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1.
Hypertension ; : HYPERTENSIONAHA12016711, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33550821

RESUMO

A lower day-to-night systolic blood pressure (BP) dip has previously been associated with poor brain health and cognitive functions. Here, we sought to examine whether reduced (nighttime/daytime ratio of systolic BP >0.9 and ≤1) and reverse (nighttime/daytime ratio of systolic BP >1) dipping of systolic BP is associated with the prospective risk of being diagnosed with any dementia in Swedish older men. Twenty-four-hour ambulatory BP monitoring was used to estimate the nocturnal systolic BP dipping status of men at mean age 71 (n=997; 35% on antihypertensive medication) and 77.6 (n=611; 41% on antihypertensive medication). Dementia incidence during the observational period up to 24 years (n=286 cases) was determined by reviewing participants' medical history and independently confirmed by at least 2 experienced geriatricians. Using time-updated Cox regression (ie, time-updated information on covariates and exposure), we found that reverse systolic BP dipping was associated with a higher risk of being diagnosed with any dementia (adjusted HR, 1.64 [95% CI, 1.14-2.34], P=0.007) and Alzheimer's disease (1.67 [1.01-2.76], P=0.047) but not vascular dementia (1.29 [0.55-3.06], P=0.559). In contrast, reduced dipping of nocturnal systolic BP was not associated with a higher risk of being diagnosed with dementia. Our findings suggest that reverse systolic BP dipping may represent an independent risk factor for dementia and Alzheimer's disease in older men. Future studies should decipher whether therapies lowering nocturnal systolic BP below daytime levels, such as bedtime dosing of antihypertensive medication, can meaningfully curb the development of dementia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33153203

RESUMO

The aim of this study was to investigate whether Timed Up-and-Go (TUG) dual-task (TUGdt) tests predict dementia incidence among patients with subjective or mild cognitive impairment (SCI; MCI). Other study objectives were to determine whether TUGdt improves dementia prediction compared to a) demographic characteristics and standard cognitive tests alone; and b) TUG and Verbal Fluency performed separately. Patients (n = 172, age range 39-91 years, 78 women) with SCI or MCI performed TUGdt tests, including 1) naming animals and 2) reciting months backwards, and clinical cognitive tests at baseline. Diagnoses were identified at follow-up after 2.5 years. Logistic regression was used to predict dementia incidence, receiver operating characteristic (ROC) curves and c-statistics for predictive capacity. Analyses were stratified by age and gender. At follow-up, 51 patients had developed dementia. The TUGdt result "animals/10 s" was associated with dementia incidence (standardized odds ratio (OR) = 4.06, 95% confidence interval (CI) 2.28-7.23, p < 0.001), more so among patients under the median age of 72 years (standardized OR = 19.4, 95% CI 3.53-106.17, p < 0.001). TUGdt "animals/10 s" improved dementia prediction compared to demographic characteristics and standard tests alone (c-statistics 0.88 to 0.94) and single-task tests (c-statistics 0.86 to 0.89), but only in the younger patient group. TUGdt has the potential to become a useful tool for dementia prediction.

3.
Nutrients ; 12(9)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927800

RESUMO

Milk and fermented milk consumption has been linked to health and mortality but the association with Parkinson's disease (PD) is uncertain. We conducted a study to investigate whether milk and fermented milk intakes are associated with incident PD. This cohort study included 81,915 Swedish adults (with a mean age of 62 years) who completed a questionnaire, including questions about milk and fermented milk (soured milk and yogurt) intake, in 1997. PD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers. Multivariable-adjusted hazard ratios were obtained from Cox proportional hazards regression models. During a mean follow-up of 14.9 years, 1251 PD cases were identified in the cohort. Compared with no or low milk consumption (<40 mL/day), the hazard ratios of PD across quintiles of milk intake were 1.29 (95% CI 1.07, 1.56) for 40-159 mL/day, 1.19 (95% CI 0.99, 1.42) for 160-200 mL/day, 1.29 (95% CI 1.08, 1.53) for 201-400 mL/day, and 1.14 (95% CI 0.93, 1.40) for >400 mL/day. Fermented milk intake was not associated with PD. We found a weak association between milk intake and increased risk of PD but no dose-response relationship. Fermented milk intake was not associated with increased risk of PD.

