Positive 14-3-3 protein in cerebrospinal fluid followed by poppy-induced delayed post-hypoxic leukoencephalopathy: A case report.

Background: Delayed post-hypoxic leukoencephalopathy (DPHL) is characterized by a biphasic clinical course, with complete recovery from coma to a fully conscious state lasting one to four weeks (lucid interval), followed by abrupt neurological deterioration as an indirect consequence of hypoxic events like carbon monoxide poisoning and narcotic drug overdose. To our best knowledge, there are no documented cases in literature of choreoathetosis and dementia following poppy-induced DPHL with 14-3-3 protein in cerebrospinal fluid (CSF). Case presentation: We report the case of a 70-year-old female who underwent cardiopulmonary resuscitation (CPR) due to overdose of homemade refined opium poppy paste two weeks prior to presentation. She presented a progressive cognitive decline, along with the development of apraxia and choreic movement affecting her tongue and bilateral upper and lower extremities. During the symptomatic phase, brain magnetic resonance imaging (MRI) showed bilateral symmetrical hyperintense signals mostly in central frontal, temporal, and parieto-occipital lobes in the diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences which are the characteristic findings of DPHL. CSF routine analysis, as well as toxicology screening, autoimmune and paraneoplastic encephalitis panels were negative, but the presence of 14-3-3 protein in the CSF was detected. With steroid therapy, hyperbaric oxygen therapy and symptomatic treatment, she experienced gradual improvement in cognition, motivation, and psychomotor function. Conclusion: DPHL represents a distinct form of encephalopathy characterized by unique clinical course and imaging features. It is the first report of DPHL with positive 14-3-3 protein in CSF. The potential of 14-3-3 protein as a biomarker for diagnosing DPHL and its ability to predict disease severity and prognosis warrants further research.

Subjective cognitive and olfactory impairments predict different prospective dementia outcomes.

Self-reported measures emerge as potential indicators for early detection of dementia and mortality. We investigated the predictive value of different self-reported measures, including subjective cognitive decline (SCD), subjective olfactory impairment (SOI), subjective taste impairment (STI) and self-reported poor health (SPH), in order to determine the risk of progressing to Alzheimer's Disease (AD) dementia, Parkinson's Disease (PD) dementia or any-other-cause dementia. A total of 6028 cognitively unimpaired individuals from the 8th-wave of the English Longitudinal Study of Ageing (ELSA) were included as baseline sample, and 5297 individuals from the 9th-wave were included as two-year follow-up sample. Self-rated measures were assessed using questions from the ELSA structured interview. Three logistic regression models were fitted to predict different the dementia outcomes. SCD based on memory complaints (OR = 11.145; p < 0.001), and older age (OR = 1.108, p < 0.001) significantly predicted the progression to AD dementia at follow-up. SOI (OR = 7.440; p <0.001) and older age (OR = 1.065, p = 0.035) significantly predicted the progression to PD dementia at follow-up. Furthermore, SCD based on memory complaints (OR = 4.448; p < 0.001) jointly with complaints in other (non-memory) mental abilities (OR = 6.662; p < 0.001), and older age (OR = 1.147, p < 0.001) significantly predicted the progression to dementia of any other cause. Different types of complaints are specifically associated with different dementia outcomes. Our study demonstrates that self-reported measures are a useful and accessible tool when screening for individuals at risk of dementia in the general population.

