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1.
J Int Neuropsychol Soc ; : 1-9, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664547

RESUMO

OBJECTIVES: To identify novel associations between modifiable physical and health variables, Alzheimer's disease (AD) biomarkers, and cognitive function in a cohort of older adults with Mild Cognitive Impairment (MCI). METHODS: Metrics of cardiometabolic risk, stress, inflammation, neurotrophic/growth factors, AD, and cognition were assessed in 154 MCI participants (Mean age = 74.1 years) from the Alzheimer's Disease Neuroimaging Initiative. Partial Least Squares analysis was employed to examine associations among these physiological variables and cognition. RESULTS: Latent variable 1 revealed a unique combination of AD biomarkers, neurotrophic/growth factors, education, and stress that were significantly associated with specific domains of cognitive function, including episodic memory, executive function, processing speed, and language, representing 45.2% of the cross-block covariance in the data. Age, body mass index, and metrics tapping basic attention or premorbid IQ were not significant. CONCLUSIONS: Our data-driven analysis highlights the significant relationships between metrics associated with AD pathology, neuroprotection, and neuroplasticity, primarily with tasks tapping episodic memory, executive function, processing speed, and verbal fluency rather than more basic tasks that do not require mental manipulation (basic attention and vocabulary). These data also indicate that biological metrics are more strongly associated with episodic memory, executive function, and processing speed than chronological age in older adults with MCI.

2.
J Sports Sci Med ; 20(3): 391-397, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34267577

RESUMO

The purpose of the present study was to examine the influence of an acute bout of high-intensity resistance exercise on measures of cognitive function. Ten men (Mean ± SD: age = 24.4 ± 3.2 yrs; body mass = 85.7 ± 11.8 kg; height = 1.78 ± 0.08 m; 1 repetition maximum (1RM) = 139.0 ± 24.1 kg) gave informed consent and performed a high-intensity 6 sets of 10 repetitions of barbell back squat exercise at 80% 1RM with 2 minutes rest between sets. The Automated Neuropsychological Assessment Metrics (ANAM) was completed to assess various cognitive domains during the familiarization period, immediately before, and immediately after the high-intensity resistance exercise bout. The repeated measures ANOVAs for throughput scores (r·m-1) demonstrated significant mean differences for the Mathematical Processing task (MTH; p < 0.001, η2 p = 0.625) where post hoc pairwise comparisons demonstrated that the post-fatigue throughput (32.0 ± 8.8 r·m-1) was significantly greater than the pre-fatigue (23.8 ± 7.4 r·m-1, p = 0.003, d = 1.01) and the familiarization throughput (26.4 ± 5.3 r·m-1, p = 0.024, d = 0.77). The Coded Substitution-Delay task also demonstrated significant mean differences (CDD; p = 0.027, η2 p = 0.394) with post hoc pairwise comparisons demonstrating that the post-fatigue throughput (49.3 ± 14.4 r·m-1) was significantly less than the pre-fatigue throughput (63.2 ± 9.6 r·m-1, p = 0.011, d = 1.14). The repeated measures ANOVAs for reaction time (ms) demonstrated significant mean differences for MTH (p < 0.001, η2 p = 0.624) where post hoc pairwise comparisons demonstrated that the post-fatigue reaction time (1885.2 ± 582.8 ms) was significantly less than the pre-fatigue (2518.2 ± 884.8 ms, p = 0.005, d = 0.85) and familiarization (2253.7 ± 567.6 ms, p = 0.009, d = 0.64) reaction times. The Go/No-Go task demonstrated significant mean differences (GNG; p = 0.031, η2 p = 0.320) with post hoc pairwise comparisons demonstrating that the post-fatigue (285.9 ± 16.3 ms) was significantly less than the pre-fatigue (298.5 ± 12.1 ms, p = 0.006, d = 0.88) reaction times. High-intensity resistance exercise may elicit domain-specific influences on cognitive function, characterized by the facilitation of simple cognitive tasks and impairments of complex cognitive tasks.


