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1.
Neuropsychologia ; 135: 107236, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31654648

RESUMO

The oblique effect (OE) describes the visuospatial advantage for identifying stimuli oriented horizontally or vertically rather than diagonally; little is known about brain aging and the OE. We investigated this relationship using the Judgment of Line Orientation (JLO) in 107 older adults (∼age = 67.8 ± 6.6; 51% female) together with neuropsychological tests of executive functioning (EF), attention/information processing (AIP), and neuroimaging. Only JLO lines falling between 36-54° or 126-144° were considered oblique. To quantify the oblique effect, we calculated z-scores for oblique errors (zOblique = #oblique errors/#oblique lines), and similarly, horizontal + vertical line errors (zHV), and a composite measure of oblique relative to HV errors (zOE). Composite z-scores of EF and AIP reflected domains associated with JLO performance. Graph theory analysis integrated T1-derived volumetry and diffusion MRI-derived white matter tractography into connectivity matrices analyzed for select network properties. Participants produced more zOblique than zHV errors (p < 0.001). Age was not associated with zOE adjusting for sex, education, and MMSE. Similarly adjusted linear regression models revealed that lower EF was associated with a larger oblique effect (p < 0.001). Modular analyses of neural connectivity revealed a differential patterns of network affiliation that varied by high versus low group status determined via median split of zOblique and zHV errors, separately. Older adults exhibit the oblique effect and it is associated with specific cognitive processes and regional brain networks that may facilitate future investigations of visuospatial preference in aging.

2.
Neuroimage ; 196: 152-160, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980900

RESUMO

Cardiovascular disease risk factors (CVD-RFs) are associated with decreased gray and white matter integrity and cognitive impairment in older adults. Less is known regarding the interplay between CVD-RFs, brain structural connectome integrity, and cognition. We examined whether CVD-RFs were associated with measures of tract-based structural connectivity in 94 non-demented/non-depressed older adults and if alterations in connectivity mediated associations between CVD-RFs and cognition. Participants (age = 68.2 years; 52.1% female; 46.8% Black) underwent CVD-RF assessment, MRI, and cognitive evaluation. Framingham 10-year stroke risk (FSRP-10) quantified CVD-RFs. Graph theory analysis integrated T1-derived gray matter regions of interest (ROIs; 23 a-priori ROIs associated with CVD-RFs and dementia), and diffusion MRI-derived white matter tractography into connectivity matrices analyzed for local efficiency and nodal strength. A principal component analysis resulted in three rotated factor scores reflecting executive function (EF; FAS, Trail Making Test (TMT) B-A, Letter-Number Sequencing, Matrix Reasoning); attention/information processing (AIP; TMT-A, TMT-Motor, Digit Symbol); and memory (CVLT-II Trials 1-5 Total, Delayed Free Recall, Recognition Discriminability). Linear regressions between FSRP-10 and connectome ROIs adjusting for word reading, intracranial volume, and white matter hyperintensities revealed negative associations with nodal strength in eight ROIs (p-values<.05) and negative associations with efficiency in two ROIs, and a positive association in one ROI (p-values<.05). There was mediation of bilateral hippocampal strength on FSRP-10 and AIP, and left rostral middle frontal gyrus strength on FSRP-10 and AIP and EF. Stroke risk plays differential roles in connectivity and cognition, suggesting the importance of multi-modal neuroimaging biomarkers in understanding age-related CVD-RF burden and brain-behavior.


Assuntos
Encéfalo/patologia , Doenças Cardiovasculares/complicações , Cognição , Substância Cinzenta/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/psicologia , Conectoma/métodos , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Substância Branca/diagnóstico por imagem
3.
Med Sci Sports Exerc ; 51(8): 1613-1618, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30817720