ZiBu PiYin Recipe Regulates Central and Peripheral Aß Metabolism and Improves Diabetes-associated Cognitive Decline in ZDF Rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cognitive impairment caused by central neuropathy in type 2 diabetes mellitus (T2DM), namely diabetes-associated cognitive decline (DACD), is one of the common complications in patients with T2DM. Studies have shown that brain ß-amyloid (Aß) deposition is a typical pathological change in patients with DACD, and that there is a close relationship between intestinal microorganisms and cognitive impairment. However, the specific mechanism(s) of alteration in Aß metabolism in DACD, and of the correlation between Aß metabolism and intestinal microorganisms remain unknown. AIM OF THE STUDY: Revealing the mechanism of ZBPYR regulating Aß metabolism and providing theoretical basis for clinical evaluation and diagnosis of DACD. MATERIALS AND METHODS: We characterized Aß metabolism in the central and peripheral tissues of Zucker diabetic fatty (ZDF) rats with DACD, and then explored the preventive and therapeutic effects of ZiBu PiYin Recipe (ZBPYR). Specifically, we assessed these animals for the formation, transport, and clearance of Aß; the morphological structure of the blood-brain barrier (BBB); and the potential correlation between Aß metabolism and intestinal microorganisms. RESULTS: ZBPYR provided improvements in the structure of the BBB, attenuation of Aß deposition in the central and peripheral tissues, and a delay in the development of DACD by improving the expression of Aß production, transport, and clearance related protein in ZDF rats. In addition, ZBPYR improved the diversity and composition of intestinal microorganisms, decreased the abundance of Coprococcus, a bacterium closely related to Aß production, and up regulate the abundance of Streptococcus, a bacterium closely related to Aß clearance. CONCLUSION: The mechanism of ZBPYR ability to ameliorate DACD may be closely related to changes in the intestinal microbiome.

Blood pressure, brain lesions and cognitive decline in patients with atrial fibrillation.

Background: The influence of atrial fibrillation (AF) and blood pressure (BP) on brain lesions and cognitive function is unclear. We aimed to investigate the association of BP with different types of brain lesions and cognitive decline in patients with AF. Methods: Overall, 1,213 AF patients underwent standardized brain magnetic resonance imaging at baseline and after 2 years, as well as yearly neurocognitive testing. BP was measured at baseline and categorized according to guidelines. New lesions were defined as new or enlarged brain lesions after 2 years. We defined cognitive decline using three different neurocognitive tests. Logistic and Cox regression analyses were performed to examine the associations of BP with new brain lesions and cognitive decline. Results: The mean age was 71 ± 8.4 years, 74% were male and mean BP was 135 ± 18/79 ± 12 mmHg. New ischemic lesions and white matter lesions were found in 5.4% and 18.4%, respectively. After multivariable adjustment, BP was not associated with the presence of new brain lesions after 2 years. There was no association between BP and cognitive decline over a median follow-up of 6 years when using the Montreal Cognitive Assessment or Digit Symbol Substitution Test. However, BP categories were inversely associated with cognitive decline using the Semantic Fluency Test, with the strongest association in patients with hypertension grade 1 [Hazard Ratio (95% Confidence Interval) 0.57(0.42 to 0.77)], compared to patients with optimal BP (p for linear trend: 0.025). Conclusions: In a large cohort of AF patients, there was no association between BP and incidence of brain lesions after 2 years. Also, there was no consistent association between BP and cognitive decline over a follow-up of 6 years. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02105844, Identifier (NCT02105844).

Masticatory Function, Sex, and Risk of Dementia Among Older Adults: A Population-Based Cohort Study.

BACKGROUND: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. METHODS: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. RESULTS: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. CONCLUSION: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.

Gender differences in neurocognitive assessments: insights from a pilot study with the International Neurocognitive Test Profile (INCP) digital battery.

BACKGROUND: The aging global population has led to an increase in the number of dementia diagnoses, with projections indicating a continued upward trend. This demographic change presents profound challenges for patients, their families, and healthcare systems worldwide. Consequently, the demand for reliable and user-friendly screening tools that can detect dementia at early stages and monitor its progression is more critical than ever. The International Neurocognitive Test Profile (INCP), developed at the Medical University of Vienna, aims to address this need by offering a digital test battery for the early detection of dementia. This study forms a part of the INCP's ongoing development and evaluation, specifically investigating the influence of gender on test outcomes. METHODS: Seventy participants, recruited through flyers at the Vienna General Hospital, completed the INCP assessment using tablets as part of the study. The effect of gender on performance across various INCP subtests was analyzed using Mann-Whitney U tests. For further exploratory analysis, a correlation matrix was calculated encompassing demographic variables (age and education), screening data, and all INCP subtests. RESULTS: The analysis revealed significant gender differences in two INCP subtests related to executive functions. Males outperformed females on the Figure Fluency Test (r = 0.30, indicating a moderate effect) and the Dice 2­n Back Test (r = 0.29, indicating a small effect). However, when correcting for multiple comparisons, no significant gender disparities were observed in the scores of the subtests. CONCLUSION: The identification of possible gender differences in specific subtests underscores the importance of considering gender as a variable in the further development and evaluation of the INCP. These findings offer valuable insights for the design and planning of future studies involving the INCP.

