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1.
Nat Commun ; 15(1): 5003, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937442

RESUMO

Studies examining lifestyle and cognitive decline often use healthy lifestyle indices, making it difficult to understand implications for interventions. We examined associations of 16 lifestyles with cognitive decline. Data from 32,033 cognitively-healthy adults aged 50-104 years participating in prospective cohort studies of aging from 14 European countries were used to examine associations of lifestyle with memory and fluency decline over 10 years. The reference lifestyle comprised not smoking, no-to-moderate alcohol consumption, weekly moderate-plus-vigorous physical activity, and weekly social contact. We found that memory and fluency decline was generally similar for non-smoking lifestyles. By contrast, memory scores declined up to 0.17 standard deviations (95% confidence interval= 0.08 - 0.27) and fluency scores up to 0.16 standard deviations (0.07 - 0.25) more over 10 years for those reporting smoking lifestyles compared with the reference lifestyle. We thus show that differences in cognitive decline between lifestyles were primarily dependent on smoking status.


Assuntos
Consumo de Bebidas Alcoólicas , Disfunção Cognitiva , Estilo de Vida Saudável , Fumar , Humanos , Pessoa de Meia-Idade , Europa (Continente)/epidemiologia , Idoso , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Idoso de 80 Anos ou mais , Fumar/epidemiologia , Estudos Prospectivos , Consumo de Bebidas Alcoólicas/epidemiologia , Exercício Físico , Memória/fisiologia , Envelhecimento/fisiologia , Cognição/fisiologia , Estilo de Vida
2.
Sci Rep ; 14(1): 14800, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926515

RESUMO

Web-based testing of cognitive abilities allows for large-scale assessments without geographical constraints. Yet, the extent to which it can reach populations beyond the typical demographic groups recruited for cognitive studies is unclear. This study focused on comparing the characteristics of individuals from a general population study (HUNT4) who chose to participate in a cognitive study (HUNT4-Hjernetrim) with those who did not. Additionally, we investigated participants' engagement and user experience. We obtained data on socio-demographics, health conditions (both physical and mental), self-reported cognitive or learning difficulties, and lifestyle factors of Hjernetrim participants and non-participants from the HUNT4 database. Hjernetrim involved 13 cognitive tests, administered through the online platform Memoro. We used logistic regressions to assess participation biases and linear regressions to assess participants' engagement and user experience. Of 65,851 HUNT4 participants invited via regular mail to Hjernetrim, 5634 (9.4%, aged 13-97, 54% women) participated. The best represented in the sample were 50-79-year-olds, women, tertiary educated, living alone, from urban areas, not occupationally active, and reporting memory complaints. Individuals who were aged 80+, had motor or vision impairments, and teenagers with learning disabilities, were underrepresented. Participants were more likely to have mental health problems, have or survived cancer and less likely to have cardiovascular disease. Participants logged on mainly during weekdays, the preferred time of day varied by age. On average, participants used 42 min and completed 78% of the tasks. Using PCs provided the most complete data. In terms of user experiences, 65% were positive while 14% were negative or reported technical difficulties. Overall, the study demonstrated that web-based methodology allowed for a relatively well-represented sample that included groups typically difficult to reach. The presence of somatic and mental diseases had a variable influence on participation. Participants finished most tests and reported positive experiences overall.


Assuntos
Cognição , Internet , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Cognição/fisiologia , Adolescente , Idoso de 80 Anos ou mais , Adulto Jovem , Testes Neuropsicológicos
3.
Alzheimers Res Ther ; 16(1): 135, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926747

RESUMO

BACKGROUND: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. METHODS: Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA1c), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions. RESULTS: The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3-20.8) years. When examining independent effects, APOE ε4 genotype(p < 0.01), and higher HbA1c(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA1c(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers(p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI(p < 0.05) and ɛ2-carriers with higher HbA1c-levels(p < 0.05). CONCLUSIONS: Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.


