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Background: There are indications for sex-specific differences regarding the association between kallikrein-8 (KLK8) and cognitive impairment in early stages of Alzheimer's disease for which KLK8 may be an early blood-based biomarker. These may be due to different levels of sex hormones. To correctly interpret KLK8 blood concentrations, sex-specific analyses are needed. Objective: The aim of our exploratory study was to investigate sex-specific differences in blood-based KLK8 in participants of the population-based Heinz Nixdorf Recall study with different cognitive status and the association between KLK8 and sex hormones. Methods: In 290 participants (45% women, 69.7±7.4 years (mean±SD)) we investigated sex-specific serum KLK8 differences between cognitively unimpaired (CU, 43%) and cognitively impaired (CI) participants and the association between KLK8 and dehydroepiandrosteronsulfate (DHEAS), estradiol and testosterone, using adjusted multiple linear regression. Results: The mean±SD KLK8 was similar for CU men (808.1±729.6âpg/ml) and women (795.9±577.7âpg/ml); adjusted mean-difference [95%-CI]: -95.3 [-324.1;133.5] pg/ml. KLK8 was lower in CI women (783.5±498.7âpg/ml) than men (1048.4±829âpg/ml); -261 [-493.1; -29] pg/ml. In men but not women, there was a weak indication for a positive slope between estradiol (11.9 [-0.4;24.3] pg/ml) and DHEAS (1.4 [-0.5;3.3] pg/ml) with KLK8, while testosterone had no impact. Conclusions: The results suggested a different role for KLK8 in the development of cognitive impairment in men and women, potentially influenced by sex hormones. To use blood KLK8 as an early biomarker, further research on hormonal regulation of KLK8 expression is needed as a part of the investigation of the KLK8 involvement in cognitive impairment and Alzheimer's disease pathology.
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Biomarcadores , Disfunción Cognitiva , Calicreínas , Humanos , Femenino , Masculino , Calicreínas/sangre , Anciano , Disfunción Cognitiva/sangre , Biomarcadores/sangre , Persona de Mediana Edad , Testosterona/sangre , Estradiol/sangre , Caracteres Sexuales , Sulfato de Deshidroepiandrosterona/sangre , Enfermedad de Alzheimer/sangre , Factores SexualesRESUMEN
Due to worldwide demographic change, the number of older persons in the population is increasing. Aging is accompanied by changes of sleep structure, deposition of beta-amyloid (Aß) and tau proteins and vascular changes and can turn into mild cognitive impairment (MCI) as well as dementia. Sleep disorders are discussed both as a risk factor for and as a consequence of MCI/dementia. Cross-sectional and longitudinal population-based as well as case-control studies revealed sleep disorders, especially sleep-disorderded breathing (SDB) and excessive or insufficient sleep durations, as risk factors for all-cause MCI/dementia. Regarding different dementia types, SDB was especially associated with vascular dementia while insomnia/insufficient sleep was related to an increased risk of Alzheimer's disease (AD). Scarce and still inconsistent evidence suggests that therapy of sleep disorders, especially continuous positive airway pressure (CPAP) in SDB, can improve cognition in patients with sleep disorders with and without comorbid dementia and delay onset of MCI/dementia in patients with sleep disorders without previous cognitive impairment. Regarding potential pathomechanisms via which sleep disorders lead to MCI/dementia, disturbed sleep, chronic sleep deficit and SDB can impair glymphatic clearance of beta-amyloid (Aß) and tau which lead to amyloid deposition and tau aggregation resulting in changes of brain structures responsible for cognition. Orexins are discussed to modulate sleep and Aß pathology. Their diurnal fluctuation is suppressed by sleep fragmentation and the expression suppressed at the point of hippocampal atrophy, contributing to the progression of dementia. Additionally, sleep disorders can lead to an increased vascular risk profile and vascular changes such as inflammation, endothelial dysfunction and atherosclerosis which can foster neurodegenerative pathology. There is ample evidence indicating that changes of sleep structure in aging persons can lead to dementia and also evidence that therapy of sleep disorder can improve cognition. Therefore, sleep disorders should be identified and treated early.