RESUMO

PURPOSE: Cerebrovascular disease in the form of white matter hyperintensities (WMH) increases with age and is associated separately with sedentary time and reduced kidney function. A better understanding of the relationships among these variables would help clarify whether sedentary time should be considered more closely in older adults at particular levels of kidney function to reduce the risk of WMH. METHODS: We analyzed information from 94 healthy community-dwelling older adults to determine the association of sedentary time and WMH in nondemented, nondepressed older adults, and whether level of kidney function was an effect modifier of the relationship between sedentary time and WMH. Sedentary behavior was measured using the Sedentary Behavior Questionnaire. White matter hyperintensity was assessed using whole-brain 3T magnetic resonance imaging T1- and T2-weighted images. Kidney function was calculated by the epi-chronic kidney disease formula for estimated glomerular filtration rate (eGFR). Exposures or predictors were sedentary time, age, sex, education in years, Framingham stroke risk 10-yr prediction score, and eGFR. The analytical approach was multiple linear regression. RESULTS: Adjusting for age, sex, education in years, Framingham stroke risk 10-yr prediction score, greater sedentary time was associated with greater WMH but this effect was dependent on level of eGFR (sedentary time-eGFR interaction b = -0.0005, P = 0.022). At eGFR values of 69, 81, and 93 mL·min per 1.73 m (the 25th, 50th, and 75th percentiles), sedentary time b coefficients were b = 0.021 (95% confidence interval [CI], 0.011-0.031), b = 0.015 (95% CI, 0.008-0.022), and b = 0.009 (95% CI, 0.003-0.016). The effect weakened linearly as eGFR increased, with no significant association at eGFR ≥97 mL·min per 1.73 m. CONCLUSIONS: Findings suggest that sedentary time is associated with WMH in persons with an eGFR ≤96 mL·min per 1.73 m and that this association is stronger with lower levels of kidney function.


Assuntos
Taxa de Filtração Glomerular , Rim/fisiologia , Comportamento Sedentário , Substância Branca/diagnóstico por imagem , Idoso , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Rim/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo
4.
Brain Imaging Behav ; 2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30852709

RESUMO

Patterns of decreased resting cerebral blood flow (CBF) within the inferior temporal gyri, angular gyri, and posterior cingulate are a feature of aging and Alzheimer's disease (AD) and have shown to be predictive of cognitive decline among older adults. Fitness and physical activity are both associated with many indices of brain health and may positively influence CBF, however, the majority of research to date has examined these measures in isolation, leaving the potential independent associations unknown. The purpose of this study was to determine the unique contributions of fitness and physical activity when predicting CBF in cognitively healthy adults at risk for AD. One hundred participants (63% female) from the Wisconsin Registry for Alzheimer's Prevention underwent a maximal exercise test, physical activity monitoring, and a 3-D arterial spin labeling magnetic resonance imaging scan. For the entire sample, fitness was significantly associated with CBF while accounting for physical activity, age, gender, APOE ε4, family history of AD, education, and handedness (p = .026). Further, fitness explained significantly more variance than the combined effect of the covariates on CBF (R2 change = .059; p = .047). These results appear to be gender dependent, our data suggest fitness level, independent of physical activity, is associated with greater CBF in regions that are known to decline with age and AD for female (p = .011), but not male participants.

5.
J Alzheimers Dis ; 58(4): 1089-1097, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28527205

RESUMO

The objective of this study was to investigate the relationship between accelerometer-measured physical activity (PA) and glucose metabolism in asymptomatic late-middle-aged adults. Ninety-three cognitively healthy late-middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention participated in this cross-sectional study. They underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and wore an accelerometer (ActiGraph GT3X+) to measure free-living PA. Accelerometer data yielded measures of light (LPA), moderate (MPA), and vigorous (VPA) intensity PA. FDG-PET images were scaled to the cerebellum and pons, and cerebral glucose metabolic rate was extracted from specific regions of interest (ROIs) known to be hypometabolic in AD, i.e., hippocampus, posterior cingulate, inferior temporal cortex, and angular gyrus. Regression analyses were utilized to examine the association between PA and glucose metabolism, while adjusting for potential confounds. There were associations between MPA and glucose metabolism in all ROIs examined. In contrast, LPA was not associated with glucose uptake in any ROI and VPA was only associated with hippocampal FDG uptake. Secondary analyses did not reveal associations between sedentary time and glucose metabolism in any of the ROIs. Exploratory voxel-wise analysis identified additional regions where MPA was significantly associated with glucose metabolism including the precuneus, supramarginal gyrus, amygdala, and middle frontal gyrus. These findings suggest that the intensity of PA is an important contributor to neuronal function in a late-middle-aged cohort, with MPA being the most salient. Prospective studies are necessary for fully elucidating the link between midlife engagement in PA and later life development of AD.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Córtex Cerebral/metabolismo , Exercício/fisiologia , Glucose/metabolismo , Acelerometria , Idoso , Doença de Alzheimer/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Estudos Transversais , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Sistema de Registros
6.
Neurology ; 88(22): 2098-2106, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28468845