4.
BMC Geriatr ; 20(1): 258, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727472

RESUMO

BACKGROUND: Discrimination between early-stage dementia and other cognitive impairment diagnoses is central to enable appropriate interventions. Previous studies indicate that dual-task testing may be useful in such differentiation. The objective of this study was to investigate whether dual-task test outcomes discriminate between groups of individuals with dementia disorder, mild cognitive impairment, subjective cognitive impairment, and healthy controls. METHODS: A total of 464 individuals (mean age 71 years, 47% women) were included in the study, of which 298 were patients undergoing memory assessment and 166 were cognitively healthy controls. Patients were grouped according to the diagnosis received: dementia disorder, mild cognitive impairment, or subjective cognitive impairment. Data collection included participants' demographic characteristics. The patients' cognitive test results and diagnoses were collected from their medical records. Healthy controls underwent the same cognitive tests as the patients. The mobility test Timed Up-and-Go (TUG single-task) and two dual-task tests including TUG (TUGdt) were carried out: TUGdt naming animals and TUGdt months backwards. The outcomes registered were: time scores for TUG single-task and both TUGdt tests, TUGdt costs (relative time difference between TUG single-task and TUGdt), number of different animals named, number of months recited in correct order, number of animals per 10 s, and number of months per 10 s. Logistic regression models examined associations between TUG outcomes pairwise between groups. RESULTS: The TUGdt outcomes "animals/10 s" and "months/10 s" discriminated significantly (p < 0.001) between individuals with an early-stage dementia diagnosis, mild cognitive impairment, subjective cognitive impairment, and healthy controls. The TUGdt outcome "animals/10 s" showed an odds ratio of 3.3 (95% confidence interval 2.0-5.4) for the groups dementia disorders vs. mild cognitive impairment. TUGdt cost outcomes, however, did not discriminate between any of the groups. CONCLUSIONS: The novel TUGdt outcomes "words per time unit", i.e. "animals/10 s" and "months/10 s", demonstrate high levels of discrimination between all investigated groups. Thus, the TUGdt tests in the current study could be useful as complementary tools in diagnostic assessments. Future studies will be focused on the predictive value of TUGdt outcomes concerning dementia risk for individuals with mild cognitive impairment or subjective cognitive impairment.

5.
Transl Neurodegener ; 9(1): 27, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576262

RESUMO

BACKGROUND: The clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. Here, we aimed to find protein markers in cerebrospinal fluid (CSF) from patients with FTD, presymptomatic mutation carriers and non-carriers. METHODS: Antibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD (bvFTD, n = 16) and progressive primary aphasia (PPA, n = 13), as well as presymptomatic mutation carriers (PMC, n = 16) and non-carriers (NC, n = 8). A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples. The findings were further examined in an independent cohort including 13 FTD patients, 79 patients with Alzheimer's disease and 18 healthy controls. RESULTS: We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals (PMC and NC) for 26 proteins. The analysis show patterns of separation between unaffected individuals and FTD patients, especially for those with a clinical diagnosis of bvFTD. The most statistically significant differences in protein levels were found for VGF, TN-R, NPTXR, TMEM132D, PDYN and NF-M. Patients with FTD were found to have higher levels of TN-R and NF-M, and lower levels of VGF, NPTXR, TMEM132D and PDYN, compared to unaffected individuals. The main findings were reproduced in the independent cohort. CONCLUSION: In this pilot study, we show a separation of FTD patients from unaffected individuals based on protein levels in CSF. Further investigation is required to explore the CSF profiles in larger cohorts, but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.