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Little is known about the impact of long-term ambient air pollution (AP) and noise exposure on change in cognitive function over years in the elderly. In this study, we wanted to examine the association between long-term exposure to AP and noise with the rate of cognitive decline in a population aged 50 and older and susceptible groups with mild cognitive impairment or at a genetically higher risk of Alzheimer's disease (Apolipoprotein E ε4 positive). Participants in the German population-based Heinz Nixdorf Recall study carried out five neuropsychological tests. Individual tests scores at the first (T1 = 2006-2008) and second (T2 = 2011-2015) follow-up for each test were used as outcomes after standardization using predicted means adjusted for age and education. Global cognitive score (GCS) was defined as sum of five standardized scores of individual tests. Long-term exposures to particulate matter (PM2.5, PM10, PM2.5 absorbance), accumulation mode particle number (PNacc), a proxy of ultrafine particles, and nitrogen dioxide were estimated by the land-use regression and chemistry transport models. Noise exposures were assessed as outdoor weighted nighttime road traffic noise (Lnight) means. We performed linear regression analyses adjusted for sex, age, individual and neighborhood socio-economic status, and lifestyle variables. Effect modification in vulnerable groups was estimated using multiplicative interaction terms between exposure and a modifier. Overall, 2554 participants (49.5% men, median age is 63 (IQR = 12)) were included. We found weak associations between higher exposure to PM10 and PM2.5 with faster decline in the immediate verbal memory test. Adjustment for potential confounders and for co-exposures did not change the results. We saw no effects on GCS, and no effect of noise exposure. In susceptible groups, higher AP and noise exposure were tended to be associated with faster decline in GCS. Our results suggest that AP exposure may accelerate cognitive decline in older ages, particularly in susceptible groups.
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Contaminantes Atmosféricos , Contaminación del Aire , Disfunción Cognitiva , Masculino , Anciano , Humanos , Persona de Mediana Edad , Femenino , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/efectos adversos , Contaminación del Aire/efectos adversos , Material Particulado/efectos adversos , Material Particulado/análisis , Disfunción Cognitiva/epidemiologíaRESUMEN
Background: Blood kallikrein-8 is supposed to be a biomarker for mild cognitive impairment (MCI) due to Alzheimer's disease (AD), a precursor of AD dementia. Little is known about the association of kallikrein-8 and non-AD type dementias. Objective: To investigate whether blood kallikrein-8 is elevated in individuals with non-amnestic MCI (naMCI), which has a higher probability to progress to a non-AD type dementia, compared with cognitively unimpaired (CU) controls. Methods: We measured blood kallikrein-8 at ten-year follow-up (T2) in 75 cases and 75 controls matched for age and sex who were participants of the population-based Heinz Nixdorf Recall study (baseline: 2000-2003). Cognitive performance was assessed in a standardized manner at five (T1) and ten-year follow-up. Cases were CU or had subjective cognitive decline (SCD) at T1 and had naMCI at T2. Controls were CU at both follow-ups. The association between kallikrein-8 (per 500 pg/ml increase) and naMCI was estimated using conditional logistic regression: odds ratios (OR) and 95% confidence intervals (95% CI) were determined, adjusted for inter-assay variability and freezing duration. Results: Valid kallikrein-8 values were measured in 121 participants (45% cases, 54.5% women, 70.5±7.1 years). In cases, the mean kallikrein-8 was higher than in controls (922±797 pg/ml versus 884±782 pg/ml). Kallikrein-8 was not associated with having naMCI compared to being CU (adjusted; OR: 1.03 [95% CI: 0.80-1.32]). Conclusion: This is the first population-based study that shows that blood kallikrein-8 tends not to be elevated in individuals with naMCI compared with CU. This adds to the evidence of the possible AD specificity of kallikrein-8.