VGLUT2 may improve cognitive function in depressed rats by protecting prefrontal cortex neurons.

Objective: Depression may be accompanied by cognitive impairment, but its pathogenesis remains unclear. This study aims to investigate the protective effects of fluoxetine on behavioral performance and prefrontal cortex neuronal damage in rats with depression-associated cognitive impairment, based on the observation of VGLUT2 protein expression. Methods: Forty-five SPF-grade male SD rats were randomly divided into three groups (n = 15): normal control group (CON), depression group (DD), and fluoxetine group (DD + F). The CON group was reared normally, while the DD and DD + F groups underwent chronic unpredictable mild stress (CUMS) combined with social isolation to induce a depression-related cognitive dysfunction model. After modeling, the DD + F group was treated with fluoxetine (10 mg/kg, ig) for 14 days. Behavioral tests were performed to assess changes in mood, cognition, learning, and social abilities. Histopathological observations were made to examine pathological changes, neuronal apoptosis, ultrastructure, and dendritic spine density in the prefrontal cortex. The concentration, relative expression level, and mRNA expression of VGLUT2 protein were also measured. Finally, a correlation analysis was performed between the relative expression level and mRNA expression of VGLUT2 protein and the pathological changes in neurons. Results: Compared to the CON group, the DD group exhibited decreased body weight, anhedonia, increased behavioral despair, reduced locomotor activity and spontaneous exploratory behavior, impaired spatial learning and memory, and decreased social interaction and social cognitive ability. Pathological damage was observed in the prefrontal cortex, with neuronal apoptosis, ultrastructural damage, and reduced neuroplasticity. The concentration, relative expression, and mRNA expression levels of VGLUT2 protein were decreased. Following fluoxetine intervention, the above behavioral phenotypes improved; pathological damage showed varying degrees of recovery; and the concentration, relative expression, and mRNA expression levels of VGLUT2 protein increased. Finally, there was a significant correlation between VGLUT2 protein expression and pathological changes in the prefrontal cortex. Conclusion: After 28 days of CUMS combined with isolation rearing, rats exhibited impairments in mood, cognition, learning, and social abilities, with neuronal damage and decreased VGLUT2 protein levels in the prefrontal cortex. Following fluoxetine intervention, VGLUT2 protein expression increased, neuronal repair in the prefrontal cortex occurred, depressive-like behavior improved, and cognitive learning and social abilities were restored.

Racial discrimination predicts subjective cognitive decline: Perceived relationship support buffers the association.

OBJECTIVES: Recent studies show that chronic exposure to racial discrimination increases the occurrence of subjective cognitive decline (SCD) among Black Americans. Little research, however, has examined potential for protective factors, such as perceived partner support, to buffer these effects. METHODS: This study utilized longitudinal data over a 10-year period from the Family and Community Health Study (FACHS) to examine the associations between experiences of racial discrimination, marital status, partner support, and SCD, measured by the Everyday Cognition (ECog) Scale, among 286 middle-aged Black American women. Regression analysis and internal moderator analyses were employed to analyze the data. RESULTS: About 31% were in married relationships. Thirty-four percent reported cognitive decline, especially in forgetting object locations and dates. Chronic discrimination predicted SCD, and for those in couple relationships, partner support buffered the adverse effects of discrimination, with those in warm and supportive relationships experiencing less SCD than those in relatively unsupportive relationships or not in a relationship. CONCLUSIONS: The study's findings support the idea that racism influences SCD and underscores the importance of supportive couple relationships in promoting resilience. The results also highlight the potential value of culturally relevant family interventions and support strategies to reduce the impact of discrimination-induced stress on cognitive health.

