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1.
Brain ; 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33742668

RESUMO

The aging brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease (AD), infarcts, and Lewy bodies, account for about 40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline (e.g. limbic predominant age-related TDP-43 encephalopathy [LATE-NC], hippocampal sclerosis, other cerebrovascular conditions). We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. 1,164 deceased participants from two longitudinal clinical-pathologic studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathologic examinations provided 11 pathologic indices, including markers of AD, non-AD neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathologic indices with global cognitive decline, and random change point models examined the relation of the pathologic indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = -0.101, SE = 0.003, p < 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, p < 0.001). When considered separately, 10 of the 11 pathologic indices were associated with faster decline and accounted for between 2 and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathologic indices together accounted for a total of 43% of the variation in decline; AD-related indices accounted for 30-36% of the variation, non-AD neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathologic indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive aging and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.

2.
Parkinsonism Relat Disord ; 84: 105-111, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33607526

RESUMO

INTRODUCTION: Emerging technologies show promise for enhanced characterization of Parkinson's Disease (PD) motor manifestations. We evaluated quantitative mobility measures from a wearable device compared to the conventional motor assessment, the Movement Disorders Society-Unified PD Rating Scale part III (motor MDS-UPDRS). METHODS: We evaluated 176 PD subjects (mean age 65, 65% male, 66% H&Y stage 2) during routine clinic visits using the motor MDS-UPDRS and a 10-min motor protocol with a body-fixed sensor (DynaPort MT, McRoberts BV), including the 32-ft walk, Timed Up and Go (TUG), and standing posture with eyes closed. Regression models examined 12 quantitative mobility measures for associations with (i) motor MDS-UPDRS, (ii) motor subtype (tremor dominant vs. postural instability/gait difficulty), (iii) Montreal Cognitive Assessment (MoCA), and (iv) physical functioning disability (PROMIS-29). All analyses included age, gender, and disease duration as covariates. Models iii-iv were secondarily adjusted for motor MDS-UPDRS. RESULTS: Quantitative mobility measures from gait, TUG transitions, turning, and posture were significantly associated with motor MDS-UPDRS (7 of 12 measures, p < 0.05) and motor subtype (6 of 12 measures, p < 0.05). Compared with motor MDS-UPDRS, several quantitative mobility measures accounted for a 1.5- or 1.9-fold increased variance in either cognition or physical functioning disability, respectively. Among minimally-impaired subjects in the bottom quartile of motor MDS-UPDRS, including subjects with normal gait exam, the measures captured substantial residual motor heterogeneity. CONCLUSION: Clinic-based quantitative mobility assessments using a wearable sensor captured features of motor performance beyond those obtained with the motor MDS-UPDRS and may offer enhanced characterization of disease heterogeneity.

3.
PLoS One ; 16(2): e0245680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529220

RESUMO

BACKGROUND: This study tested the hypothesis that sarcopenia and its constituent components, reduced lean muscle mass and impaired motor function, are associated with reduced survival and increased risk of incident disabilities. METHODS: 1466 community-dwelling older adults underwent assessment of muscle mass with bioelectrical impedance analysis (BIA), grip strength, gait speed and other components of physical frailty and annual self-report assessments of disability. We used Cox proportional hazards models that controlled for age, sex, race, education and height to examine the associations of a continuous sarcopenia metric with the hazard of death and incident disabilities. RESULTS: Mean baseline age was about 80 years old and follow-up was 5.5 years. In a proportional hazards model controlling for age, sex, race, education and baseline sarcopenia, each 1-SD higher score on a continuous sarcopenia scale was associated with lower hazards of death (HR 0.70, 95%CI [0.62, 0.78]), incident IADL (HR 0.80,95%CI [0.70, 0.93]), incident ADL disability (HR 0.80 95%CI [71, 91]) and incident mobility disability (HR 0.81, 95%CI [0.70, 0.93]). Further analyses suggest that grip strength and gait speed rather than muscle mass drive the associations with all four adverse health outcomes. Similar findings were observed when controlling for additional measures used to assess physical frailty including BMI, fatigue and physical activity. CONCLUSIONS: Motor function is the primary driver of the associations of sarcopenia and physical frailty with diverse adverse health outcomes. Further work is needed to identify other facets of muscle structure and motor function which together can identify adults at risk for specific adverse health outcomes.

