conducted by systematically searching four databases from their start to 28 December 2023. Subgroup analyses were performed to identify the intervention effects of γ-tACS.

Results

Of the 7 included studies, γ-tACS has a notable impact on improving overall cognition [standardized mean difference (SMD): 0.49, 95% CI: 0.09 to 0.89], memory (SMD: 0.79, 95% CI: 0.18 to 1.41), and cholinergic transmission (weighted mean difference: −0.40, 95% CI: −0.43 to −0.37). Furthermore, subgroup analysis revealed that γ-tACS treatment had a substantial impact on enhancing memory targeting the left angular gyrus in both home (SMD: 3.12, 95% CI: 1.54 to 4.70) and non-home settings (SMD: 0.53, 95% CI: 0.24 to 0.82). However, γ-tACS had a positive effect on overall cognition in non-home settings (SMD: 0.55, 95% CI 0.11 to 0.98), but not in home settings (SMD: 0.22, 95% CI −0.76 to 1.20). Additionally, targeting temporo-frontal or bitemporal γ-tACS treatment resulted in improvement in overall cognition (SMD: 0.61, 95% CI: 0.06 to 1.16), but not targeting the left angular gyrus (SMD: 0.22, 95% CI: −0.76 to 1.20).

Conclusions

γ-tACS could be beneficial in enhancing cognition, memory and restoring cholinergic dysfunction in AD. The different selection of stimulation sites plays distinct roles. Meanwhile, AD patients are recommended to receive γ-tACS treatment at home.
The association between oral diseases and neurodegenerative disorders
Authors: Soiniemi Lauriina , Solje Eino , Suominen Anna Liisa , Kanninen Katja M , Kullaa Arja M
Published: November 2024

Background

The association between cognitive neurodegenerative disease and oral diseases has been under great interest recently. Several studies have suggested a connection between periodontitis and Alzheimer's disease (AD) or other neurodegenerative disorders.

Objective

This study aimed to review the potential mechanisms between oral diseases and neurodegenerative diseases.

Methods

The study was executed as a literature review of English-language publications from 2018–2022. The databases used for the search were PubMed, Cochrane, Scopus, and Web of Science. The search phrases used were “ neurodegenerative diseases” AND “ oral health” and “ neurodegenerative diseases” AND “ oral diseases.”

Results

The linkage between the two disease groups was observed in several distinct publications and several potential mechanisms were found. The link between periodontitis and AD proved to be the most significant. The effect was accentuated in elderly people where individuals possessed also other risk factors for neurodegenerative diseases and had generally worse oral health conditions.

Conclusions

Oral diseases may be risks for neurodegenerative changes along many different pathways. Good oral health should be acknowledged as a potential preventative or risk-reducing act against neurodegenerative diseases.
Associating faces with names and meals as a biomarker of early AD in cognitively healthy individuals
Authors: Andrés Pilar , Flores-Vázquez Juan Francisco , Enriquez-Geppert Stefanie
Published: November 2024

The Learning and Associative Memory (LAM) test is a face-name associative memory test created to detect early Alzheimer's disease (AD). In a recent study, it was administered to cognitively healthy individuals with different levels of amyloid-β (Aβ) and tau burden. The key findings for LAM were: 1) selective correlations with Aβ levels, 2) unique discriminatory power between A + and A- individuals, 3) significantly higher areas under the curve in receiver operating curve analysis. Future research should focus on comparing performance on the LAM and face-name associative memory tests to determine the most effective method for detecting early signs of AD.
Exploring phytochemical inhibitors of protein kinase C alpha for therapeutic targeting of Alzheimer's disease
Authors: Aazad AA , Choudhury Arunabh , Hussain Afzal , AlAjmi Mohamed F , Mohammad Taj , Prabha Sneh , Sharma Manoj Kumar , Shamsi Anas , Hassan Md Imtaiyaz
Published: November 2024

Background

Alzheimer's disease (AD) is characterized by neurodegeneration linked to amyloid-β (Aβ) plaques and tau protein tangles. Protein kinase C alpha (PKCα) plays a crucial role in modulating amyloid-β protein precursor (AβPP) processing, potentially mitigating AD progression. Consequently, PKCα stands out as a promising target for AD therapy.

Objective

Despite the identification of numerous inhibitors, the pursuit of more effective and precisely targeted PKCα inhibitors remains crucial.

Methods

In this study, we employed an integrated virtual screening approach of molecular docking and molecular dynamics (MD) simulations to identify phytochemical inhibitors of PKCα from the IMPPAT database.

Results

Molecular docking screening via InstaDock identified compounds with strong binding affinities to PKCα. Subsequent ADMET and PASS analyses filtered out compounds with favorable pharmacokinetic profiles. Interaction analysis using Discovery Studio Visualizer and PyMOL further elucidated binding conformations of selected compounds with PKCα. Top hits underwent 200 ns MD simulations using GROMACS to validate stability of the interactions. Finally, we propose two phytochemicals, Kammogenin and Imperialine, with appreciable drug-likeliness and binding potential with PKCα.