Independent and joint associations of cardiometabolic multimorbidity and depression on cognitive function: findings from multi-regional cohorts and generalisation from community to clinic.

Background: Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings in additional settings, including clinical. Methods: Data harmonization was performed across 14 longitudinal cohort studies within the Cohort Studies of Memory in an International Consortium (COSMIC) group, spanning North America, South America, Europe, Africa, Asia, and Australia. Three external validation studies with distinct settings were employed for generalization. Participants were eligible for inclusion if they had data for CMM and were free of dementia at baseline. Baseline CMM was defined as: 1) CMM 5, ≥2 among hypertension, hyperlipidemia, diabetes, stroke, and heart disease and 2) CMM 3 (aligned with previous studies), ≥2 among diabetes, stroke, and heart disease. Baseline depression was primarily characterized by binary classification of depressive symptom measurements, employing the Geriatric Depression Scale and the Center for Epidemiological Studies-Depression scale. Global cognition was standardized as z-scores through harmonizing multiple cognitive measures. Longitudinal cognition was calculated as changes in global cognitive z-scores. A pooled individual participant data (IPD) analysis was utilized to estimate the independent and joint associations of CMM and depression on cognitive outcomes in COSMIC studies, both cross-sectionally and longitudinally. Repeated analyses were performed in three external validation studies. Findings: Of the 32,931 older adults in the 14 COSMIC cohorts, we included 30,382 participants with complete data on baseline CMM, depression, and cognitive assessments for cross-sectional analyses. Among them, 22,599 who had at least 1 follow-up cognitive assessment were included in the longitudinal analyses. The three external studies for validation had 1964 participants from 3 multi-ethnic Asian older adult cohorts in different settings (community-based, memory clinic, and post-stroke study). In COSMIC studies, each of CMM and depression was independently associated with cross-sectional and longitudinal cognitive function, without significant interactions between them (Ps > 0.05). Participants with both CMM and depression had lower cross-sectional cognitive performance (e.g. ß = -0.207, 95% CI = (-0.255, -0.159) for CMM5 (+)/depression (+)) and a faster rate of cognitive decline (e.g. ß = -0.040, 95% CI = (-0.047, -0.034) for CMM5 (+)/depression (+)), compared with those without either condition. These associations remained consistent after additional adjustment for APOE genotype and were robust in two-step random-effects IPD analyses. The findings regarding the joint association of CMM and depression on cognitive function were reproduced in the three external validation studies. Interpretation: Our findings highlighted the importance of investigating age-related co-morbidities in a multi-dimensional perspective. Targeting both cardiometabolic and psychological conditions to prevent cognitive decline could enhance effectiveness. Funding: Natural Science Foundation of China and National Institute on Aging/National Institutes of Health.