Assuntos
Função Executiva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Seguimentos , Estudos Prospectivos , Suécia/epidemiologia , Função Executiva/fisiologia , Cognição/fisiologia , Atenção/fisiologia , Índice de Massa Corporal , Memória/fisiologia , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/análise , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/genética , Genótipo , Apolipoproteína E4/genética , Testes Neuropsicológicos , Disfunção Cognitiva/genética , Disfunção Cognitiva/epidemiologia
4.
Medicine (Baltimore) ; 103(23): e38500, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847667

RESUMO

This study aimed to investigate the different impacts of sensorial and mobility frailty on overall and domain-specific cognitive function. Further, the independent associations between other intricate capacity (IC) dimensions, including vitality and psychological dimensions, and overall and domain-specific cognitive function were investigated. A total of 429 participants (mean age, 72.91 ±â€…7.014 years; 57.30% female) underwent IC capacity assessment. Other covariates, such as demographics, health-related variables were also assessed. Overall or domain-specific cognitive impairment was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychosocial confounders. After adjustment for demographic, health-related, and psychosocial confounders, individuals with sensorial frailty (odds ratio [OR] = 0.435; 95% confidence interval [CI] = 0.236-0.801; P = .008) had a significantly lower risk of mild cognitive impairment (MCI), marginally low delayed memory impairment (OR = 0.601, 95% CI = 0.347-1.040; P = .069), and language impairment (OR = 0.534, 95% CI = 0.305-0.936; OR = 0.318, P = .029; OR = 0.318,95% CI = 0.173-0.586; P < .001) by Boston naming and animal fluency tests than did those with both sensorial and mobility frailty or mobility frailty only. Depressive symptoms had a significant negative influence on executive function. Cardiovascular disease and non-skin malignancy were independent determinants of MCI, and diabetes mellitus was independently associated with processing speed, attention, and executive function. Sensorial and mobility frailty were independent risk factors for cognitive impairment. Mobility frailty had a greater negative influence on the overall cognitive function and memory and language function than did sensorial frailty. The reserve decline in the psychological dimension of IC and chronic diseases also had a significant adverse influence on overall and domain-specific cognition function.


Assuntos
Cognição , Disfunção Cognitiva , Fragilidade , Vida Independente , Humanos , Feminino , Masculino , Idoso , Disfunção Cognitiva/epidemiologia , China/epidemiologia , Cognição/fisiologia , Fragilidade/psicologia , Idoso Fragilizado/psicologia , Idoso Fragilizado/estatística & dados numéricos , Idoso de 80 Anos ou mais , Avaliação Geriátrica/métodos , Estudos Transversais , Limitação da Mobilidade , População do Leste Asiático
5.
J Orthop Surg Res ; 19(1): 361, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890731

RESUMO

BACKGROUND: Near infrared brain functional imaging (FNIRS) has been used for the evaluation of brain functional areas, the imaging differences of central activation of cognitive-motor dual tasks between patients with chronic lateral ankle instability (CLAI) and healthy population remain unclear. This study aimed to evaluated the role of central imaging based on FNIRS technology on the plan management in patients with CLAI, to provide insights to the clinical treatment of CLAI. METHODS: CLAI patients treated in our hospital from January 1, 2021 to June 31, 2022 were selected. Both CLAI patients and health controls were intervened with simple task and cognitive-motor dual task under sitting and walking conditions, and the changes of oxygenated hemoglobin concentration in bilateral prefrontal cortex (PFC), premotor cortex (PMC) and auxiliary motor area (SMA) were collected and compared. RESULTS: A total of 23 participants were enrolled. There were significant differences in the fNIRS ΔHbO2 of barefoot subtractive walking PFC-R and barefoot subtractive walking SMA-R between experimental and control group (all P < 0.05). There was no significant difference in ΔHbO2 between the experimental group and the control group in other states (P > 0.05). There was no significant difference in ΔHbO2 between the experimental group and the control group in each state of the brain PMC region. CONCLUSION: Adaptive alterations may occur within the relevant brain functional regions of individuals with CLAI. The differential activation observed between the PFC and the SMA could represent a compensatory mechanism emerging from proprioceptive afferent disruptions following an initial ankle sprain.


Assuntos
Instabilidade Articular , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Feminino , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/fisiopatologia , Masculino , Adulto , Doença Crônica , Adulto Jovem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/fisiopatologia , Caminhada/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Cognição/fisiologia
6.
Sci Rep ; 14(1): 12680, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902275

RESUMO

17ß-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain 18F-fluoroestradiol (18F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women's health.