6.
Brain Behav ; 10(7): e01662, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32436327

RESUMO

INTRODUCTION: The purpose of our study was to compare visual rating and volumetry of brain atrophy in an elderly population over a 5-year period and compare findings with cognitive test results. MATERIALS AND METHODS: Two hundred and one subjects were examined with magnetic resonance imaging (MRI) of the brain. Visual rating and volumetry were performed in all subjects at ages 75 and 80. Cognitive function at both time points was assessed with the Mini-Mental State Examination (MMSE) and Trail Making Tests A and B (TMT-A and TMT-B). Changes in visual rating and volumetry were compared with changes in cognitive test. RESULTS: A correlation was found between visual rating of medial temporal lobe atrophy (MTA) and hippocampal volumetry at both time points (rs = -.42 and rs = -.49, p < .001, respectively). The correlation between visual rating of posterior atrophy (PA); frontal atrophy (F-GCA) and volumetry of these brain regions was significant only at age 80 (rs = -.16, p = .02 for PA and rpb = .19, p = .006 for F-GCA). Visual rating showed only a minimal progression of regional atrophy at age 80, whereas volumetry showed 2%-5% decrease in volume depending on brain region. Performance in the MMSE, TMT-A, and TMT-B was virtually unchanged between ages 75 and 80. CONCLUSION: We found a mild age-associated decrease in regional brain volumes in this healthy cohort with well-preserved cognitive functions. Visual assessment may not be sufficient for detecting mild progression of brain atrophy due to normal aging, whereas volumetry is more sensitive to capture these subtle changes.

7.
BMC Geriatr ; 19(1): 153, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142271

RESUMO

BACKGROUND: Preserved functions of daily life and cognition are cornerstones of independent aging, which is crucial for maintaining a high quality of life. The aim of this study was to examine the impact of sarcopenia, and its underlying components, on independent ageing in a cohort study of very old men. METHODS: The presence of sarcopenia and independent ageing at a mean age of 87 was investigated in 287 men from the Uppsala Longitudinal Study of Adult Men. Five years later 127 men were re-evaluated for independent ageing. Sarcopenia was defined by two different definitions from the European Working Group on Sarcopenia in Older People. In the first definition sarcopenia was defined as skeletal muscle index < 7.26 kg/m2 and either gait speed ≤0.8 m/s or hand grip strength < 30 kg. In the later up-dated definition, HGS < 27 kg and/or chair stand test > 15 s defines probable sarcopenia, which is confirmed by SMI < 7.0 kg/m2. Independent ageing was defined as a Mini-Mental State Examination score of ≥25 points, absence of diagnosed dementia, community-dwelling, independency in personal care and ability to walk outdoors alone. RESULTS: Sarcopenia at baseline was observed in 21% (60/287) and 20% (58/287), respectively, due to definition. The prevalence of independent ageing was 83% (239/288) at baseline and 69% (87/127) five years later. None of the sarcopenia diagnoses were associated with independent ageing. In contrast, gait speed was both in cross-sectional (odds ratio (OR) per one standard deviation increase 2.15, 95% confidence interval (CI) 1.47-3.15), and in longitudinal multivariate analyses (OR 1.84, 95% CI 1.19-2.82). In the cross-sectional analysis also higher hand grip strength was associated with independent ageing (OR 1.58, 95% CI 1.12-2.22), while a slower chair stand test was inversely associated (OR 0.61, 95% CI 0.43-0.86). Muscle mass; i.e. skeletal muscle index, was not associated with independent ageing. CONCLUSIONS: For very old men, especially a higher gait speed, but also a higher hand grip strength and a faster chair stand test, were associated with independent ageing, while skeletal muscle index alone, and the composite sarcopenia phenotype measured with two different definitions, were not.