Maresin 1 alleviates neuroinflammation and cognitive decline in a mouse model of cecal ligation and puncture. / Maresin 1å‡è½»ç›²è‚ ç»“æ‰Žç©¿å­”å°é¼ æ¨¡åž‹ä¸­çš„ç¥žç»ç‚Žç—‡å’Œè®¤çŸ¥å‡é€€ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy. This study aims to explore the effects of maresin 1 (MaR1), an anti-inflammatory and pro-resolving lipid mediator, on sepsis-induced neuroinflammation and cognitive impairment. METHODS: Mice were randomly assigned to 4 groups: A sham group (sham operation+vehicle), a cecal ligation and puncture (CLP) group (CLP operation+vehicle), a MaR1-LD group (CLP operation+1 ng MaR1), and a MaR1-HD group (CLP operation+10 ng MaR1). MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation, then every other day for 7 days. Survival rates were monitored, and serum inflammatory cytokines [tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6] were measured 24 h after operation using enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed 7 days after operation using the Morris water maze (MWM) test and novel object recognition (NOR) task. The mRNA expression of TNF-α, IL-1ß, IL-6, inducible nitric oxide synthase (iNOS), IL-4, IL-10, and arginase 1 (Arg1) in cortical and hippocampal tissues was determined by real-time reverse transcription PCR (RT-PCR). Western blotting was used to determine the protein expression of iNOS, Arg1, signal transducer and activator of transcription 6 (STAT6), peroxisome proliferator-activated receptor gamma (PPARγ), and phosphorylated STAT6 (p-STAT6) in hippocampal tissue. Microglia activation was visualized via immunofluorescence. Mice were also treated with the PPARγ antagonist GW9662 to confirm the involvement of this pathway in MaR1's effects. RESULTS: CLP increased serum levels of TNF-α, IL-1ß, and IL-6, and reduced body weight and survival rates (all P<0.05). Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α, IL-1ß, and IL-6 levels, improved body weight, and increased survival rates (all P<0.05). No significant difference in efficacy was observed between the 2 doses (all P>0.05). MWM test and NOR task indicated that CLP impaired spatial learning, which MaR1 mitigated. However, GW9662 partially reversed MaR1's protective effects. Real-time RT-PCR results demonstrated that, compared to the sham group, mRNA expression of TNF-α, IL-1ß, and iNOS significantly increased in hippocampal tissues following CLP (all P<0.05), while IL-4, IL-10, and Arg1 showed a slight decrease, though the differences were not statistically significant (all P>0.05). Compared to the CLP group, both 1 ng and 10 ng MaR1 decreased TNF-α, IL-1ß, and iNOS mRNA expression in hippocampal tissues and increased IL-4, IL-10, and Arg1 mRNA expression (all P<0.05). Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group (P<0.05). Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group (both P<0.05). Western blotting results showed that, compared to the CLP group, both 1 ng and 10 ng MaR1 down-regulated the iNOS expression, while up-regulated the expression of Arg1, PPARγ, and p-STAT6 (all P<0.05). However, the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγ compared to the MaR1-LD group (all P<0.05). CONCLUSIONS: MaR1 inhibits the classical activation of hippocampal microglia, promotes alternative activation, reduces sepsis-induced neuroinflammation, and improves cognitive decline.

Resting-state functional connectivity abnormalities in subjective cognitive decline: A 7T MRI study.

Resting-state functional connectivity (FC) MRI is sensitive to brain changes in Alzheimer's disease in preclinical stages, however studies in persons with subjective cognitive decline (SCD) have reported conflicting findings, and no study is available at 7T MRI. In this study, we investigated FC alterations in sixty-six participants recruited at the Geneva Memory Center (24 controls, 14 SCD, 28 cognitively impaired [CI]). Participants were classified as SCD if they reported cognitive complaints without objective cognitive deficits, and underwent 7T fMRI to assess FC in canonical brain networks and their association with cognitive/clinical features. SCD showed normal cognition, a trend for higher depressive symptoms, and normal AD biomarkers. Compared to the other two groups, SCD showed higher FC in frontal default mode network (DMN) and insular and superior temporal nodes of ventral attention network (VAN). Higher FC in the DMN and VAN was associated with worse cognition but not depression, suggesting that hyper-connectivity in these networks may be a signature of age-related cognitive decline in SCD at low risk of developing AD.

Progressive cervical cord atrophy parallels cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive episodic memory dysfunction. A prominent hallmark of AD is gradual brain atrophy. Despite extensive research on brain pathology, the understanding of spinal cord pathology in AD and its association with cognitive decline remains understudied. We analyzed serial magnetic resonance imaging (MRI) scans from the ADNI data repository to assess whether progressive cord atrophy is associated with clinical worsening. Cervical cord morphometry was measured in 45 patients and 49 cognitively normal controls (CN) at two time points over 1.5 years. Regression analysis examined associations between cord atrophy rate and cognitive worsening. Cognitive and functional activity performance declined in patients during follow-up. Compared with controls, patients showed a greater rate of decline of the anterior-posterior width of the cross-sectional cord area per month (- 0.12%, p = 0.036). Worsening in the mini-mental state examination (MMSE), clinical dementia rating (CDR), and functional assessment questionnaire (FAQ) was associated with faster rates of cord atrophy (MMSE: r = 0.320, p = 0.037; CDR: r = - 0.361, p = 0.017; FAQ: r = - 0.398, p = 0.029). Progressive cord atrophy occurs in AD patients; its rate over time being associated with cognitive and functional activity decline.