Assuntos
Envelhecimento , Encéfalo , Cognição , Tomografia por Emissão de Pósitrons , Receptores de Estrogênio , Humanos , Feminino , Pessoa de Meia-Idade , Cognição/fisiologia , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Envelhecimento/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Estradiol/sangue , Estradiol/metabolismo , Sistemas Neurossecretores/metabolismo , Menopausa/metabolismo
7.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 66-72, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836680

RESUMO

This study aimed to investigate the mechanism of the effect of TREM2 on cognitive function in autistic mice. TREM2 overexpression and knockdown viruses were given to autism spectrum disorder (ASD) mice and BV2 microglia cell line. To assess cognitive performance, all groups of mice took part in the open field, new object recognition, Morris water maze, and three-box social experiments. Double immunofluorescence labeling demonstrated co-localization of LC3II and NeuN. Proteins from the PI3K/Akt/mTOR pathway were identified. In vivo, behavior studies revealed that TREM2 could successfully improve ASD mice's social interaction and cognitive performance. Besides, we discovered that TREM2 could increase autophagy in ASD mice. In vitro, overexpressing TREM2 reduced the expression of PI3K/AKT/mTOR pathway proteins, whereas knocking down TREM2 increased the expression of PI3K/AKT/mTOR pathway proteins. In conclusion, TREM2 could inhibit PI3K/Akt/mTOR signaling pathway, enhance autophagy, and improve the social communication ability and cognitive function of ASD mice.


Assuntos
Autofagia , Cognição , Glicoproteínas de Membrana , Microglia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores Imunológicos , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Cognição/fisiologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Microglia/metabolismo , Masculino , Transtorno Autístico/metabolismo , Transtorno Autístico/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/psicologia , Modelos Animais de Doenças , Comportamento Animal , Linhagem Celular , Camundongos Endogâmicos C57BL , Comportamento Social
8.
Neurology ; 103(1): e209534, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38857479

RESUMO

BACKGROUND AND OBJECTIVES: Epigenetic age estimators indicating faster/slower biological aging vs chronological age independently associate with several age-related outcomes; however, longitudinal associations with cognitive function are understudied. We examined associations of epigenetic age estimators with cognitive function measured annually. METHODS: This longitudinal study consisted of older women enrolled in the Women's Health Initiative Memory Study with DNA methylation (DNAm) collected at baseline (1995-1998) from 3 ancillary studies and were followed up to 13 years. Global cognitive function was measured annually by Modified Mini-Mental State Examination (3MS; baseline-2007) and by modified Telephone Interview for Cognitive Status (TICS-m, 2008-2021). We calculated 5 epigenetic age estimators: extrinsic AgeAccel, intrinsic AgeAccel, AgeAccelPheno, AgeAccelGrim2, Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), and AgeAccelGrim2 components (DNA-based plasma protein surrogates). We estimated longitudinal epigenetic age estimator-cognitive function associations using linear mixed-effects models containing age, education, race or ethnicity, and subsequently alcohol, smoking, body mass index, and comorbidities. We examined effect modification by APOE ε4 carriage. RESULTS: A total of 795 participants were enrolled. The mean baseline age was 70.8 ± 4 years (10.7% Black, 3.9% Hispanic or Latina, 85.4% White), A 1-SD (0.12) increment in DunedinPACE associated with faster annual declines in TICS-m scores in minimally adjusted (ß = -0.118, 95% CI -0.202 to -0.034; p = 0.0006) and fully adjusted (ß = -0.123, 95% CI -0.211 to -0.036; p = 0.006) models. AgeAccelPheno associated with faster annual declines in TICS-m with minimal adjustment (ß = -0.091, 95% CI -0.176 to -0.006; p = 0.035) but not with full adjustment. No other epigenetic age estimators associated with changes in 3MS or TICS-m. Higher values of DNAm-based surrogates of growth differentiation factor 15, beta-2 microglobulin, Cystatin C, tissue inhibitor metalloproteinase 1, and adrenomedullin associated with faster annual declines in 3MS and TICS-m. Higher DNAm log A1c associated with faster annual declines in TICS-m only. DunedinPACE associated with faster annual declines in 3MS among APOE ε4 carriers but not among noncarriers (p-interaction = 0.020). DISCUSSION: Higher DunedinPACE associated with faster declines in TICS-m and 3MS scores among APOE ε4 carriers. DunedinPACE may help identify older women at risk of future cognitive decline. Limitations include the ancillary studies that collected epigenetic data not designed to study epigenetics and cognitive function. We examined epigenetic age estimators with global cognitive function and not specific cognitive domains. Findings may not generalize to men and more diverse populations.