Assuntos
Envelhecimento/fisiologia , Vida Independente/tendências , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Estudos de Coortes , Estudos Transversais , Seguimentos , Força da Mão/fisiologia , Humanos , Estudos Longitudinais , Masculino , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Suécia/epidemiologia , Caminhada/fisiologia
8.
J Alzheimers Dis ; 71(s1): S75-S83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31104024

RESUMO

BACKGROUND: Tools to identify individuals at preclinical stages of dementia disorders are needed to enable early interventions. Alterations in dual-task performance have been detected early in progressive neurodegenerative disorders. Hence, dual-task testing may have the potential to screen for cognitive impairment caused by neurodegeneration. Exploring correlations between dual-task performance and biomarkers of neurodegeneration is therefore of interest. OBJECTIVE: To investigate correlations between Timed Up-and-Go dual-task (TUGdt) outcomes and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-ß 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau). METHODS: This cross-sectional cohort study included 90 participants (age range 49-84 years) undergoing memory assessment, who were subsequently diagnosed with AD, other dementia disorders, mild cognitive impairment, or subjective cognitive impairment. TUG combined with "Naming Animals" (TUGdt NA) and "Months Backwards" (TUGdt MB), respectively, were used to assess dual-task performance. The number of correct words and time taken to complete the tests were measured. The CSF biomarkers were analysed by ELISA. Spearman's rank correlation was used for analyses between TUGdt outcomes (TUGdt NA and TUGdt MB), and CSF biomarkers, adjusted for age, gender, and educational level. RESULTS: The number of correct words, as well as the number of correct words/10 s during TUGdt NA correlated negatively to CSF t-tau and p-tau. No correlations were found between any time scores and CSF biomarkers. CONCLUSION: The correlations between TUGdt NA and t-tau and p-tau may indicate that neurodegeneration affects dual-task performance. Longitudinal studies are needed to further explore dual-task testing in screening for cognitive impairment due to neurodegeneration.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Cognição , Atividade Motora , Degeneração Neural/diagnóstico , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
9.
J Alzheimers Dis ; 67(2): 639-651, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30614806

RESUMO

BACKGROUND: Alzheimer's disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: Aß42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD. OBJECTIVE: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects. METHODS: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4-9 years and 21 of these converted to AD, whereas 53 remained stable. RESULTS: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCI/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively. CONCLUSIONS: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Demência Frontotemporal/líquido cefalorraquidiano , Demência Frontotemporal/diagnóstico , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteoma , Sensibilidade e Especificidade , Proteínas tau/líquido cefalorraquidiano
11.
Am J Nucl Med Mol Imaging ; 8(4): 239-246, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30245916

RESUMO

Neuroimaging is a central part of diagnostic work-up of patients with suspected neurodegenerative disease. FDG-PET can reveal pathological changes earlier and more reliably than morphological imaging. Diagnostic accuracy can be improved by constructing 3D SSP Z-score maps, showing patterns of significant deficits. During FDG-PET, the subject receives a moderate but not insignificant dose of ionizing radiation, and a dose reduction with retained image quality is desirable. With lower dose, repeated examinations can become a useful tool for monitoring disease progress and potential effects of disease-modifying interventions. The aim of this study was to evaluate Z-maps created from low-dose and normal-dose FDG-PET of the brain, with quantitative and qualitative methods. Nine patients with neurodegenerative disorders were prospectively enrolled and nine age-matched controls were recruited through advertising. All subjects (n=18) underwent two FDG-PET scans on separate occasions; a routine and a low-dose scan. The routine dosage of FDG was 3 MBq/kg, and low dosage was 0.75 MBq/kg. 3D-SSP images showing Z-scores of < -1.96 were created from 10-minute summations. The study was comprised of a quantitative part comparing the Z-scores, and a qualitative part where experienced nuclear medicine specialists visually assessed the images. Regarding the quantitative part, Bland-Altman analysis showed a slight constant bias (0.206). Regarding qualitative discrimination between patients and controls, the performance between normal- and low-dose were equal, both showing 72% sensitivity, 83% specificity and 78% accuracy. In this study, visual assessment of 3D-SSP Z-score maps from low-dose FDG-PET provided diagnostic information highly comparable to normal-dose, with minor quantitative discrepancies.