Self- and study partner-reported cognitive decline in older adults without dementia: The role of α-synuclein and amyloid biomarkers in the Alzheimer's Disease Neuroimaging Initiative.

INTRODUCTION: Subjective cognitive decline (SCD) may be an early marker of Alzheimer's disease (AD) pathology. Until recently, it was impossible to measure biomarkers specific for α-synuclein pathology; therefore, its association with subjective reports of cognitive decline is unknown. METHODS: Alzheimer's Disease Neuroimaging Initiative participants without dementia (n = 918) were classified as positive or negative for amyloid beta (Aß+ or Aß-) and α-synuclein (α-syn+ or α-syn-) biomarkers. Self- and study partner-reported cognitive decline was measured with the Everyday Cognition (ECog) questionnaire. RESULTS: Per self-report, Aß+/α-syn+ had the greatest cognitive decline. Aß-/α-syn+ did not differ from Aß-/α-syn- across ECog scores. Study partner-reported results had a similar pattern, but Aß+/α-syn- and Aß+/α-syn+ did not differ across ECog scores. Mild cognitive impairment classification moderated the study partner-reported memory score. DISCUSSION: While α-syn+ alone did not increase subjective reports of cognitive decline, Aß+/α-syn+ had the most self- and study partner-rated cognitive decline. Therefore, the presence of multiple pathologies was associated with greater SCD. HIGHLIGHTS: Cerebrospinal fluid α-synuclein (α-syn) seed amplification assay was used to determine α-syn positivity. Amyloid beta (Aß)-/α-syn-, Aß-/α-syn+, Aß+/α-syn-, and Aß+/α-syn+ biomarker groups were created. Aß+/α-syn+ had greater subjective cognitive decline (SCD) than the other biomarker groups. Aß-/α-syn+ did not differ from Aß-/α-syn- across self- or study-partner reported SCD scores. Study partner-reported subjective memory results were largely driven by participants with mild cognitive impairment.

Corrigendum: Neurocognitive health in LGBTQIA+ older adults: current state of research and recommendations.

[This corrects the article DOI: 10.3389/fnhum.2024.1394374.].

Associations of socioeconomic status and healthy lifestyle with incident dementia and cognitive decline: two prospective cohort studies.

Background: Little is known about the complex associations of socioeconomic status (SES) and healthy lifestyle with cognitive dysfunction. Methods: Using data from the Health and Retirement Study (HRS) [2008-2020] and the English Longitudinal Study of Ageing (ELSA) [2004-2018], SES was constructed by latent class analysis using education level, total household income and wealth. Overall healthy lifestyle was derived using information on never smoking, low to moderate alcohol consumption (drinks/day: (0, 1] for women and (0, 2] for men), top tertile of physical activity, and active social contact. Findings: A total of 12,437 and 6565 participants from the HRS and ELSA were included (40.8% and 46.0% men and mean age 69.3 years and 65.1 years, respectively). Compared with participants of high SES, those of low SES had higher risk of incident dementia (hazard ratio 3.17, 95% confidence interval 2.72-3.69 in the HRS; 1.43, 1.09-1.86 in the ELSA), and the proportions mediated by overall lifestyle were 10.4% (7.3%-14.6%) and 2.7% (0.5%-14.0%), respectively. Compared with participants of high SES and favorable lifestyle, those with low SES and unfavorable lifestyle had a higher risk of incident dementia (4.27, 3.40-5.38 in the HRS; 2.02, 1.25-3.27 in the ELSA) and accelerated rate of global cognitive decline (ß = -0.058 SD/year; 95% CI: -0.073, -0.043 in the HRS; ß = -0.049 SD/year; 95% CI: -0.063, -0.035 in the ELSA). Interpretation: Unhealthy lifestyle only mediated a small proportion of the socioeconomic inequality in dementia risk in both US and UK older adults. Funding: This work was supported by grants from the National Natural Science Foundation of China (82088102 and 82370819), the National Key R&D Program of China (2023YFC2506700), the Shanghai Municipal Government (22Y31900300), the Shanghai Clinical Research Center for Metabolic Diseases (19MC1910100), the Innovative Research Team of High-Level Local Universities in Shanghai, the Special Project for Clinical Research in Health Industry of Shanghai Municipal Health Commission (202340084), and Ruijin Hospital Youth Incubation Project (KY20240805). Y.X. is supported by the National Top Young Talents program.