RESUMO

OBJECTIVE: To examine the influence of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether ß-amyloid (Aß) burden plays a moderating role in this relationship. METHODS: One thousand twenty-three adults (baseline age 54.94 ± 6.41 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent BDNF genotyping and cognitive assessment at up to 5 time points (average follow-up 6.92 ± 3.22 years). A subset (n = 140) underwent 11C-Pittsburgh compound B (PiB) scanning. Covariate-adjusted mixed-effects regression models were used to elucidate the effect of BDNF on cognitive trajectories in 4 cognitive domains, including verbal learning and memory, speed and flexibility, working memory, and immediate memory. Secondary mixed-effects regression models were conducted to examine whether Aß burden, indexed by composite PiB load, modified any observed BDNF-related cognitive trajectories. RESULTS: Compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory (p = 0.002) and speed and flexibility (p = 0.017). In addition, Aß burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aß burden showed even steeper cognitive decline (p = 0.033). CONCLUSIONS: In a middle-aged cohort with AD risk, carriage of the BDNF Met allele was associated with steeper decline in episodic memory and executive function. This decline was exacerbated by greater Aß burden. These results suggest that the BDNF Val66Met polymorphism may play an important role in cognitive decline and could be considered as a target for novel AD therapeutics.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Transtornos Cognitivos/genética , Predisposição Genética para Doença , Polimorfismo Genético , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/prevenção & controle , Progressão da Doença , Função Executiva , Feminino , Seguimentos , Heterozigoto , Humanos , Masculino , Memória Episódica , Pessoa de Meia-Idade , Sistema de Registros , Wisconsin
7.
Neurology ; 88(17): 1650-1658, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28341646

RESUMO

OBJECTIVE: To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers. METHODS: Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses. They were genotyped for APOE4, CLU, and ABCA7, from which a PRS was calculated for each participant. The participants underwent lumbar puncture for CSF collection. ß-Amyloid 42 (Aß42), Aß40, total tau (t-tau), and phosphorylated tau (p-tau) were quantified by immunoassays, and Aß42/Aß40 and tau/Aß42 ratios were computed. CRF was estimated from a validated equation incorporating sex, age, body mass index, resting heart rate, and self-reported physical activity. Covariate-adjusted regression analyses were used to test for associations between the PRS and CSF biomarkers. In addition, by including a PRS×CRF term in the models, we examined whether these associations were modified by CRF. RESULTS: A higher PRS was associated with lower Aß42/Aß40 (p < 0.001), higher t-tau/Aß42 (p = 0.012), and higher p-tau/Aß42 (p = 0.040). Furthermore, we observed PRS × CRF interactions for Aß42/Aß40 (p = 0.003), t-tau/Aß42 (p = 0.003), and p-tau/Aß42 (p = 0.001). Specifically, the association between the PRS and these CSF biomarkers was diminished in those with higher CRF. CONCLUSIONS: In a late-middle-aged cohort, CRF attenuates the adverse influence of genetic vulnerability on CSF biomarkers. These findings support the notion that increased cardiorespiratory fitness may be beneficial to those at increased genetic risk for AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Aptidão Cardiorrespiratória/fisiologia , Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética , Biomarcadores/líquido cefalorraquidiano , Clusterina/genética , Estudos de Coortes , Estudos Transversais , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosforilação , Sistema de Registros , Risco , Wisconsin , Proteínas tau/líquido cefalorraquidiano
8.
Brain Behav ; 7(3): e00625, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28293467

RESUMO

INTRODUCTION: Cardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer's disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer's disease (AD). METHODS: Eighty-six enrollees from the Wisconsin Registry for Alzheimer's Prevention participated in this study. Participants performed a graded maximal exercise test, underwent a T-1 anatomical magnetic resonance imaging scan, and completed the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: There were no significant relationships between CRF and HV or RAVLT memory scores for the entire sample. When the sample was explored on the basis of gender, CRF was significantly associated with hippocampal volume for women. For men, significant positive associations were observed between CRF and RAVLT memory scores. SUMMARY: These results suggest that CRF may be protective against both hippocampal volume and episodic memory decline in older adults at risk for AD, but that the relationships may be gender specific.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Aptidão Cardiorrespiratória/fisiologia , Hipocampo/diagnóstico por imagem , Memória Episódica , Sistema de Registros , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Fatores Sexuais
9.
J Alzheimers Dis ; 56(1): 351-359, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27911299