Assuntos
Envelhecimento , Cognição , Metilação de DNA , Epigênese Genética , Saúde da Mulher , Humanos , Feminino , Idoso , Estudos Longitudinais , Cognição/fisiologia , Envelhecimento/genética , Epigênese Genética/genética , Metilação de DNA/genética , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Memória/fisiologia
9.
J Neuroinflammation ; 21(1): 149, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840141

RESUMO

Uncontrolled neuroinflammation mediates traumatic brain injury (TBI) pathology and impairs recovery. Interleukin-6 (IL-6), a pleiotropic inflammatory regulator, is associated with poor clinical TBI outcomes. IL-6 operates via classical-signaling through membrane-bound IL-6 receptor (IL-6R) and trans-signaling through soluble IL-6 receptor (s)IL-6R. IL-6 trans-signaling specifically contributes to neuropathology, making it a potential precision therapeutic TBI target. Soluble glycoprotein 130 (sgp130) prevents IL-6 trans-signaling, sparing classical signaling, thus is a possible treatment. Mice received either controlled cortical impact (CCI) (6.0 ± 0.2 m/s; 2 mm; 50-60ms) or sham procedures. Vehicle (VEH) or sgp130-Fc was subcutaneously administered to sham (VEH or 1 µg) and CCI (VEH, 0.25 µg or 1 µg) mice on days 1, 4, 7, 10 and 13 post-surgery to assess effects on cognition [Morris Water Maze (MWM)] and ipsilateral hemisphere IL-6 related biomarkers (day 21 post-surgery). CCI + sgp130-Fc groups (0.25 µg and 1 µg) were combined for analysis given similar behavior/biomarker outcomes. CCI + VEH mice had longer latencies and path lengths to the platform and increased peripheral zone time versus Sham + VEH and Sham + sgp130-Fc mice, suggesting injury-induced impairments in learning and anxiety. CCI + sgp130-Fc mice had shorter platform latencies and path lengths and had decreased peripheral zone time, indicating a therapeutic benefit of sgp130-Fc after injury on learning and anxiety. Interestingly, Sham + sgp130-Fc mice had shorter platform latencies, path lengths and peripheral zone times than Sham + VEH mice, suggesting a beneficial effect of sgp130-Fc, independent of injury. CCI + VEH mice had increased brain IL-6 and decreased sgp130 levels versus Sham + VEH and Sham + sgp130-Fc mice. There was no treatment effect on IL-6, sIL6-R or sgp130 in Sham + VEH versus Sham + sgp130-Fc mice. There was also no treatment effect on IL-6 in CCI + VEH versus CCI + sgp130-Fc mice. However, CCI + sgp130-Fc mice had increased sIL-6R and sgp130 versus CCI + VEH mice, demonstrating sgp130-Fc treatment effects on brain biomarkers. Inflammatory chemokines (MIP-1ß, IP-10, MIG) were increased in CCI + VEH mice versus Sham + VEH and Sham + sgp130-Fc mice. However, CCI + sgp130-Fc mice had decreased chemokine levels versus CCI + VEH mice. IL-6 positively correlated, while sgp130 negatively correlated, with chemokine levels. Overall, we found that systemic sgp130-Fc treatment after CCI improved learning, decreased anxiety and reduced CCI-induced brain chemokines. Future studies will explore sex-specific dosing and treatment mechanisms for sgp130-Fc therapy.


Assuntos
Lesões Encefálicas Traumáticas , Receptor gp130 de Citocina , Modelos Animais de Doenças , Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Camundongos , Masculino , Receptor gp130 de Citocina/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Quimiocinas/metabolismo , Interleucina-6/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia
10.
Brain Behav Immun ; 119: 908-918, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761818