4.
Hum Brain Mapp ; 42(6): 1794-1804, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33471942

RESUMO

The role of massa intermedia (MI) is poorly understood in humans. Recent studies suggest its presence may play a role in normal human neurocognitive function while prior studies have shown the absence of MI correlated with psychiatric disorders. There is growing evidence that MI is likely a midline white matter conduit, responsible for interhemispheric connectivity, similar to other midline commissures. MI presence was identified in an unrelated sample using the Human Connectome Project database. MI structural connectivity maps were created and gray matter target regions were identified using probabilistic tractography of the whole brain. Probabilistic tractography revealed an extensive network of connections between MI and limbic, frontal and temporal lobes as well as insula and pericalcarine cortices. Women compared to men had stronger connectivity via their MI. The presented results support the role of MI as a midline commissure with strong connectivity to the amygdala, hippocampus, and entorhinal cortex.

5.
Photodermatol Photoimmunol Photomed ; 37(2): 99-104, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33471377

RESUMO

Pellagra is a clinical syndrome caused by a deficiency of niacin (nicotinic acid) and/or its precursor tryptophan. The cardinal manifestations are 4 D's: dermatitis, diarrhoea, dementia and in worst case death. Increased use of isoniazid prophylaxis along with antiretroviral therapy in countries where latent tuberculosis is common has been associated with increased presentations with pellagra.

6.
J Invest Dermatol ; 140(11): 2099-2104.e1, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33099396

RESUMO

UVR exposure is a widely applied technique in clinical and preclinical studies. Such experimental conditions provide crucial information on the biological responses of skin and cell models, which may then be extrapolated and interpreted, for example, in the context of equivalent daylight exposures. It is therefore important to fully understand the characteristics of UVR and the principles behind correct and appropriate UVR exposure in experimental settings. In this Research Techniques Made Simple article, we discuss the relevant background information and the best practices for accurate, transparent, and reproducible experimentation and reporting of UVR exposure.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32931560

RESUMO

BACKGROUND: Wearable sensors are increasingly employed to quantify diverse aspects of mobility. We developed novel tandem walk (TW) metrics, validated these measures using data from community-dwelling older adults and evaluated their association with mobility disability and measures of gait and postural control. METHODS: 693 community-dwelling older adults (age: 78.69±7.12 yrs) wore a 3D-accelerometer on their lower back while performing three tasks: TW, usual-walking, and quiet standing. Six new measures of TW were extracted from the sensor data along with the clinician's conventional assessment of TW missteps (i.e., trip other loss of balance in which recovery occurred to prevent a fall) and duration. Principal component analysis (PCA) transformed the 6 new TW measures into two summary TW composite factors. Logistic regression models evaluated whether these TW factors were independently associated with mobility disability. RESULTS: Both TW factors were moderately related to the TW conventional measures (r<0.454, p<0.001) and were mildly correlated with usual-walking (r<0.195, p<0.001) and standing, postural control (r<0.119, p<0.001). The TW frequency composite factor (p=0.008), but not TW complexity composite factor (p=0.246), was independently associated with mobility disability in a model controlling for age, sex, body-mass-index, race, conventional measures of TW, and other measures of gait and postural control. CONCLUSIONS: Sensor-derived tandem walk metrics expand the characterization of gait and postural control and suggest that they reflect a relatively independent domain of mobility. Further work is needed to determine if these metrics improve risk stratification for other adverse outcomes (e.g., falls and incident disability) in older adults.

10.
PLoS One ; 15(4): e0232404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348372

RESUMO

OBJECTIVE: We examined the association of physical activity, postmortem brain pathologies, and parkinsonism proximate to death in older adults. METHODS: We studied the brains of 447 older decedents participating in a clinical-autopsy cohort study. We deployed a wrist worn activity monitor to record total daily physical activity during everyday living in the community-setting. Parkinsonism was assessed with 26 items of a modified motor portion of Unified Parkinson's Disease Rating Scale (UPDRS). We used linear regression models, controlling for age and sex, to examine the association of physical activity with parkinsonism with and without indices of Alzheimer's disease and related disorders (ADRD) pathologies. In separate models, we added interaction terms to examine if physical activity modified the associations of brain pathologies with parkinsonism. RESULTS: Mean age at death was 90.9 (SD, 6.2), mean severity of parkinsonism was 14.1 (SD, 9.2, Range 0-59.4), and 350 (77%) had evidence of more than one ADRD pathologies. Higher total daily physical activity was associated with less severe parkinsonism (Estimate, -0.315, S.E., 0.052, p<0.001). The association of more physical activity with less severe parkinsonism persisted after adding terms for ten brain pathologies (Estimate, -0.283, S.E., 0.052, p<0.001). The associations of brain pathologies with more severe parkinsonism did not vary with the level of physical activity. CONCLUSION: The association of higher physical activity with less severe parkinsonism may be independent of the presence of ADRD brain pathologies. Further work is needed to identify mechanisms through which physical activity may maintain motor function in older adults.