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BACKGROUND: White matter hyperintensities of presumed vascular origin (WMH) are frequent in cerebral magnetic resonance imaging of older people. They are promoted by vascular risk factors, especially hypertension, and are associated with cognitive deficits at the group level. It has been suggested that not only the severity, but also the location, of lesions might critically influence cognitive deficits and represent different pathologies. METHODS: In 560 participants (65.2 ± 7.5 years, 51.4% males) of the population-based 1000BRAINS study, we analyzed the association of regional WMH using Fazekas scoring separately for cerebral lobes, with hypertension and cognition. RESULTS: WMH most often affected the frontal lobe (83.7% score >0), followed by the parietal (75.8%), temporal (32.7%), and occipital lobe (7.3%). Higher Fazekas scores in the frontal, parietal, and temporal lobe were associated with higher blood pressure and antihypertensive treatment in unadjusted ordinal regression models and in models adjusted for age, sex, and vascular risk factors (e.g., age- and sex-adjusted odds ratio = 1.14, 95% confidence interval = 1.03-1.25 for the association of frontal lobe WMH Fazekas score with systolic blood pressure [SBP] [per 10 mm Hg]; 1.13 [1.02-1.23] for the association of parietal lobe score with SBP; 1.72 [1.19-2.48] for the association of temporal lobe score with antihypertensive medications). In linear regressions, higher frontal lobe scores were associated with lower performance in executive function and non-verbal memory, and higher parietal lobe scores were associated with lower performance in executive function, verbal-, and non-verbal memory. CONCLUSIONS: Hypertension promotes WMH in the frontal, parietal, and temporal lobe. WMH in the frontal and parietal lobe are associated with reduced executive function and memory.
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Trastornos del Conocimiento , Hipertensión , Sustancia Blanca , Masculino , Humanos , Anciano , Femenino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Antihipertensivos , Cognición/fisiología , Trastornos del Conocimiento/patología , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Background: Depression might be an independent risk factor for cognitive decline, a prodromal dementia symptom or a reaction to cognitive/functional impairment. Objective: To investigate the association between (1) depressive symptoms and (2) depressive symptom patterns over 13 years with incident mild cognitive impairment (MCI) 5 years later. Materials and methods: We included 724/823 cognitively unimpaired men/women who participated in the population-based Heinz Nixdorf Recall study (t1: 2005-2008, ø62.9 years; t2: 2010-2015, ø68.1 years). Depressive symptoms were assessed in the study center and during six postal follow-ups using the short form of the Center for Epidemiologic Studies Depression Scale (CES-D). Relative risks (RR; 95% confidence intervals) for MCI at t2 (men/women: 71/76) were estimated for CES-D at t1 (linear and dichotomized at ≥17, cut-off for clinically relevant depressive symptoms) and CES-D fluctuations over 13 years (stable low, large fluctuations, stable high/stable around cut-off) using log-linear regression models with Poisson working likelihood adjusted for age, sex, education, diabetes mellitus, coronary heart disease, and stroke. Results: Fully adjusted risk for MCI at t2 (per CES-D point increase at t1) was elevated for the total cohort (1.053, 1.031-1.076), men (1.046, 1.012-1.081), and women (1.059, 1.029-1.090). Applying the dichotomized CES-D, risk for MCI was substantially increased for the total cohort [2.22 (1.38-3.58)] and in women [2.59 (1.46-4.58)]. Large CES-D fluctuations and stable high/stable around cut-off were associated with increased RR for MCI in the total cohort and in women compared to stable low symptoms. Conclusion: Depressive symptoms predicted MCI in cognitively unimpaired participants of our population-based study. Adequate treatment of depression may therefore contribute to the maintenance of normal cognition and delay dementia onset.