RESUMO

The objective of this study was to examine the association of chronotropic response (CR) and heart rate (HR) recovery- two indices of cardiovascular function within the context of a graded exercise test- with cognitive performance in a cognitively healthy, late-middle-aged cohort at risk for Alzheimer's disease (AD). Ninety participants (age = 63.52±5.86 years; 65.6% female) from the Wisconsin Registry for Alzheimer's Prevention participated in this study. They underwent graded exercise testing and a comprehensive neuropsychological assessment that assessed the following four cognitive domains: Immediate Memory, Verbal & Learning Memory, Working Memory, and Speed & Flexibility. Regression analyses, adjusted for age, sex, and education, were used to examine the association between CR, HR recovery, and cognition. We found significant associations between CR and cognitive performance in the domains of Immediate Memory, Verbal Learning & Memory, and Speed & Flexibility. In contrast, HR recovery was not significantly associated with cognitive function. The association between CR and cognition persisted even after controlling for HR recovery. Together, these findings indicatethat, in a cognitively normal, late-middle-aged cohort, CR is a stronger correlate of cognitive performance than HR recovery. Overall, this study reinforces the idea that cardiovascular health plays an important role in cognitive function, specifically in a cohort at risk for AD; and that interventions that promote vascular health may be a viable pathway to preventing or slowing cognitive decline due to AD.


Assuntos
Doença de Alzheimer/complicações , Transtornos Cognitivos/etiologia , Frequência Cardíaca/fisiologia , Transtornos da Memória/etiologia , Adulto , Idoso , Estudos de Coortes , Exercício/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Recuperação de Função Fisiológica/genética , Análise de Regressão , Aprendizagem Verbal
10.
Artigo em Inglês | MEDLINE | ID: mdl-27489874

RESUMO

INTRODUCTION: Physical activity (PA) is associated with brain health in older adults. However, it is unknown whether the current physical activity recommendations (PAR) impart substantive benefit. The objective of this study was to compare temporal lobe volumes between older adults who met PAR and those who did not. METHODS: Ninety-one enrollees from the Wisconsin Registry for Alzheimer's Prevention wore an accelerometer for seven consecutive days to quantify their PA behaviors and underwent a T-1 anatomic magnetic resonance imaging scan. Participants were categorized as either having met PAR or not based on the US Department of Health and Human Services recommendations of 150 minutes of moderate-to-vigorous physical activity per week. RESULTS: Participants who met PAR possessed significantly greater inferior (η(2) P  = .050) and anterior (η(2) P  = .055) temporal lobe volumes compared with those who did not (P < .05). DISCUSSION: Individuals at-risk for AD experience accelerated rates of brain atrophy. These results suggest that regular engagement in PA at or above PAR could attenuate this decline.

11.
J Int Neuropsychol Soc ; 21(10): 841-50, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26581795

RESUMO

The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-ß (Aß)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer's disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer's Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aß42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aß and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aß42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aß burden, that is, increased PiB-PET binding or reduced CSF Aß42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aß-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD.


Assuntos
Amiloide/metabolismo , Transtornos Cognitivos/reabilitação , Aptidão Física/fisiologia , Adulto , Idoso , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Compostos de Anilina/farmacocinética , Transtornos Cognitivos/líquido cefalorraquidiano , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Estudos de Coortes , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Consumo de Oxigênio , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Escalas de Graduação Psiquiátrica , Tiazóis/farmacocinética , Aprendizagem Verbal
12.
Arch Clin Neuropsychol ; 30(7): 634-42, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26156334

RESUMO

Higher occupational attainment has previously been associated with increased Alzheimer's disease (AD) neuropathology when individuals are matched for cognitive function, indicating occupation could provide cognitive reserve. We examined whether occupational complexity (OCC) associates with decreased hippocampal volume and increased whole-brain atrophy given comparable cognitive function in middle-aged adults at risk for AD. Participants (n = 323) underwent structural MRI, cognitive evaluation, and work history assessment. Three complexity ratings (work with data, people, and things) were obtained, averaged across up to 3 reported jobs, weighted by years per job, and summed to create a composite OCC rating. Greater OCC was associated with decreased hippocampal volume and increased whole-brain atrophy when matched for cognitive function; results remained substantively unchanged after adjusting for several demographic, AD risk, vascular, mental health, and socioeconomic characteristics. These findings suggest that, in people at risk for AD, OCC may confer resilience to the adverse effects of neuropathology on cognition.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos/etiologia , Reserva Cognitiva/fisiologia , Emprego , Adulto , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Doenças Cardiovasculares/complicações , Estudos de Coortes , Feminino , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários
13.
JAMA Neurol ; 72(6): 699-706, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25893879