RESUMO

BACKGROUND: Accumulating evidence indicates that higher prenatal maternal inflammation is associated with increased depression risk in adolescent and adult-aged offspring. Prenatal maternal inflammation (PNMI) may increase the likelihood for offspring to have lower cognitive performance, which, in turn, may heighten risk for depression onset. Therefore, this study explored the potential mediating role of childhood cognitive performance in the relationship between PNMI and adolescent depressive symptoms in offspring. METHODS: Participants included 696 mother-offspring dyads from the Child Health and Development Studies (CHDS) cohort. Biomarkers of maternal inflammation [interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptor-II (sTNF-RII)] were assayed from first (T1) and second trimester (T2) sera. Childhood (ages 9-11) cognitive performance was assessed via standardized Peabody Picture Vocabulary Test (PPVT), a measure of receptive vocabulary correlated with general intelligence. Adolescent (ages 15-17) depressive symptoms were assessed via self-report. RESULTS: There were no significant associations between T1 biomarkers and childhood PPVT or adolescent depressive symptoms. Higher T2 IL1-RA was directly associated with lower childhood PPVT (b = -0.21, SE = 0.08, t = -2.55, p = 0.01), but not with adolescent depressive symptoms. T2 IL-6 was not directly associated with childhood PPVT, but higher T2 IL-6 was directly associated at borderline significance with greater depressive symptoms in adolescence (b = 0.05, SE = 0.03, t = 1.96, p = 0.05). Lower childhood PPVT predicted significantly higher adolescent depressive symptoms (b = -0.07, SE = 0.02, t = -2.99, p < 0.01). There was a significant indirect effect of T2 IL-1RA on adolescent depressive symptoms via childhood PPVT (b = 0.03, 95 % CI = 0.002-0.03) indicating a partially mediated effect. No significant associations were found with T2 sTNF-RII nor IL-8. CONCLUSIONS: Lower childhood cognitive performance, such as that indicated by a lower PPVT score, represents a potential mechanism through which prenatal maternal inflammation contributes to adolescent depression risk in offspring.


Assuntos
Biomarcadores , Cognição , Depressão , Inflamação , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Adolescente , Criança , Cognição/fisiologia , Masculino , Efeitos Tardios da Exposição Pré-Natal/imunologia , Biomarcadores/sangue , Interleucina-6/sangue , Adulto , Proteína Antagonista do Receptor de Interleucina 1/sangue
11.
J Alzheimers Dis ; 99(4): 1361-1374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38788079

RESUMO

Background: The aging population and high rates of Alzheimer's disease (AD) create significant medical burdens, prompting a need for early prevention. Targeting modifiable risk factors like vascular risk factors (VRFs), closely linked to AD, may provide a promising strategy for intervention. Objective: This study investigates how VRFs influence cognitive performance and brain structures in a community-based cohort. Methods: In this cross-sectional study, 4,667 participants over 50 years old, drawn from the Beijing Ageing Brain Rejuvenation Initiative project, were meticulously examined. Cognitive function and VRFs (diabetes mellitus, hypertension, hyperlipidemia, obesity, and smoking), were comprehensively assessed through one-to-one interviews. Additionally, a subset of participants (n = 719) underwent MRI, encompassing T1-weighted and diffusion-weighted scans, to elucidate gray matter volume and white matter structural network organization. Results: The findings unveil diabetes as a potent detriment to memory, manifesting in atrophy within the right supramarginal gyrus and diminished nodal efficiency and degree centrality in the right inferior parietal lobe. Hypertension solely impaired memory without significant structural changes. Intriguingly, individuals with comorbid diabetes and hypertension exhibited the most pronounced deficits in both brain structure and cognitive performance. Remarkably, hyperlipidemia emerged as a factor associated with enhanced cognition, and preservation of brain structure. Conclusions: This study illuminates the intricate associations between VRFs and the varied patterns of cognitive and brain structural damage. Notably, the synergistic effect of diabetes and hypertension emerges as particularly deleterious. These findings underscore the imperative to tailor interventions for patients with distinct VRF comorbidities, especially when addressing cognitive decline and structural brain changes.


Assuntos
Envelhecimento , Encéfalo , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Envelhecimento/patologia , Envelhecimento/fisiologia , Estudos Transversais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Coortes , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Cognição/fisiologia
12.
Seizure ; 119: 36-43, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776616

RESUMO

PURPOSE: Subjective and objective cognition often show weak overlap in persons with epilepsy (PWE). Over- as well as underestimation may occur. In particular after epilepsy surgery, objective memory decline is often not subjectively reported. Additionally, studies on how concordance of subjective and objective cognition changes over time are missing. Therefore, we study the extent of concordance in operated and non-operated PWE over time. METHODS: Candidates for resective epilepsy surgery were assessed between 03/18 and 12/20 (T1) with self-report questionnaires and underwent a neuropsychological examination. For 21 operated as well as 27 non-operated PWE follow-up data was obtained one to three years later (T2). Concordance of attention and memory were compared between groups and time points. Moreover, reliable change was calculated and compared between groups. RESULTS: Of the total sample, 42 % rated their attention performance realistically and 25 % showed memory concordance. Differences in patterns of over- and underestimation between groups and over time occurred for attention, but not for memory. Overestimation of memory was more frequent in operated than non-operated PWE, especially at T2 (67% vs. 11 %). In the operated group, we mainly observed reliable improvement in subjective cognition and decline in objective memory, whereas non-operated PWE showed more frequently decline of simple attention. Reliable subjective and objective change did not co-occur. CONCLUSION: Concordance of subjective and objective cognition is low. Over- as well as underestimation may persist over time. Domain-specific perspectives are necessary. Tendencies of operated PWE to develop overestimation of memory after surgery should be considered in neuropsychological interventions.