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INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs. Reports of persistent or newly emergent symptoms, including those related to the nervous system, have increased over the course of the pandemic, leading to the introduction of post-COVID-19 syndrome. However, this novel syndrome is still ill-defined and structured objectification of complaints is scarce. Therefore, we performed a prospective observational cohort study to better define and validate subjective neurological disturbances in patients with post-COVID-19 syndrome. METHODS: A total of 171 patients fulfilling the post-COVID-19 WHO Delphi consensus criteria underwent a comprehensive neurological diagnostic work-up including neurovascular, electrophysiological, and blood analysis. In addition, magnetic resonance imaging (MRI) and lumbar puncture were conducted in subgroups of patients. Furthermore, patients underwent neuropsychological, psychosomatic, and fatigue assessment. RESULTS: Patients were predominantly female, middle-aged, and had incurred mostly mild-to-moderate acute COVID-19. The most frequent post-COVID-19 complaints included fatigue, difficulties in concentration, and memory deficits. In most patients (85.8%), in-depth neurological assessment yielded no pathological findings. In 97.7% of the cases, either no diagnosis other than post COVID-19 syndrome, or no diagnosis likely related to preceding acute COVID-19 could be established. Sensory or motor complaints were more often associated with a neurological diagnosis other than post-COVID-19 syndrome. Previous psychiatric conditions were identified as a risk factor for developing post-COVID-19 syndrome. We found high somatization scores in our patient group that correlated with cognitive deficits and the extent of fatigue. CONCLUSIONS: Albeit frequently reported by patients, objectifiable affection of the nervous system is rare in post-COVID-19 syndrome. Instead, elevated levels of somatization point towards a pathogenesis potentially involving psychosomatic factors. However, thorough neurological assessment is important in this patient group in order to not miss neurological diseases other than post-COVID-19.
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OBJECTIVES: White matter hyperintensities (WMH) of presumed vascular origin are frequent in cerebral MRI of older people. They represent a sign of small vessel disease, are promoted by arterial hypertension, and relate to cognitive deficits. The interdependence of blood pressure and its treatment, WMH, and cognitive performance has not systematically been studied in population-based studies. METHODS: Consequently, we analysed the interdependence of SBP, DBP, and antihypertensive medications, as well as BP/treatment category, with WMH and cognitive performance in 560 participants of the population-based 1000BRAINS study. RESULTS: BP, its treatment, and BP/treatment category were moderately associated with cognitive performance (e.g. unadjusted ß â=â-0.10, 95%CIâ=â-0.19 to -0.02 for the association of SBP (per standard deviation of 17.2âmmHg) with global cognition (per standard deviation of 0.5 z score)]. The harmful effect of BP on cognition was strongly mediated by periventricular hyperintensities (PVH), which were significantly associated with both SBP [ ß â=â0.24, 95% CIâ=â0.14-0.34 (per 1-point-increase in Fazekas score)] and global cognition ( ß â=â-0.22, 95%CIâ=â -0.32 to -0.13). Thus, PVH mediated as much as 52% of the effects of SBP on cognitive performance. Mediation was less strong for deep white matter hyperintensities (DWMH, 16%), which showed less association with SBP ( ß â=â0.14, 95% CIâ=â0.05-0.24) and global cognition ( ß â=â-0.12, 95%CIâ=â-0.21 to -0.03). Regarding different cognitive domains, PVH most strongly mediated effects of SBP on nonverbal memory (94%) and executive function (81%). CONCLUSION: Our results indicate that PVH may predispose to cognitive impairment associated with hypertension, especially in the domains of nonverbal memory and executive function.