Conclusions

Taken together, the findings suggest Kammogenin and Imperialine as potential PKCα inhibitors, highlighting their therapeutic promise for AD after further validation.
Amyloid-β positivity is less prevalent in cognitively unimpaired KLOTHO KL-VS heterozygotes
Authors: Cook Noah , Driscoll Ira , Gaitán Julian M , Glittenberg Matthew , Betthauser Tobey J , Carlsson Cynthia M , Johnson Sterling C , Asthana Sanjay , Zetterberg Henrik , Blennow Kaj , Kollmorgen Gwendlyn , Quijano-Rubio Clara , Dubal Dena B , Okonkwo Ozioma C
Published: November 2024

Background

Klotho, encoded by the KLOTHO gene, is an anti-aging and neuroprotective protein. KLOTHO KL-VS heterozygosity (KL-VSHET) is hypothesized to be protective against the accumulation of Alzheimer's disease (AD) neuropathological hallmarks (amyloid-β (Aβ) and tau).

Objective

We examine whether being positive for Aβ (A+) or tau (T+), or A/T joint status [positive for Aβ (A + T-), tau (A-T+), both (A + T+) or neither (A-T-)] vary by KL-VS and whether serum klotho protein levels vary based on A+, T+, or A/T status in a cohort enriched for AD risk.

Methods

The sample consisted of 704 cognitively unimpaired, late middle-aged, and older adults; MeanAge(SD) = 64.9(8.3). Serum klotho was available for a sub-sample of 396 participants; MeanAge(SD) = 66.8(7.4). Covariate-adjusted logistic regression examined whether A + or T+, and multinomial regression examined whether A/T status, vary by KL-VS genotype. Covariate-adjusted linear regression examined whether serum klotho levels differ based on A+, T+, or A/T status.

Results

A+ prevalence was lower in KL-VSHET ( p = 0.05), with no differences in T + prevalence ( p = 0.52). KL-VSHET also had marginally lower odds of being A + T- ( p = 0.07). Serum klotho levels did not differ based on A+, T+, or A/T status (all ps ≥ 0.40).

Conclusions

KL-VSHET is associated with lower odds of being positive for Aβ, regardless of whether one is also positive for tau. Conversely, the likelihood of being tau positive did not differ based on KL-VS genotype. Our findings add to the growing KLOTHO literature and suggests the need for further research focused on understanding the mechanisms underlying KL-VS-related putative resilience to AD.
Detecting functional impairment with the Digital Clock and Recall
Authors: Ciesla Marissa , Toro-Serey Claudio , Jannati Ali , Banks Russell E , Gomes-Osman Joyce , Showalter John , Bates David , Tobyne Sean , Pascual-Leone Alvaro
Published: November 2024

Background

Distinguishing between mild cognitive impairment (MCI) and early dementia requires both neuropsychological and functional assessment that often relies on caregivers’ insights. Contacting a patient's caregiver can be time-consuming in a physician's already-filled workday.

Objective

To assess the utility of a brief, machine learning (ML)-enabled digital cognitive assessment, the Digital Clock and Recall (DCR), for detecting functional dependence.

Methods

We evaluated whether the DCR can help identify individuals at risk of functional deficits as measured by the informant-rated Functional Activities Questionnaire (FAQ) in older individuals including cognitively unimpaired, MCI, and dementia likely due to Alzheimer's disease.

Results

The DCR scaled well with FAQ scores, and ML classifiers trained on multimodal DCR features demonstrated strong performance in predicting functional impairment on a held-out test set. Differences in FAQ scores between DCR-predicted classes were comparable across key demographic groups.

Conclusions

The DCR can streamline the clinical decision-making, triage, and intervention planning associated with functional impairment in primary care.
Latin dance and cognitive impairment: Importance of una Mezcla of culture and science
Authors: Marquez David X. , Jaldin Michelle A. , Ocampo-Mota Jocelyn
Published: November 2024

Latinos are one of the fastest growing minority groups of the older adult population. More culturally relevant forms of physical activity, such as dance are needed to engage the older Latino population. Dance is considered a type of physical activity and is fun, challenging, and socially engaging. Our research, among others, has shown that dance is an effective form of physical activity and has been shown to improve memory and overall health. Our research demonstrates the significance of culturally relevant physical activity interventions; and the importance of involving the perceptions and input of community members from the intended population.
Keep neuroinflammation in mind when addressing Alzheimer's disease: A microglia perspective
Authors: Gessi Stefania , Mirandola Prisco , Merighi Stefania
Published: November 2024

This commentary offers a detailed examination of a newly published paper on the effects of small molecule decoys of amyloid-β (Aβ) aggregation on microglial activation. It was discovered that the NSC16224 decoy peptide inhibited proinflammatory cytokines TNFα and IL6 release from microglia in response to Aβ40 and Aβ42 treatment. The research addresses the potential of blocking a sequence of events that lead to the progression of Alzheimer's disease (AD). Here, we discuss the significance of these results in neuroinflammation, highlighting the greater implications for how decoy peptides would be interesting for the research and development of new drugs for AD therapy.
Estimating the rates of dementia using administrative data linked to cohort studies
Authors: Waller Michael , Flicker Leon , Fitzgerald Patrick , Almeida Osvaldo P , Anstey Kaarin J , Dobson Annette J
Published: November 2024

Background

Current estimates of dementia and Alzheimer's disease incidence and prevalence are required to understand the health needs of the elderly.