Assuntos
Atenção , Cognição , Epilepsia , Testes Neuropsicológicos , Humanos , Feminino , Masculino , Adulto , Epilepsia/cirurgia , Epilepsia/psicologia , Cognição/fisiologia , Adulto Jovem , Atenção/fisiologia , Memória/fisiologia , Pessoa de Meia-Idade , Autorrelato , Adolescente
13.
J Biomed Sci ; 31(1): 46, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725007

RESUMO

BACKGROUND: Cathepsin S (CTSS) is a cysteine protease that played diverse roles in immunity, tumor metastasis, aging and other pathological alterations. At the cellular level, increased CTSS levels have been associated with the secretion of pro-inflammatory cytokines and disrupted the homeostasis of Ca2+ flux. Once CTSS was suppressed, elevated levels of anti-inflammatory cytokines and changes of Ca2+ influx were observed. These findings have inspired us to explore the potential role of CTSS on cognitive functions. METHODS: We conducted classic Y-maze and Barnes Maze tests to assess the spatial and working memory of Ctss-/- mice, Ctss+/+ mice and Ctss+/+ mice injected with the CTSS inhibitor (RJW-58). Ex vivo analyses including long-term potentiation (LTP), Golgi staining, immunofluorescence staining of sectioned whole brain tissues obtained from experimental animals were conducted. Furthermore, molecular studies were carried out using cultured HT-22 cell line and primary cortical neurons that treated with RJW-58 to comprehensively assess the gene and protein expressions. RESULTS: Our findings reported that targeting cathepsin S (CTSS) yields improvements in cognitive function, enhancing both working and spatial memory in behavior models. Ex vivo studies showed elevated levels of long-term potentiation levels and increased synaptic complexity. Microarray analysis demonstrated that brain-derived neurotrophic factor (BDNF) was upregulated when CTSS was knocked down by using siRNA. Moreover, the pharmacological blockade of the CTSS enzymatic activity promoted BDNF expression in a dose- and time-dependent manner. Notably, the inhibition of CTSS was associated with increased neurogenesis in the murine dentate gyrus. These results suggested a promising role of CTSS modulation in cognitive enhancement and neurogenesis. CONCLUSION: Our findings suggest a critical role of CTSS in the regulation of cognitive function by modulating the Ca2+ influx, leading to enhanced activation of the BDNF/TrkB axis. Our study may provide a novel strategy for improving cognitive function by targeting CTSS.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Catepsinas , Cognição , Animais , Masculino , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Catepsinas/efeitos dos fármacos , Catepsinas/genética , Catepsinas/metabolismo , Cognição/efeitos dos fármacos , Cognição/fisiologia , Camundongos Knockout , Receptor trkB/metabolismo , Receptor trkB/genética , Transativadores/genética , Transativadores/metabolismo
14.
CNS Neurosci Ther ; 30(5): e14719, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38783536

RESUMO

BACKGROUND: Methamphetamine (METH) is a psychostimulant substance with highly addictive and neurotoxic effects, but no ideal treatment option exists to improve METH-induced neurocognitive deficits. Recently, mesenchymal stem cells (MSCs)-derived exosomes have raised many hopes for treating neurodegenerative sequela of brain disorders. This study aimed to determine the therapeutic potential of MSCs-derived exosomes on cognitive function and neurogenesis of METH-addicted rodents. METHODS: Male BALB/c mice were subjected to chronic METH addiction, followed by intravenous administration of bone marrow MSCs-derived exosomes. Then, the spatial memory and recognition memory of animals were assessed by the Barnes maze and the novel object recognition test (NORT). The neurogenesis-related factors, including NeuN and DCX, and the expression of Iba-1, a microglial activation marker, were assessed in the hippocampus by immunofluorescence staining. Also, the expression of inflammatory cytokines, including TNF-α and NF-κB, were evaluated by western blotting. RESULTS: The results showed that BMSCs-exosomes improved the time spent in the target quadrant and correct-to-wrong relative time in the Barnes maze. Also, NORT's discrimination index (DI) and recognition index (RI) were improved following exosome therapy. Additionally, exosome therapy significantly increased the expression of NeuN and DCX in the hippocampus while decreasing the expression of inflammatory cytokines, including TNF-α and NF-κB. Besides, BMSC-exosomes down-regulated the expression of Iba-1. CONCLUSION: Our findings indicate that BMSC-exosomes mitigated METH-caused cognitive dysfunction by improving neurogenesis and inhibiting neuroinflammation in the hippocampus.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Proteína Duplacortina , Exossomos , Hipocampo , Células-Tronco Mesenquimais , Metanfetamina , Camundongos Endogâmicos BALB C , Neurogênese , Animais , Exossomos/metabolismo , Masculino , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Camundongos , Metanfetamina/toxicidade , Transtornos Relacionados ao Uso de Anfetaminas/terapia , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Cognição/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Estimulantes do Sistema Nervoso Central/toxicidade , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Proteínas dos Microfilamentos/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA
15.
BMC Geriatr ; 24(1): 426, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741042