Assuntos
Encéfalo/patologia , Transtornos Parkinsonianos/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Exercício Físico , Feminino , Humanos , Masculino , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/etiologia , Fatores Sexuais
11.
Neurocrit Care ; 33(2): 552-564, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32072457

RESUMO

BACKGROUND/OBJECTIVE: Diffusion weighted imaging (DWI) lesions have been well described in patients with acute spontaneous intracerebral hemorrhage (sICH). However, there are limited data on the influence of these lesions on sICH functional outcomes. We conducted a prospective observational cohort study with blinded imaging and outcomes assessment to determine the influence of DWI lesions on long-term outcomes in patients with acute sICH. We hypothesized that DWI lesions are associated with worse modified Rankin Scale (mRS) at 3 months after hospital discharge. METHODS: Consecutive sICH patients meeting study criteria were consented for an magnetic resonance imaging (MRI) scan of the brain and evaluated for remote DWI lesions by neuroradiologists blinded to the patients' hospital course. Blinded mRS outcomes were obtained at 3 months. Logistic regression was used to determine significant factors (p < 0.05) associated with worse functional outcomes defined as an mRS of 4-6. The generalized estimating equation (GEE) approach was used to investigate the effect of DWI lesions on dichotomized mRS (0-3 vs 4-6) longitudinally. RESULTS: DWI lesions were found in 60 of 121 patients (49.6%). The presence of a DWI lesion was associated with increased odds for an mRS of 4-6 at 3 months (OR 5.987, 95% CI 1.409-25.435, p = 0.015) in logistic regression. Using the GEE model, patients with a DWI lesion were less likely to recover over time between 14 days/discharge and 3 months (p = 0.005). CONCLUSIONS: DWI lesions are common in primary sICH, occurring in almost half of our cohort. Our data suggest that DWI lesions are associated with worse mRS at 3 months in good grade sICH and are predictive of impaired recovery after hospital discharge. Further research into the pathophysiologic mechanisms underlying DWI lesions may lead to novel treatment options that may improve outcomes associated with this devastating disease.

12.
J Orthop Res ; 38(9): 2050-2056, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31976569

RESUMO

The objective of this study was to validate three-dimensional (3D) proximal femoral surface models generated from a 1.5 T magnetic resonance imaging (MRI) by comparing these 3D models to those derived from the clinical "gold standard" of computed tomography (CT) scan and to ground-truth surface models obtained by laser scans (LSs) of the excised femurs. Four intact bilateral cadaveric pelvis specimens underwent CT and MRI scans and 3D surface models were generated. Six femurs were extracted from these specimens, and the overlying soft tissues were removed. The extracted femurs were then laser scanned to produce a ground-truth surface model. A 3D-3D registration method was used to compare the signed and absolute surface-to-surface distances between the 3D models. Absolute agreement was evaluated using a 95% confidence interval (CI) derived from the precision of the LS ground-truth. Paired samples t tests and Kolmogrov-Smirnov tests were performed to compare the differences between the signed and absolute surface-to-surface distances between the models. The average signed surface-to-surface distances for the MRI vs LS and MRI vs CT models were 0.07 and 0.16 mm, respectively. These differences fell within the 95% CI of ±0.20 mm indicating absolute agreement between the surface models generated from these modalities. The signed surface-to-surface distance was significantly smaller for MRI vs LS ground truth model as compared with the CT vs LS model. Femoral models derived from a 1.5 T MRI scan demonstrated absolute agreement with the clinical gold standard of CT-derived models and were most like LS ground truth models of the excised femurs.