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Disfunción Cognitiva , Hipertensión , Sustancia Blanca , Humanos , Anciano , Hipertensión/complicaciones , Imagen por Resonancia Magnética/métodos , Disfunción Cognitiva/complicaciones , Cognición/fisiologíaRESUMEN
OBJECTIVE: We provide normative data for the Trail Making Test (TMT)-A and B and the derived scores B - A and B/A, for the German general population aged 57-84 years. METHODS: Data were derived from the third examination of the population-based Heinz Nixdorf Recall study. We excluded participants with a history of dementia or stroke, a depression score above cutoff (CES-D Center for Epidemiologic Studies Depression Scale score ≥ 18), or mild cognitive impairment according to a neurocognitive test battery. The normative sample (n = 2,182) was stratified by age, using the interval superposition approach, and by three levels of educational attainment (up to 10 years of schooling; >10 years of schooling; and university degree). RESULTS: We tabulated test performance scores at percentage rank thresholds 5, 10, 15, 20, 25, 50, 75, and 90. In multiple linear regression, TMT-A performance declined by 1 s each year of life, and TMT-B performance by 3 s; educational level had an impact of up to 30 s in TMT-B. TMT-B/A was only weakly associated with age and education. TMT-B and B - A correlated r = 0.96. Completion of the TMT-B within the time limit of 300 s was not achieved by 10.9% of participants >74 years, and especially by those >74 years who were on the lowest educational level (13.9%). CONCLUSIONS: For TMT-A, TMT-B, and B - A, the narrow age categorization and distinction between three educational levels proved meaningful. The 300 s limit for the TMT-B impedes the identification of thresholds for very low performance in this age group and needs reconsideration.
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Disfunción Cognitiva , Humanos , Pruebas de Estado Mental y Demencia , Pruebas Neuropsicológicas , Valores de Referencia , Prueba de Secuencia AlfanuméricaRESUMEN
BACKGROUND: Kallikrein-8 (KLK8) might be an early blood-biomarker of Alzheimer's disease (AD). We examined whether blood KLK8 is elevated in persons with amnestic mild cognitive impairment (aMCI) which is a precursor of AD, compared to cognitively unimpaired (CU) controls. METHODS: Forty cases and 80 controls, matched by sex and age (± 3years), were participants of the longitudinal population-based Heinz Nixdorf Recall study (baseline: 2000-2003). Standardized cognitive performance was assessed 5 (T1) and 10 years after baseline (T2). Cases were CU at T1 and had incidental aMCI at T2. Controls were CU at T1 and T2. Blood KLK8 was measured at T2. Using multiple logistic regression the association between KLK8 in cases vs. controls was investigated by estimating odds ratios (OR) and 95% confidence intervals (95%CI), adjusted for inter-assay variability and freezing duration. Using receiver operating characteristic (ROC) analysis, the diagnostic accuracy of KLK8 was determined by estimating the area under the curve (AUC) and 95%CI (adjusted for inter-assay variability, freezing duration, age, sex). RESULTS: Thirty-seven participants with aMCI vs. 72 CU (36.7%women, 71.0±8.0 (mean±SD) years) had valid KLK8 measurements. Mean KLK8 was higher in cases than in controls (911.6±619.8 pg/ml vs.783.1±633.0 pg/ml). Fully adjusted, a KLK8 increase of 500pg/ml was associated with a 2.68 (1.05-6.84) higher chance of having aMCI compared to being CU. With an AUC of 0.92 (0.86-0.97), blood KLK8 was a strong discriminator for aMCI and CU. CONCLUSION: This is the first population-based study to demonstrate the potential clinical utility of blood KLK8 as a biomarker for incipient AD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Calicreínas , Enfermedad de Alzheimer/diagnóstico , Biomarcadores , Disfunción Cognitiva/psicología , Femenino , Humanos , Calicreínas/sangre , Recuerdo Mental , Pruebas NeuropsicológicasRESUMEN
[Figure: see text].
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Presión Sanguínea/fisiología , Hipertensión/tratamiento farmacológico , Sustancia Blanca/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipertensión/patología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The apolipoprotein E (APOE) É4 allele is reported to be a strong genetic risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Additional genetic loci have been detected that influence the risk for late-onset AD. As socioeconomic position (SEP) is also strongly related to cognitive decline, SEP has been suggested to be a possible modifier of the genetic effect on MCI. OBJECTIVE: To investigate whether APOEÉ4 and a genetic sum score of AD-associated risk alleles (GRSAD) interact with SEP indicators to affect MCI in a population-based cohort. METHODS: Using data of 3,834 participants of the Heinz Nixdorf Recall Study, APOEÉ4 and GRSAD by SEP interactions were assessed using logistic regression models, as well as SEP-stratified genetic association analysis. Interaction on additive scale was calculated using the relative excess risk due to interaction (RERI). All analysis were additionally stratified by sex. RESULTS: Indication for interaction on the additive scale was found between APOEÉ4 and low education on MCI (RERI: 0.52 [95% confidence interval (CI): 0.01; 1.03]). The strongest genetic effects of the APOEÉ4 genotype on MCI were observed in groups of low education (Odds ratio (OR): 1.46 [95% CI: 0.79; 2.63] for≤10 years of education versus OR: 1.00 [95% CI: 0.43; 2.14] for≥18 years of education). Sex stratified results showed stronger effects in women. No indication for interaction between the GRSAD and SEP indicators on MCI was observed. CONCLUSION: Results indicate that low education may have an impact on APOEÉ4 expression on MCI, especially among women.