Assessing the Potential of EEG in Early Detection of Alzheimer's Disease: A Systematic Comprehensive Review (2000-2023).

Background: As the prevalence of Alzheimer's disease (AD) grows with an aging population, the need for early diagnosis has led to increased focus on electroencephalography (EEG) as a non-invasive diagnostic tool. Objective: This review assesses advancements in EEG analysis, including the application of machine learning, for detecting AD from 2000 to 2023. Methods: Following PRISMA guidelines, a search across major databases resulted in 25 studies that met the inclusion criteria, focusing on EEG's application in AD diagnosis and the use of novel signal processing and machine learning techniques. Results: Progress in EEG analysis has shown promise for early AD identification, with techniques like Hjorth parameters and signal compressibility enhancing detection capabilities. Machine learning has improved the precision of differential diagnosis between AD and mild cognitive impairment. However, challenges in standardizing EEG methodologies and data privacy remain. Conclusions: EEG stands out as a valuable tool for early AD detection, with the potential to integrate into multimodal diagnostic approaches. Future research should aim to standardize EEG procedures and explore collaborative, privacy-preserving research methods.

Association between blood-based protein biomarkers and brain MRI in the Alzheimer's disease continuum: a systematic review.

Blood-based biomarkers (BBM) are becoming easily detectable tools to reveal pathological changes in Alzheimer's disease (AD). A comprehensive and up-to-date overview of the association between BBM and brain MRI parameters is not available. This systematic review aimed to summarize the literature on the associations between the main BBM and MRI markers across the clinical AD continuum. A systematic literature search was carried out on PubMed and Web of Science and a total of 33 articles were included. Hippocampal volume was positively correlated with Aß42 and Aß42/Aß40 and negatively with Aß40 plasma levels. P-tau181 and p-tau217 concentrations were negatively correlated with temporal grey matter volume and cortical thickness. NfL levels were negatively correlated with white matter microstructural integrity, whereas GFAP levels were positively correlated with myo-inositol values in the posterior cingulate cortex/precuneus. These findings highlight consistent associations between various BBM and brain MRI markers even in the pre-clinical and prodromal stages of AD. This suggests a possible advantage in combining multiple AD-related markers to improve accuracy of early diagnosis, prognosis, progression monitoring and treatment response.

Social reward and nonsocial reward processing across the adult lifespan: An interim multi-echo fMRI and diffusion dataset.

Social relationships change across the lifespan as social networks narrow and motivational priorities shift. These changes may affect, or reflect, differences in how older adults make decisions related to processing social and non-social rewards. While we have shown initial evidence that older adults have a blunted response to some features of social reward, further work in larger samples is needed to replicate our results and probe the extent to which age-related differences translate to real world consequences, such as financial exploitation. To address this gap, we are conducting a 5-year study funded by the National Institute on Aging (NIH R01-AG067011). Over the course of the funding period (2021-2026), this study seeks to: 1) characterize neural responses to social rewards across adulthood; 2) relate those responses to risk for financial exploitation and sociodemographic factors tied to risk; and 3) examine changes in risk for financial exploitation over time in healthy and vulnerable groups of older adults. This paper describes the preliminary release of data for the larger study. Adults (N = 114; 40 male / 70 female / 4 other or non-binary; 21-80 years of age M = 42.78, SD = 17.13) were recruited from the community to undergo multi-echo fMRI while completing tasks that measure brain function during social reward and decision making. Tasks probe neural response to social reward (e.g., peer vs. monetary feedback) and social context and closeness (e.g., sharing a monetary reward with a friend compared to a stranger). Neural response to social decision making is probed via economic trust and ultimatum games. Functional data are complimented by a T1 weighted anatomical scan and multi-shell diffusion-weighted imaging (DWI) to enable tractography and assess neurite orientation dispersion and density. Overall, this dataset has extensive potential for re-use, including leveraging multimodal neuroimaging data, within subject measures of fMRI data from different tasks - data features that are rarely seen in an adult lifespan dataset. Finally, the functional data will allow for developmentally sensitive cross-sectional analyses of differences in brain response to nuanced differences in reward contexts and outcomes (e.g., monetary vs. social; sharing winnings with a friend vs. stranger; stranger vs. computer).