13.
Alzheimers Dement ; 16(1): 209-218, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914231

RESUMO

INTRODUCTION: Reduced hippocampal volume is associated with late-life cognitive decline, but prior studies have not determined whether this association persists after accounting for Alzheimer's disease (AD) and other neuropathologies. METHODS: Participants were 531 deceased older adults from community-based cohort studies of aging who had undergone annual cognitive evaluations. At death, brain tissue underwent neuropathologic examination and magnetic resonance imaging (MRI). Linear mixed models examined whether hippocampal volume measured via MRI accounted for variation in decline rate of global cognition and five cognitive domains, above and beyond neuropathologic indices. RESULTS: Demographics and indices of AD, cerebrovascular disease, Lewy body disease, hippocampal sclerosis, TDP-43, and atherosclerosis accounted for 42.6% of the variation in global cognitive decline. Hippocampal volume accounted for an additional 5.4% of this variation and made similar contributions in four of the five cognitive domains. DISCUSSION: Hippocampal volume is associated with late-life cognitive decline, above and beyond contributions from common neuropathologic indices.


Assuntos
Envelhecimento , Disfunção Cognitiva/patologia , Hipocampo/patologia , Neuropatologia , Idoso , Envelhecimento/patologia , Encéfalo/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Lobo Temporal/patologia
14.
Neurology ; 94(2): e142-e152, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31757868

RESUMO

OBJECTIVE: To investigate the contribution of Alzheimer disease (AD) vs non-AD neuropathologies to hippocampal atrophy. METHODS: The Religious Orders Study and Rush Memory and Aging Project are clinicopathologic cohort studies of aging. The current study included 547 participants who had undergone brain autopsy and postmortem hippocampal volume measurement by November 1, 2018. Hippocampal volume was measured with postmortem MRI via a 3D region of interest applied to the hippocampal formation. Neuropathologies were measured via uniform structured evaluations. Linear regression analyses estimated the proportion of variance of hippocampal volume attributable to AD and non-AD neuropathologies. RESULTS: The average age at death was 90 years, and the average hippocampal volume was 2.1 mL. AD, transactive response DNA-binding protein 43 (TDP), hippocampal sclerosis (HS), and atherosclerosis were associated with hippocampal volume. After demographics and total hemisphere volume were controlled for, 7.0% of the variance (95% bootstrapped confidence interval [CI] 4.3%-10.5%) of hippocampal volume was attributable to AD pathology. TDP/HS explained an additional 4.5% (95% CI 2.2%-7.6%). Among individuals with Alzheimer dementia (n = 232), 3.1% (95% CI 0.6%-7.7%) of the variance was attributable to AD pathology, and TDP/HS explained an additional 6.1% (95% CI 2.2%-11.6%). Among those without Alzheimer dementia (n = 307), 3.2% (95% CI 0.9%-7.3%) of the variance was attributable to AD pathology, and TDP/HS explained an additional 1.1%, which did not reach statistical significance. Lewy bodies and vascular diseases had modest contribution to the variance of hippocampal volume. CONCLUSIONS: Both AD and TDP/HS contribute to hippocampal volume loss in older-old persons, with TDP/HS more strongly associated with hippocampal volume than AD in Alzheimer dementia.


Assuntos
Doença de Alzheimer/patologia , Hipocampo/patologia , Proteinopatias TDP-43/patologia , Idoso de 80 Anos ou mais , Atrofia , Feminino , Humanos , Masculino , Esclerose
15.
Gait Posture ; 76: 128-135, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31760316

RESUMO

BACKGROUND: Walking is a volitional behavior that requires planning and initiation before a step is observed. Following a signal to begin walking, studies of gait initiation in specialized labs have identified three phases that occur during the transition from a standing position via anticipatory postural adjustment (APA) to the first step. Routine instrumented gait testing outside of the laboratory setting focuses on gait execution and does not include gait initiation measures. RESEARCH QUESTION: Can a single IMU sensor be used for performing gait initiation evaluations outside the lab? METHODS: We recorded walking in young (N = 41) and older (N = 26) adults using an instrumented gait mat while they were wearing a 3D accelerometer on their lower back. Subjects were instructed to begin walking following an auditory signal. An algorithm was developed to extract the following measures from the acceleration signal: gait initiation time, measured from the start of the auditory cue to begin walking and ends at the heel-strike of the swing leg, time-to-APA (reaction time), APA duration and swing time (execution of the first step). RESULTS: Intraclass correlation coefficient analysis showed good to excellent agreement between gait initiation metrics obtained with the gait mat and the wearable sensor (mean 0.88, range [0.75-0.96]). Except for swing time, all measures were longer in the older subjects, compared to the young adults (p < 0.01). SIGNIFICANCE: Extracting gait initiation measures from routine instrumented gait testing may facilitate studies that can better determine the extent to which impaired gait planning and execution contribute to mobility impairments.