Objective

We used two Australia cohort studies, administrative datasets, and data linkage techniques to estimate dementia rates in Australia.

Methods

The study used Australian Longitudinal Study on Women's Health and the Health in Men Cohort Study. Records of dementia were obtained from linked sources and incidence and prevalence estimates were produced. Capture-recapture methods were used to estimate numbers of dementia cases not identified through data linkage.

Results

There were 3399 (28.5%) men with dementia identified from any source and 3767 (34.8%) women. Rates of dementia incidence and prevalence were similar between sexes but were raised in men once estimates of unidentified cases were included.

Conclusions

Cohort studies and linked administrative data can be used together to produce current estimates of dementia prevalence and incidence comparable to other population estimates.
High frequency post-pause word choices and task-dependent speech behavior characterize connected speech in individuals with mild cognitive impairment
Authors: Kleiman Michael J , Galvin James E
Published: November 2024

Background

Alzheimer's disease (AD) is characterized by progressive cognitive decline, including impairments in speech production and fluency. Mild cognitive impairment (MCI), a prodrome of AD, has also been linked with changes in speech behavior but to a more subtle degree.

Objective

This study aimed to investigate whether speech behavior immediately following both filled and unfilled pauses (post-pause speech behavior) differs between individuals with MCI and healthy controls (HCs), and how these differences are influenced by the cognitive demands of various speech tasks.

Methods

Transcribed speech samples were analyzed from both groups across different tasks, including immediate and delayed narrative recall, picture descriptions, and free responses. Key metrics including lexical and syntactic complexity, lexical frequency and diversity, and part of speech usage, both overall and post-pause, were examined.

Results

Significant differences in pause usage were observed between groups, with a higher incidence and longer latencies following these pauses in the MCI group. Lexical frequency following filled pauses was higher among MCI participants in the free response task but not in other tasks, potentially due to the relative cognitive load of the tasks. The immediate recall task was most useful at differentiating between groups. Predictive analyses utilizing random forest classifiers demonstrated high specificity in using speech behavior metrics to differentiate between MCI and HCs.

Conclusions

Speech behavior following pauses differs between MCI participants and healthy controls, with these differences being influenced by the cognitive demands of the speech tasks. These post-pause speech metrics can be easily integrated into existing speech analysis paradigms.
Neurologic dance training and home exercise improve motor-cognitive dual-task function similarly, but through potentially different mechanisms, among breast cancer survivors with chemotherapy-induced neuropathy: Initial results of a randomized, controlled clinical trial
Authors: Worthen-Chaudhari Lise C. , Crasta Jewel E. , Schnell Patrick M. , Lantis Kristin , Martis Joseph , Wilder Jacqueline , Bland Courtney R. , Hackney Madeleine E. , Lustberg Maryam B.
Published: November 2024

Background

Dual-task function is compromised among individuals with prodromal Alzheimer's disease (AD) and others at risk of developing AD. While exercise has been studied as a therapeutic candidate, the activity of social dance might promote dual-task rehabilitation as well or better than conventional exercise.

Objective

Compare effects of social dance versus home exercise on dual-task function and intervention adherence among individuals with increased risk of developing AD: survivors of breast cancer (BC) with chemotherapy-induced neuropathy (CIN).

Methods

Fifty-two (n = 52) survivors of BC with CIN-related symptoms and functional deficits were randomized (1:1) to 8 weeks of biweekly physical activity that took the form of partnered AdapTango dance (20 min) or home exercise (45 min) (NCT05114005, registered 08/15/2021). Primary outcome: dual-task function (TUG-Cog counting backward by 3 s). Secondary outcome: adherence. Exploratory outcomes: participant rating of perceived exertion in physical versus cognitive domains and cognitive load during dual-task performance.

Results

Both interventions improved Timed-Up-and-Go with cognitive task (TUGCog) after 4 weeks ( p < 0.001); gains were maintained at 8 weeks of intervention ( p < 0.001) and 1 month follow-up ( p < 0.001). The dance intervention met adherence feasibility criteria for 8 weeks; exercise met criteria for 4 weeks. The ratio of cognitive to physical exertion was higher for dance (1 to 1) than exercise (0.8 to 1.0; p < 0.001). Dance, only, was associated with reduced cognitive load ( p = 0.02).

Conclusions

Among survivors of BC with CIN, small doses of social dance improved dual-task function comparably to larger doses of home exercise, possibly due to differences in cognitive engagement.