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Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Disfunción Cognitiva/genética , Factores Socioeconómicos , Alelos , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores SexualesRESUMEN
The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55-87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = - 0.042 (verbal fluency) and - 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI - 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55-65 years, 66-75 years, > 75 years). In the 66-75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.
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Cognición , Disfunción Cognitiva/genética , Glucuronidasa/genética , Haplotipos/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/patología , Femenino , Genotipo , Geriatría , Heterocigoto , Humanos , Proteínas Klotho , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
The current coronavirus disease 2019 (COVID-19) pandemic represents a severe, life-changing event for people across the world. Life changes may involve job loss, income reduction due to furlough, death of a beloved one, or social stress due to life habit changes. Many people suffer from social isolation due to lockdown or physical distancing, especially those living alone and without family. This article reviews the association of life events and social isolation with cardiovascular disease, assembling the current state of knowledge for stroke and coronary heart disease. Possible mechanisms underlying the links between life events, social isolation, and cardiovascular disease are outlined. Furthermore, groups with increased vulnerability for cardiovascular disease following life events and social isolation are identified, and clinical implications of results are presented.
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COVID-19/psicología , Enfermedad Coronaria/psicología , SARS-CoV-2/patogenicidad , Aislamiento Social/psicología , Accidente Cerebrovascular/psicología , Ansiedad/psicología , COVID-19/virología , Control de Enfermedades Transmisibles/métodos , Enfermedad Coronaria/virología , HumanosRESUMEN
BACKGROUND: Midlife hypertension is a risk factor for cognitive decline in late-life but little is known about the impact of long-term hypertension on cognitive change over time. METHODS: We examined blood pressure and cognitive function in 2777 participants (baseline: 2000-2003, 45-75 years, 48.4% men) from the Heinz Nixdorf Recall study. Blood pressure was assessed at three study visits and cognitive function was assessed at both follow-ups (mean follow-up: 5.1 years). Z-score differences in five neuropsychological tests, defining cognitive decline, were derived from linear regression models including age and education. The association of cognitive decline over 5 years and blood pressure over 10 years (classified as: normal blood pressure (>10 years, reference), prevalent hypertension (>10 years), incident hypertension t1 (>5 years), incident hypertension t2 (<5 years), temporary hypertension (at least one hypertensive reading)) was calculated using linear regression models resulting in coefficient b and 95% confidence interval. We calculated interactions with age (linear and with a cutoff at 65 years). RESULTS: Participants with prevalent hypertension showed a greater cognitive decline in both verbal memory tests. Incident hypertension t1 was associated with a greater decline in the visuospatial organization test. There was no interaction with age. CONCLUSION: This study showed that prevalent high blood pressure over 10 years is related to cognitive decline. Prevalent hypertension with longer exposure time may be more detrimental than temporary hypertension for cognitive function.