12.
Front Aging Neurosci ; 10: 217, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30061827

RESUMO

Background and Purpose: Signs of small vessel disease (SVD) are commonly seen on magnetic resonance imaging (MRI) of the brain in cognitively healthy elderly individuals, and the clinical relevance of these are often unclear. We have previously described three different MRI manifestations of SVD as well as cerebral perfusion in a longitudinal study of non-demented 75-year-old subjects. The purpose of the present study was to evaluate the relationship of these findings to cognition and executive function at age 75 and changes after 5 years. Methods: In all, 406 subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study were examined with MRI of the brain at age 75 years. Two-hundred and fifty of the subjects were re-examined 5 years later. White matter hyperintensities (WMHs) and lacunar infarcts (LIs) were assessed on both occasions, but microbleeds (MBs) and perfusion only at age 75. Cognitive function was screened by the Mini Mental State Examination (MMSE). Trail Making Test A and B (TMT-A and TMT-B) were performed at baseline and at follow-up at age 80. Results: At baseline, 93% performed >27 points in the MMSE. The TMT-B at age 75 was significantly related to WMH visual scoring after adjustment for sex, education and cerebrovascular disease risk factors (+80 s (95% CI 0.3-161 s), P < 0.05 for grade 2-3 vs. grade 0). Neither MMSE nor TMT-A was significantly related to WMH scoring. There was no relation between any test performance and WMH volume, white matter volume, number of MBs or brain perfusion at age 75. Subjects who had sustained a new LI (n = 26) showed a greater increase of the time to perform TMT-A at the 5-year follow-up (+25 s vs. +4 s in LI-free subjects, P = 0.003). Changes in MMSE or TMT-A and -B test performance between ages 75 and 80 were not related to changes in WMH scoring or volume during the 5 years follow-up, or to brain perfusion at age 75. Conclusion: In this cognitively healthy community-based population, moderate-severe WMHs and incident LIs on brain MRI in individuals aged 75-80 years were associated with a mild impairment of processing speed and executive function.

13.
Alzheimers Dement ; 14(7): 895-901, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29548722

RESUMO

INTRODUCTION: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied. METHODS: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity. RESULTS: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P = .006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P = .028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders. DISCUSSION: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Demência Vascular/genética , Longevidade/genética , Idoso , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Clin Physiol Funct Imaging ; 38(3): 373-377, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28402078

RESUMO

OBJECTIVE: The aim of this study was to explore whether total atherosclerotic burden is related to future decline in performance on cognitive tests. METHODS: The total atherosclerotic burden (TAS) was assessed by whole-body magnetic resonance angiography (WBMRA) in 305 subjects at age 70 in the study Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS). The mini-mental state examination (MMSE) and trail making tests (TMT) A and B were evaluated at ages 75 and 80 in 190 of those subjects. No subject with a diagnosis of dementia was included in the sample. RESULTS: MMSE did not change during the 5 years of follow-up, while TMT A and B increased by 4 and 7 s, respectively. TAS at age 70 was significantly related to the individual change in TMT B (P<0·0001) between age 75 and 80, when adjusted for sex, education level, TMT B at age 75 and Framingham score at age 70. No such relationship was seen for the change in TMT A (P = 0·10). The relationship between TAS and the change in MMSE was of borderline significance (P = 0·025). CONCLUSION: A relationship was found between the total atherosclerotic burden and future decline in performance on TMT B, highlighting a role of global atherosclerosis in the cognitive decline seen during ageing.


Assuntos
Aterosclerose/diagnóstico por imagem , Transtornos Cognitivos/psicologia , Cognição , Envelhecimento Cognitivo/psicologia , Angiografia por Ressonância Magnética , Imagem Corporal Total/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/complicações , Aterosclerose/patologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Placa Aterosclerótica , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Suécia , Fatores de Tempo
15.
Sci Rep ; 7(1): 13230, 2017 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-29038561

RESUMO

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.


Assuntos
Cognição/fisiologia , Vitamina D/análogos & derivados , Vitaminas/fisiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Vitamina D/sangue , Vitamina D/fisiologia
16.
Neurobiol Aging ; 59: 1-9, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28779628

RESUMO

A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology.