Assuntos
Cognição/fisiologia , Treinamento de Força/métodos , Adulto , Atenção , Frequência Cardíaca , Humanos , Ácido Láctico/sangue , Masculino , Memória , Rememoração Mental , Fadiga Muscular/fisiologia , Força Muscular , Tempo de Reação , Adulto Jovem
3.
Brain Commun ; 3(3): fcab140, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34286271

RESUMO

The ability to carry out instrumental activities of daily living, such as paying bills, remembering appointments and shopping alone decreases with age, yet there are remarkable individual differences in the rate of decline among older adults. Understanding variables associated with a decline in instrumental activities of daily living is critical to providing appropriate intervention to prolong independence. Prior research suggests that cognitive measures, neuroimaging and fluid-based biomarkers predict functional decline. However, a priori selection of variables can lead to the over-valuation of certain variables and exclusion of others that may be predictive. In this study, we used machine learning techniques to select a wide range of baseline variables that best predicted functional decline in two years in individuals from the Alzheimer's Disease Neuroimaging Initiative dataset. The sample included 398 individuals characterized as cognitively normal or mild cognitive impairment. Support vector machine classification algorithms were used to identify the most predictive modality from five different data modality types (demographics, structural MRI, fluorodeoxyglucose-PET, neurocognitive and genetic/fluid-based biomarkers). In addition, variable selection identified individual variables across all modalities that best predicted functional decline in a testing sample. Of the five modalities examined, neurocognitive measures demonstrated the best accuracy in predicting functional decline (accuracy = 74.2%; area under the curve = 0.77), followed by fluorodeoxyglucose-PET (accuracy = 70.8%; area under the curve = 0.66). The individual variables with the greatest discriminatory ability for predicting functional decline included partner report of language in the Everyday Cognition questionnaire, the ADAS13, and activity of the left angular gyrus using fluorodeoxyglucose-PET. These three variables collectively explained 32% of the total variance in functional decline. Taken together, the machine learning model identified novel biomarkers that may be involved in the processing, retrieval, and conceptual integration of semantic information and which predict functional decline two years after assessment. These findings may be used to explore the clinical utility of the Everyday Cognition as a non-invasive, cost and time effective tool to predict future functional decline.

4.
J Gerontol A Biol Sci Med Sci ; 76(8): 1415-1422, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33880516

RESUMO

Body mass index (BMI) is a risk factor for Alzheimer's disease (AD) although the relationship is complex. Obesity in midlife is associated with increased risk for AD, whereas evidence supports both higher and lower BMI increasing risk for AD in late life. This study examined the influence of individual differences in genetic risk for AD to further clarify the relationship between late-life BMI and conversion to AD. Participants included 52 individuals diagnosed as having mild cognitive impairment (MCI) at baseline who converted to AD within 24 months and 52 matched MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. BMI was measured at baseline. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Conditional logistic regression models were run to determine if BMI and polygenic risk predicted conversion to AD. Results showed an interaction between BMI and genetic risk, such that individuals with lower BMI and higher polygenic risk were more likely to convert to AD relative to individuals with higher BMI. These results remained significant after adjusting for cerebrospinal fluid biomarkers of AD. Exploratory sex-stratified analyses revealed this relationship only remained significant in males. These results show that higher genetic risk in the context of lower BMI predicts conversion to AD in the next 24 months, particularly among males. These findings suggest that genetic risk for AD in the context of lower BMI may serve as a prodromal risk factor for future conversion to AD.


Assuntos
Doença de Alzheimer , Índice de Massa Corporal , Disfunção Cognitiva , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Neuroimagem/métodos , Neuroimagem/estatística & dados numéricos , Prognóstico , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologia
5.
J Alzheimers Dis ; 76(2): 591-600, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538837

RESUMO

BACKGROUND: A complex set of interactions between biological, genetic, and environmental factors likely underlies the development of Alzheimer's disease (AD). Identifying which of these factors is most associated with AD is important for early diagnosis and treatment. OBJECTIVE: We sought to examine genetic risk and structural brain volume on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD. METHODS: 686 adults (55-91 years old) completed a 3T MRI scan, baseline cognitive assessments, and biospecimen collection through the Alzheimer's Disease Neuroimaging Initiative. Hierarchical linear regression analyses examined main and interaction effects of medial temporal lobe (MTL) volume and polygenic hazard score (PHS), indicating genetic risk for AD, on a validated episodic memory composite score. RESULTS: Genetic risk moderated the relationship between MTL volume and memory, such that individuals with high PHS and lower hippocampal and entorhinal volume had lower memory composite scores [ΔF (1,677) = 4.057, p = 0.044, ΔR2 = 0.002]. Further analyses showed this effect was driven by the left hippocampus [ΔF(1,677) = 5.256, p = 0.022, ΔR2 = 0.003] and right entorhinal cortex [ΔF (1,677) = 6.078, p = 0.014, ΔR2 = 0.003]. CONCLUSIONS: Among those with high genetic risk for AD, lower volume was associated with poorer memory. Results suggest that the interaction between AD genetic risk and MTL volume increases the likelihood for memory impairment among older adults. Results from this study suggest that genetic risk and brain volume should be considered key factors in tracking cognitive decline.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Predisposição Genética para Doença/genética , Memória Episódica , Desempenho Psicomotor/fisiologia , Lobo Temporal/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologia , Tomografia por Emissão de Pósitrons/métodos , Lobo Temporal/metabolismo
6.
Mil Med ; 185(5-6): e592-e596, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32060558