Assuntos
Cognição , Marcha , Caminhada , Adulto , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dispositivos Eletrônicos Vestíveis , Adulto Jovem
16.
Photodermatol Photoimmunol Photomed ; 36(2): 90-96, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31518445

RESUMO

BACKGROUND: Although used for decades in psoriasis, access to phototherapy is becoming increasingly restricted. Besides patient inconvenience, this is in large part to do with a perception of "high cost." We previously reported a comprehensive analysis of direct and indirect phototherapy treatment cost. However, no robust data exist on the actual savings associated with providing phototherapy in the treatment pathway. OBJECTIVES: To quantify the cost savings achieved by phototherapy by delaying alternative treatments. METHODS: Costs accruing through the UK-wide established treatment pathway with and without phototherapy were analysed. Direct and indirectly incurred drug treatment costs were calculated using drug tariff, laboratory cost, estate rates and clinic review costs. To enhance reliability, ranges of cost scenarios were calculated by varying parameters such as drug dosing. RESULTS: Medium annual cost savings per patient were £2200 [range: £1800-£2900] for NB-UVB, and £3700 [range: £2500-£5300] if both NB-UVB and PUVA courses were administered, respectively. As the provider treated 656 ± 76 patients per year during the 6-year observational window, this amounted to savings of £Mio 2.4 [range: £Mio 1.6-£Mio 3.4], even excluding additional non-modelled drug-associated costs (eg diagnostics, adverse event management). Since we only consider cost savings by delay of drug treatment for the duration of phototherapy, drug price reductions through biosimilar introduction only have a small effect. We provide spreadsheets allowing adaptation cost savings projections by varying input variables. CONCLUSIONS: Healthcare providers may achieve significant cost savings by implementing and/or widening access to phototherapy.


Assuntos
Redução de Custos , Fototerapia/economia , Psoríase , Tempo para o Tratamento/economia , Custos e Análise de Custo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Psoríase/economia , Reino Unido
17.
J Gerontol A Biol Sci Med Sci ; 75(4): 702-711, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-31046115

RESUMO

BACKGROUND: Physical activity is a modifiable risk factor associated with health benefits. We hypothesized that a more active lifestyle in older adults is associated with a reduced risk of incident parkinsonism and a slower rate of its progression. METHODS: Total daily physical activity was recorded with an activity monitor in 889 community-dwelling older adults participating in the Rush Memory and Aging Project. Four parkinsonian signs were assessed with a modified motor portion of the Unified Parkinson's Disease Rating Scale and summarized as a categorical measure and continuous global parkinsonian score. We used Cox models to determine whether physical activity was associated with incident parkinsonism and linear mixed-effects models to examine if physical activity was associated with the rate of progressive parkinsonism. RESULTS: During an average follow-up of 4 years, 233 of 682 (34%) participants, without parkinsonism, developed incident parkinsonism. In Cox models controlling for age, sex, and education, a higher level of physical activity was associated with a reduced risk of developing parkinsonism (hazard ratio = 0.79; 95% CI = 0.70-0.88, p < .001). This association was not attenuated when controlling for cognition, depressive symptoms, Apolipoprotein E ℇ4 allele, and chronic health conditions. In a linear mixed-effects model including all participants (N = 889) which controlled for age, sex, and education, a 1 SD total daily physical activity was associated with a 20% slower rate of progression of parkinsonism. CONCLUSION: Older adults with a more active lifestyle have a reduced risk for parkinsonism and a slower rate of its progression.