RESUMO

OBJECTIVE: To examine the bi-directorial association between diversified leisure activity participation and cognitive function over a 7-year period. METHODS: Data analyzed was from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a large-scale longitudinal national study. The baseline survey was conducted in 2011 with follow-up every three years. We traced a total of 2718 participants over a period of 7 years. We used adjusted random intercept cross-lagged panel models (RI-CLPMs) to examine the bi-directorial associations between diversified leisure activity participation and cognitive function. RESULTS: We observed bi-directorial associations between diversity of leisure activity and cognitive function across waves at the between-person and within-person levels. The adjusted random intercept cross-lagged panel models fitted the data appropriately, and the 3-year cross-lagged effects of prior diversified leisure activity participation on cognitive function (ß = 0.058, p < 0.01) and cognitive function on subsequent diversified leisure activity participation (ß = 0.047, p < 0.05) were significant. The results remained after adjusting the model for baseline sex, age, educational level, marital status and current residence, the number of chronic diseases, ADL, depressive symptoms, sleep quality, smoking, and drinking. CONCLUSION: This study suggests that a reciprocal causality relationship between diversified leisure activity participation and cognitive function, indicating a "positive circle" that further promotes cognition over time.


Assuntos
Cognição , Atividades de Lazer , Humanos , Atividades de Lazer/psicologia , Masculino , Feminino , China/epidemiologia , Idoso , Cognição/fisiologia , Estudos Longitudinais , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
16.
Acta Neurochir (Wien) ; 166(1): 204, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713405

RESUMO

PURPOSE: Mapping higher-order cognitive functions during awake brain surgery is important for cognitive preservation which is related to postoperative quality of life. A systematic review from 2018 about neuropsychological tests used during awake craniotomy made clear that until 2017 language was most often monitored and that the other cognitive domains were underexposed (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). The field of awake craniotomy and cognitive monitoring is however developing rapidly. The aim of the current review is therefore, to investigate whether there is a change in the field towards incorporation of new tests and more complete mapping of (higher-order) cognitive functions. METHODS: We replicated the systematic search of the study from 2018 in PubMed and Embase from February 2017 to November 2023, yielding 5130 potentially relevant articles. We used the artificial machine learning tool ASReview for screening and included 272 papers that gave a detailed description of the neuropsychological tests used during awake craniotomy. RESULTS: Comparable to the previous study of 2018, the majority of studies (90.4%) reported tests for assessing language functions (Ruis, J Clin Exp Neuropsychol 40(10):1081-1104, 218). Nevertheless, an increasing number of studies now also describe tests for monitoring visuospatial functions, social cognition, and executive functions. CONCLUSIONS: Language remains the most extensively tested cognitive domain. However, a broader range of tests are now implemented during awake craniotomy and there are (new developed) tests which received more attention. The rapid development in the field is reflected in the included studies in this review. Nevertheless, for some cognitive domains (e.g., executive functions and memory), there is still a need for developing tests that can be used during awake surgery.