Motoric cognitive risk syndrome as a predictive factor of cognitive impairment and dementia - A systematic review and meta-analysis.

BACKGROUND: Motoric cognitive risk syndrome (MCR) is defined as the presence of slow gait-speed and subjective cognitive decline in older individuals without mobility disability or dementia. While some studies suggest that MCR is a pre-dementia syndrome and may help predict the risk of cognitive impairment and dementia, not all studies concur. The objective of this study is to comprehensively summarize and synthesize evidence to assess the association between MCR and cognitive impairment and dementia. METHODS: Following a pre-specified protocol, two authors systematically searched PubMed, Embase, and The Cochrane Library from inception to 19 August 2024 for observational or randomized studies pertaining to the association between MCR and cognitive impairment and dementia. We favoured maximally adjusted hazards and odds ratios to determine the longitudinal and cross-sectional risk of cognitive impairment and dementia. We investigated for potential sources of heterogeneity and also conducted sensitivity and subgroup analyses by continent and the type of cognitive outcome. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. RESULTS: We included 20 studies comprising a combined cohort of 1206,782 participants, of which 17 studies were included in the quantitative analysis. The pooled analysis outlined that individuals with MCR exhibited 2.20-fold higher risk of cognitive impairment and dementia, compared to controls (RR=2.20; 95 %CI=1.91-2.53). These findings remained robust across all subgroup analyses, sensitivity analyses and assessments of publication bias. CONCLUSION: MCR may be considered a predictive factor for long-term cognitive impairment and dementia. This should be taken into consideration when clinically evaluating the risk of cognitive impairment and dementia but further research is required to lend greater clarity to this association.

Fecal microbiota transplantation derived from mild cognitive impairment individuals impairs cerebral glucose uptake and cognitive function in wild-type mice: Bacteroidetes and TXNIP-GLUT signaling pathway.

Gut microbiome dysbiosis has been widely implicated in cognitive impairment, but the identity of the specific bacterial taxa and mechanisms are not fully elucidated. Brain glucose hypometabolism coincides with the cognitive decline. This study explored the link among cognition, gut microbiota and glucose uptake based on the fecal microbiota transplantation from mild cognitive impairment individuals (MCI-FMT) and investigated whether similar mechanisms were involved in 27-hydroxycholesterol (27-OHC)-induced cognitive decline. Our results showed that the MCI-FMT mice exhibited learning and memory decline and morphological lesions in the brain and colon tissues. There were reduced 18F-fluorodeoxyglucose uptake, downregulated expression of glucose transporters (GLUT1,3,4) and upregulated negative regulator of glucose uptake (TXNIP) in the brain. MCI-FMT altered the bacterial composition and diversity of the recipient mice, and the microbial signatures highlighted by the increased abundance of Bacteroides recapitulated the negative effects of MCI bacterial colonization. However, inhibiting Bacteroidetes or TXNIP increased the expression of GLUT1 and GLUT4, significantly improving brain glucose uptake and cognitive performance in 27-OHC-treated mice. Our study verified that cognitive decline and abnormal cerebral glucose uptake were associated with gut microbiota dysbiosis; we also revealed the involvement of Bacteroidetes and molecular mechanisms of TXNIP-related glucose uptake in cognitive deficits caused by 27-OHC.