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Envejecimiento , Disfunción Cognitiva/epidemiología , Hipertensión/epidemiología , Anciano , Disfunción Cognitiva/diagnóstico , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Hipertensión/diagnóstico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de RiesgoRESUMEN
Cognitive functioning after transplantation, which could influence medication compliance and independence, has not been well studied. This study investigated cognitive impairment after lung transplantation. Patients undergoing bilateral transplant between March 2013 and October 2015 underwent comprehensive neuropsychological assessment at 60.1 ± 44.1 months post-transplantation: verbal memory (Auditory-Verbal Learning Test, digit span forward), visual memory (Corsi Block-Tapping Test forward, Benton Visual Retention Test), concentration/speed of processing/attention (D2 Test of Attention, Trail Making Test (TMT) A, Grooved Pegboard), and executive functioning (TMT B, Stroop Color-Word Test, semantic and phonematic verbal fluency, digit span backward, Corsi Block-Tapping Test backward). Mean scores were compared with a normative dataset using a one-sample t-test. A cognitive domain was judged impaired if the score on two or more domain-specific tests was greater than one standard deviation below the normative dataset age range mean. Of 124 lung transplant recipients (51% male, 54.3 ± 9.0 years), 70% showed cognitive impairment in one or more domains. Executive function was most often impaired (78% of recipients not within the age range) followed by verbal memory impairment (72% not within the age range). Cognitive function reductions were largely independent of age, gender, education, immunosuppressive medications, and time since transplantation. The findings show that cognitive impairment is common after lung transplantation and should be subject to rehabilitation and psychological resilience strategies.
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Cognición , Trasplante de Pulmón , Función Ejecutiva , Femenino , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Pruebas Neuropsicológicas , Prueba de Secuencia AlfanuméricaRESUMEN
Detection and diagnosis of early and subclinical stages of Alzheimer's Disease (AD) play an essential role in the implementation of intervention and prevention strategies. Neuroimaging techniques predominantly provide insight into anatomic structure changes associated with AD. Deep learning methods have been extensively applied towards creating and evaluating models capable of differentiating between cognitively unimpaired, patients with Mild Cognitive Impairment (MCI) and AD dementia. Several published approaches apply information fusion techniques, providing ways of combining several input sources in the medical domain, which contributes to knowledge of broader and enriched quality. The aim of this paper is to fuse sociodemographic data such as age, marital status, education and gender, and genetic data (presence of an apolipoprotein E (APOE)-ε4 allele) with Magnetic Resonance Imaging (MRI) scans. This enables enriched multi-modal features, that adequately represent the MRI scan visually and is adopted for creating and modeling classification systems capable of detecting amnestic MCI (aMCI). To fully utilize the potential of deep convolutional neural networks, two extra color layers denoting contrast intensified and blurred image adaptations are virtually augmented to each MRI scan, completing the Red-Green-Blue (RGB) color channels. Deep convolutional activation features (DeCAF) are extracted from the average pooling layer of the deep learning system Inception_v3. These features from the fused MRI scans are used as visual representation for the Long Short-Term Memory (LSTM) based Recurrent Neural Network (RNN) classification model. The proposed approach is evaluated on a sub-study containing 120 participants (aMCI = 61 and cognitively unimpaired = 59) of the Heinz Nixdorf Recall (HNR) Study with a baseline model accuracy of 76%. Further evaluation was conducted on the ADNI Phase 1 dataset with 624 participants (aMCI = 397 and cognitively unimpaired = 227) with a baseline model accuracy of 66.27%. Experimental results show that the proposed approach achieves 90% accuracy and 0.90 F1-Score at classification of aMCI vs. cognitively unimpaired participants on the HNR Study dataset, and 77% accuracy and 0.83 F1-Score on the ADNI dataset.