Assuntos
Cognição , Craniotomia , Testes Neuropsicológicos , Vigília , Humanos , Craniotomia/métodos , Craniotomia/efeitos adversos , Vigília/fisiologia , Cognição/fisiologia , Monitorização Intraoperatória/métodos , Monitorização Neurofisiológica Intraoperatória/métodos
18.
BMC Geriatr ; 24(1): 460, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797829

RESUMO

BACKGROUND: The aging global population is experiencing escalating challenges related to cognitive deficits and dementia. This study explored the interplay between pulmonary function, physical activity, and cognitive function in older U.S. adults to identify modifiable risk factors for cognitive decline. METHODS: Utilizing NHANES 2011-2012 data, we conducted a cross-sectional analysis of 729 participants aged ≥ 60 years. Cognitive function, peak expiratory flow (PEF), and physical activity were assessed. Weighted logistic regression and mediation analyses were employed to examine associations. RESULTS: The sample size was 729 (weighted mean [SD] age, 67.1 [5.3] years; 53.6% female participants). Preliminary correlation analysis indicated a positive correlation between the global cognitive score and physical activity (ß = 0.16; p < 0.001), recreational activity (ß = 0.22; p < 0.001), and PEF in percent predicted (PEF%) (ß = 0.18; p < 0.001). Compared to those with a PEF% >100%, the PEF% (80-100%) group (OR, 2.66; 95% CI, 1.34-5.29; p = 0.005) and PEF% <80% group (OR, 3.36; 95% CI, 1.67-6.76; p = 0.001) were significantly associated with higher cognitive deficits risk. Recreational activity meeting guidelines was linked to a lower risk of cognitive deficits (OR, 0.24; 95% CI, 0.10-0.57; p = 0.001). Mediation analysis demonstrated that PEF mediates the relationship between physical activity and cognitive function. CONCLUSION: This study revealed significant associations between lower PEF, diminished physical activity, and increased cognitive deficits in elderly individuals. The results supported the hypothesis that pulmonary function may mediate the connection between activity and cognitive health, emphasizing the importance of respiratory health in cognitive aging. Recognizing these associations is crucial for clinical care and public health policy aiming to mitigate cognitive decline in aging populations. While these findings are intriguing, validation through longitudinal design studies is deemed necessary.


Assuntos
Envelhecimento , Cognição , Exercício Físico , Humanos , Feminino , Estudos Transversais , Masculino , Idoso , Pico do Fluxo Expiratório/fisiologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Cognição/fisiologia , Envelhecimento/fisiologia , Envelhecimento/psicologia , Pessoa de Meia-Idade , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Inquéritos Nutricionais/métodos
19.
Acta Neurochir (Wien) ; 166(1): 226, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777952

RESUMO

BACKGROUND AND PURPOSE: In recent years there has been a re-evaluation regarding the clinical implications of temporal lobe arachnoid cysts (temporal arachnoid cysts) in children. These cysts have often been considered asymptomatic, or if symptomatic, only causing focal neurological symptoms or signs of increased intracranial pressure. However, several studies have more recently reported on cognitive symptoms improving after surgery. This study aimed to evaluate if reported cognitive improvement after surgery of temporal arachnoid cysts were stable after five years. METHOD: Ten consecutive children (m = 14.65; range 12.1-19.415 were assessed cognitively five years after micro-neurosurgical fenestration of a temporal arachnoid cyst. Results were compared to results from their pre- and post-surgical evaluations. Evaluations included the Wechsler-scales, Boston Naming Test (BNT), Rey Auditory Verbal Learning Test (RAVLT), verbal fluency test (FAS) and Rey Complex Figure Test (RCFT). RESULTS: The analysis revealed significant postsurgical improvement compared to baseline on the Wechsler-scales measures of general intelligence (FSIQ), verbal abilities (VCI) and processing speed (PSI). Mean differences after surgery were 8.3 for FSIQ, (p = 0.026), 8.5 for VI (p = < .01) and 9.9 for PSI (p = 0.03). There were no significant differences in mean test results when comparing postsurgical scores with scores five years after surgery, indicating long-term stability of improvements. CONCLUSION: The results indicate that affected cognitive functions in children with temporal arachnoid cysts improve after surgery and that the improvements remain stable five years later. The improvements and long term stability were also consistent with the experience of both parents and children. The findings provide a strong argument for neurosurgical fenestration of temporal arachnoid cysts in children.


Assuntos
Cistos Aracnóideos , Cognição , Humanos , Cistos Aracnóideos/cirurgia , Masculino , Feminino , Criança , Seguimentos , Adolescente , Cognição/fisiologia , Adulto Jovem , Procedimentos Neurocirúrgicos/métodos , Microcirurgia/métodos , Testes Neuropsicológicos/estatística & dados numéricos , Resultado do Tratamento , Lobo Temporal/cirurgia
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