Assuntos
Demência/diagnóstico , Albumina Sérica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Barreira Hematoencefálica/fisiopatologia , Estudos de Coortes , Estudos Transversais , Demência/fisiopatologia , Feminino , Humanos , Filamentos Intermediários , Masculino , Pessoa de Meia-Idade
19.
J Am Geriatr Soc ; 65(9): 1953-1960, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28685810

RESUMO

OBJECTIVES: To examine the longitudinal associations between aging with preserved functionality, i.e. independent aging and survival, and lifestyle variables, dietary pattern and cardiovascular risk factors. DESIGN: Cohort study. SETTING: Uppsala Longitudinal Study of Adult Men, Sweden. PARTICIPANTS: Swedish men (n = 1,104) at a mean age of 71 (range 69.4-74.1) were investigated, 369 of whom were evaluated for independent aging 16 years later, at a mean age of 87 (range 84.8-88.9). MEASUREMENTS: A questionnaire was used to obtain information on lifestyle, including education, living conditions, and physical activity. Adherence to a Mediterranean-like diet was assessed according to a modified Mediterranean Diet Score derived from 7-day food records. Cardiovascular risk factors were measured. Independent aging at a mean age of 87 was defined as lack of diagnosed dementia, a Mini-Mental State Examination score of 25 or greater, not institutionalized, independence in personal activities of daily living, and ability to walk outdoors alone. Complete survival data at age 85 were obtained from the Swedish Cause of Death Register. RESULTS: Fifty-seven percent of the men survived to age 85, and 75% of the participants at a mean age of 87 displayed independent aging. Independent aging was associated with never smoking (vs current) (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.05-4.60) and high (vs low) adherence to a Mediterranean-like diet (OR = 2.69, 95% CI = 1.14-6.80). Normal weight or overweight and waist circumference of 102 cm or less were also associated with independent aging. Similar associations were observed with survival. CONCLUSION: Lifestyle factors such as never smoking, maintaining a healthy diet, and not being obese at age 71 were associated with survival and independent aging at age 85 and older in men.


Assuntos
Envelhecimento , Dieta Mediterrânea , Exercício Físico , Vida Independente , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/prevenção & controle , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco , Inquéritos e Questionários , Suécia
20.
J Alzheimers Dis ; 58(4): 1265-1272, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28550260

RESUMO

BACKGROUND: Many people with Alzheimer's disease (AD) live alone in their own homes. There is a lack of knowledge about whether these individuals receive the same quality of diagnostics and treatment for AD as patients who are cohabiting. OBJECTIVES: To investigate the diagnostic work-up and treatment of community-dwelling AD patients who live alone. METHODS: We performed a cross-sectional cohort study based on data from the Swedish Dementia Registry (SveDem). We studied patients diagnosed with AD between 2007 and 2015 (n = 26,163). Information about drugs and comorbidities was acquired from the Swedish Prescribed Drug Register and the Swedish Patient Register. RESULTS: 11,878 (46%) patients lived alone, primarily older women. After adjusting for confounders, living alone was inversely associated with receiving computed tomography (OR 0.90; 95% CI 0.82-0.99), magnetic resonance imaging (OR 0.91; 95% CI 0.83-0.99), and lumbar puncture (OR 0.86; 95% CI 0.80-0.92). Living alone was also negatively associated with the use of cholinesterase inhibitors (OR 0.81; 95% CI 0.76; 0.87), memantine (OR 0.77; 95% CI 0.72; 0.83), and cardiovascular medication (OR 0.92; 0.86; 0.99). On the other hand, living alone was positively associated with the use of antidepressants (OR 1.15; 95% CI 1.08; 1.22), antipsychotics (OR 1.41; 95% CI 1.25; 1.58), and hypnotics and sedatives (OR 1.09; 95% CI 1.02; 1.17). CONCLUSIONS: Solitary living AD patients do not receive the same extent of care as those who are cohabiting.


Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/psicologia , Sistema de Registros , Condições Sociais , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Antidepressivos , Antipsicóticos/uso terapêutico , Estudos de Coortes , Comorbidade , Demência/epidemiologia , Demência/psicologia , Feminino , Humanos , Vida Independente , Imagem por Ressonância Magnética , Masculino , Suécia/epidemiologia
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