RESUMO

IMPORTANCE: Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology. OBJECTIVE: To investigate whether cognitive reserve (CR) modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional cohort of 268 individuals (211 in a cognitively normal group and 57 in a cognitively impaired group) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which Aß42, total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed. In addition, we computed t-tau/Aß42 and p-tau/Aß42 ratios. Cognitive reserve was indexed by years of education, with 16 or more years taken to confer high reserve. Covariate-adjusted regression analyses were used to test whether the effect of age on CSF biomarkers was modified by CR. The study dates were March 5, 2010, to February 13, 2013. MAIN OUTCOMES AND MEASURES: Cerebrospinal fluid levels of Aß42, t-tau, p-tau, t-tau/Aß42, and p-tau/Aß42. RESULTS: There were significant age × CR interactions for CSF t-tau (ß [SE] = -6.72 [2.84], P = .02), p-tau (ß [SE] = -0.71 [0.27], P = .01), t-tau/Aß42 (ß [SE] = -0.02 [0.01], P = .02), and p-tau/Aß42 (ß [SE] = -0.002 [0.001], P = .004). With advancing age, individuals with high CR exhibited attenuated adverse alterations in these CSF biomarkers compared with individuals with low CR. This attenuation of age effects by CR tended to be more pronounced in the cognitively impaired group compared with the cognitively normal group. There was evidence of a dose-response relationship such that the effect of age on the biomarkers was progressively attenuated given additional years of schooling. CONCLUSIONS AND RELEVANCE: In a sample composed of a cognitively normal group and a cognitively impaired group, higher CR was associated with a diminution of age-related alterations in CSF biomarkers of AD. This suggests one pathway through which CR might favorably alter lifetime risk for symptomatic AD.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Reserva Cognitiva/fisiologia , Fragmentos de Peptídeos/líquido cefalorraquidiano , Sistema de Registros , Proteínas tau/líquido cefalorraquidiano , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Biomarcadores/líquido cefalorraquidiano , Estudos Transversais , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Brain Imaging Behav ; 9(3): 639-49, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25319359

RESUMO

Cardiorespiratory fitness (CRF) is an objective measure of habitual physical activity (PA), and has been linked to increased brain structure and cognition. The gold standard method for measuring CRF is graded exercise testing (GXT), but GXT is not feasible in many settings. The objective of this study was to examine whether a non-exercise estimate of CRF is related to gray matter (GM) volumes, white matter hyperintensities (WMH), cognition, objective and subjective memory function, and mood in a middle-aged cohort at risk for Alzheimer's disease (AD). Three hundred and fifteen cognitively healthy adults (mean age =58.58 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent structural MRI scanning, cognitive testing, anthropometric assessment, venipuncture for laboratory tests, and completed a self-reported PA questionnaire. A subset (n = 85) underwent maximal GXT. CRF was estimated using a previously validated equation incorporating sex, age, body-mass index, resting heart rate, and self-reported PA. Results indicated that the CRF estimate was significantly associated with GXT-derived peak oxygen consumption, validating its use as a non-exercise CRF measure in our sample. Support for this finding was seen in significant associations between the CRF estimate and several cardiovascular risk factors. Higher CRF was associated with greater GM volumes in several AD-relevant brain regions including the hippocampus, amygdala, precuneus, supramarginal gyrus, and rostral middle frontal gyrus. Increased CRF was also associated with lower WMH and better cognitive performance in Verbal Learning & Memory, Speed & Flexibility, and Visuospatial Ability. Lastly, CRF was negatively correlated with self- and informant-reported memory complaints, and depressive symptoms. Together, these findings suggest that habitual participation in physical activity may provide protection for brain structure and cognitive function, thereby decreasing future risk for AD.


Assuntos
Afeto/fisiologia , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Encéfalo/patologia , Cognição/fisiologia , Aptidão Física/fisiologia , Doença de Alzheimer/psicologia , Doenças Cardiovasculares/fisiopatologia , Teste de Esforço , Família , Feminino , Predisposição Genética para Doença , Substância Cinzenta/patologia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão , Aptidão Física/psicologia , Fatores de Risco , Substância Branca/patologia
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