18.
J Gerontol A Biol Sci Med Sci ; 75(6): 1176-1183, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31246244

RESUMO

BACKGROUND: Gait speed is a robust nonspecific predictor of health outcomes. We examined if combinations of gait speed and other mobility metrics are associated with specific health outcomes. METHODS: A sensor (triaxial accelerometer and gyroscope) placed on the lower back, measured mobility in the homes of 1,249 older adults (77% female; 80.0, SD = 7.72 years). Twelve gait scores were extracted from five performances, including (a) walking, (b) transition from sit to stand, (c) transition from stand to sit, (d) turning, and (e) standing posture. Using separate Cox proportional hazards models, we examined which metrics were associated with time to mortality, incident activities of daily living disability, mobility disability, mild cognitive impairment, and Alzheimer's disease dementia. We used a single integrated analytic framework to determine which gait scores survived to predict each outcome. RESULTS: During 3.6 years of follow-up, 10 of the 12 gait scores predicted one or more of the five health outcomes. In further analyses, different combinations of 2-3 gait scores survived backward elimination and were associated with the five outcomes. Sway was one of the three scores that predicted activities of daily living disability but was not included in the final models for other outcomes. Gait speed was included along with other metrics in the final models predicting mortality and activities of daily living disability but not for other outcomes. CONCLUSIONS: When analyzing multiple mobility metrics together, different combinations of mobility metrics are related to specific adverse health outcomes. Digital technology enhances our understanding of impaired mobility and may provide mobility biomarkers that predict distinct health outcomes.

19.
Neurobiol Aging ; 84: 17-25, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31479860

RESUMO

The associations of 4 proteins-AK4, ITPK1, HSPB2, and IGFBP5-with cognitive function in older adults were largely unexplained by known brain pathologies. We examined the extent to which individual protein associations with cognitive decline were attributable to microstructural changes in the brain. This study included 521 participants (mean age 90.3, 65.9-108.3) with the postmortem reciprocal of transverse relaxation time (R2) magnetic resonance image. All participants came from one of the 2 ongoing longitudinal cohorts of aging and dementia, the Religious Orders Study and Rush Memory and Aging Project. Higher abundance of AK4, HSPB2, and IGFBP5 was associated with faster cognitive decline and mediated through lower postmortem R2 in the frontal and temporal white matter regions. In contrast, higher abundance of ITPK1 was associated with slower cognitive decline and mediated through higher postmortem R2 in the frontal and temporal white matter regions. The associations of 4 proteins-AK4, ITPK1, IGFBP5, and HSPB2-with cognition in late life were explained via microstructural changes in the brain.


Assuntos
Adenilato Quinase/genética , Encéfalo/patologia , Disfunção Cognitiva/genética , Estudos de Associação Genética , Proteínas de Choque Térmico HSP27/genética , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Estudos de Coortes , Humanos
20.
Parkinsonism Relat Disord ; 65: 190-196, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31272924

RESUMO

INTRODUCTION: Mobility metrics derived from wearable sensor recordings are associated with parkinsonism in older adults. We examined if these metrics predict incident parkinsonism. METHODS: Parkinsonism was assessed annually in 683 ambulatory, community-dwelling older adults without parkinsonism at baseline. Four parkinsonian signs were derived from a modified Unified Parkinson's Disease Rating Scale (UPDRS). Parkinsonism was based on the presence of 2 or more signs. Participants wore a sensor on their back while performing a 32 foot walk, standing posture, and Timed Up and Go (TUG) tasks. 12 mobility scores were extracted. Cox proportional hazards models with backward elimination were used to identify combinations of mobility scores independently associated with incident parkinsonism. RESULTS: During follow-up of 2.5 years (SD = 1.28), 139 individuals developed parkinsonism (20.4%). In separate models, 6 of 12 mobility scores were individually associated with incident parkinsonism, including: Speed and Regularity (from 32 ft walk), Sway (from standing posture), and 3 scores from TUG subtasks (Posterior sit to stand transition, Range stand to sit transition, and Yaw, a measure of turning efficiency). When all mobility scores were analyzed together in a single model, 2 TUG subtask scores, Range from stand to sit transition (HR, 1.42, 95%CI, 1.09, 1.82) and Yaw from turning (HR, 0.56, 95%CI, 0.42, 0.73) were independently associated with incident parkinsonism. These results were unchanged when controlling for chronic health covariates. CONCLUSION: Mobility metrics derived from a wearable sensor complement conventional gait testing and have potential to enhance risk stratification of older adults who may develop parkinsonism.


Assuntos
Acelerometria , Análise da Marcha , Transtornos Parkinsonianos/diagnóstico , Dispositivos Eletrônicos Vestíveis , Idoso , Idoso de 80 Anos ou mais , Feminino , Monitores de Aptidão Física , Humanos , Estudos Longitudinais , Masculino , Prognóstico
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