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Apolipoproteínas E/genética , Disfunción Cognitiva/diagnóstico , Imagen por Resonancia Magnética , Neuroimagen , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/patología , Conjuntos de Datos como Asunto , Aprendizaje Profundo , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SocioeconómicosRESUMEN
OBJECTIVES: Traffic noise is negatively associated with cognitive function, and its perception can differ between depressed and non-depressed people. We studied the role of depressive symptoms in the association between traffic noise and cognitive function. We studied the role of depressive symptoms in the association between traffic noise and cognitive function. METHODS: During the first follow-up examination (2006-2008) of the German Heinz Nixdorf Recall study, cognitive function (five subtests and an additive global summary score, GCS) and depressive symptoms (CES-D score) were assessed in 2745 participants (aged 50-80, 49.8% women). Mild cognitive impairment (MCI) was diagnosed according to the Petersen criteria in 380 participants. Long-term exposure to traffic noise was modeled as weighted 24-h mean (LDEN) and night-time mean (LNIGHT) at the façade of the baseline addresses, and was corrected for indoors (LDEN_IN and LNIGHT_IN). We developed multiple linear and logistic regression models adjusted for individual-level characteristics to investigate cross-sectionally the role of depressive symptoms in the association of traffic noise with cognitive function. RESULTS: Overall, 8.6% participants had depressive symptoms. The median noise values were LDEN 52.1 dB(A) and LDEN_IN 34.7 dB(A). Associations were slightly stronger for cognitive subtests in those with severe depression (CES-D>21), i.e., per 10 dB(A) LDEN and verbal fluency: ß = -0.04 [-0.11; 0.03] for CES-D≤21 and ß = -0.09 [-0.24; -0.06] for CES-D>21. Additional adjustment of the main model for CES-D did not change the association between noise and cognitive outcomes. Estimates using indoor noise exposure were generally stronger and more precise. CONCLUSIONS: Depressed people may be more susceptible to adverse effects of noise than non-depressed. Modeled estimates of indoor noise exposure is possibly a more appropriate measure of exposure.
Asunto(s)
Disfunción Cognitiva , Ruido del Transporte , Cognición , Disfunción Cognitiva/etiología , Depresión , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Ruido del Transporte/efectos adversosRESUMEN
Associations of sleep characteristics with mild cognitive impairment (MCI) have been examined in cross-sectional, but rarely in longitudinal studies. Incident MCI and sleep characteristics were assessed in 1,890 participants of the first and second follow-up of the Heinz Nixdorf Recall study, a population-based cohort study in Germany (age at first follow-up 50-80 years, mean follow-up 5.2 years). MCI was assessed with extensive cognitive tests. Sleep questionnaires including PSQI (Pittsburgh Sleep Quality Index) were used to assess sleep quality, sleep disturbances, time asleep, and time in bed. Relative risks (RR) of developing MCI when exposed to sleep characteristics were assessed in regression models adjusted for sociodemographic and cardiovascular risk factors. Poor sleep quality (PSQI > 5) (RR = 1.43, 95% CI: 1.12-1.82, fully adjusted, reference: PSQI ≤ 5) and difficulties initiating sleep (almost nightly versus never) (RR = 1.40, 0.94-2.08) were associated with incident MCI. For time in bed, the risk of MCI was increased for ≤ 5 hours (RR = 2.86, 1.24â6.60, reference:7 to <8 hours). In this longitudinal study with older participants, MCI risk was increased in persons with poor sleep quality, difficulties initiating sleep, and short time in bed.
Asunto(s)
Disfunción Cognitiva/fisiopatología , Autoinforme , Sueño/fisiología , Anciano , Cognición , Estudios de Cohortes , Humanos , Masculino , Riesgo , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
INTRODUCTION: Possible joint effects of subjective cognitive decline (SCD) and apolipoprotein E (APOE) ε4 genotype on incident mild cognitive impairment (MCI) were examined for men and women separately. METHODS: Cognitively normal participants with and without SCD were included from the first follow-up examination of the population-based Heinz Nixdorf Recall study. Sex-stratified logistic regression models estimated main effects and interactions (additive, multiplicative) of SCD at the first follow-up (yes+/no-) and APOE ε4 (positive+/negative-) groups for MCI 5 years later. RESULTS: Odds for MCI 5 years later were higher in SCD/APOE ε4 group +/+ than the sum of groups +/- and -/+ in women, with a trend for positive interaction. Odds for incident MCI in men was highest in group +/-, with no interaction effect. DISCUSSION: Our findings indicate that APOE ε4 may play an important role in the association of SCD and incident MCI, especially considering sex. Further studies need to examine these associations with larger sample sizes.