RESUMO

INTRODUCTION: Post-traumatic stress disorder (PTSD) is associated with an increased risk of cardiovascular and metabolic diseases and physical inactivity. Cardiorespiratory fitness (CRF), which is modifiable by physical activity, is a strong independent predictor of cardiometabolic health. However, the relationship between CRF and cardiometabolic health in veterans with PTSD is unknown. Thus, this study aimed to explore the cross-sectional relationships among CRF, indices of cardiometabolic health (ie, HbA1c, blood lipids, blood pressure, waist-hip ratio, and body mass index), and PTSD severity in veterans with PTSD. MATERIALS AND METHODS: This study was approved by the local Institutional Review Board. All participants were informed of the study risks and provided consent prior to participation. Participants (n = 13) completed a cardiopulmonary exercise test, a fasting blood draw, and the Clinician Administered PTSD Scale. Correlations between CRF and cardiometabolic health were examined with Spearman's rank correlations, and differences in PTSD symptom severity were explored as a function of CRF (ie, low-to-moderate vs. high CRF), using multiple linear regression. RESULTS: Peak oxygen uptake ($\dot{\mathrm{V}}$O2peak) was correlated with high-density lipoproteins rho = 0.60, P = 0.04 and diastolic blood pressure rho = -0.56, P = 0.05. Ventilatory threshold was correlated with HbA1c rho = -0.61, P = 0.03 and diastolic blood pressure rho = -0.56, P = 0.05. Higher CRF was associated with lower total PTSD severity standardized ß = -0.84, P = 0.01, adjusted R2 = 0.47, total Cluster C symptoms (avoidance/numbing) ß = -0.71, P = 0.02, adjusted R2 = 0.49, and total Cluster D symptoms (hyperarousal) ß = -0.89, P = 0.01, adjusted R2 = 0.41, while adjusting for age and smoking status. CONCLUSIONS: These preliminary findings suggest that CRF and by proxy physical activity may be important factors in understanding the increased risk of cardiovascular and metabolic disease associated with PTSD.


Assuntos
Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Humanos , Masculino , Aptidão Física , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/epidemiologia
7.
Neuroimage Clin ; 25: 102156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31927127

RESUMO

Body mass index (BMI) has a complex relationship with Alzheimer's disease (AD); in midlife, high BMI is associated with increased risk for AD, whereas the relationship in late-life is still unclear. To clarify the relationship between late-life BMI and risk for AD, this study examined the extent to which genetic predisposition for AD moderates BMI and AD-related biomarker associations. Participants included 126 cognitively normal older adults at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Genetic risk for AD was assessed via polygenic hazard score. AD-related biomarkers assessed were medial temporal lobe volume and cerebrospinal fluid (CSF) biomarkers. Hierarchical linear regressions were implemented to examine the effects of BMI and polygenic hazard score on AD-related biomarkers. Results showed that BMI moderated the relationship between genetic risk for AD and medial temporal lobe volume, such that individuals with high BMI and high genetic risk for AD showed lower volume in the entorhinal cortex and hippocampus. In sex-stratified analyses, these results remained significant only in females. Finally, BMI and genetic risk for AD were independently associated with CSF biomarkers of AD. These results provide evidence that high BMI is associated with lower volume in AD-vulnerable brain regions in individuals at genetic risk for AD, particularly females. The genetic pathways of AD may be exacerbated by high BMI. Environmental and genetic risk factors rarely occur in isolation, which underscores the importance of looking at their synergistic effects, as they provide insight into early risk factors for AD that prevention methods could target.


Assuntos
Doença de Alzheimer , Índice de Massa Corporal , Córtex Entorrinal/patologia , Predisposição Genética para Doença , Hipocampo/patologia , Lobo Temporal/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Atrofia/patologia , Biomarcadores , Córtex Entorrinal/diagnóstico por imagem , Feminino , Predisposição Genética para Doença/genética , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Fatores Sexuais , Lobo Temporal/diagnóstico por imagem
8.
Front Psychiatry ; 10: 133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949075

RESUMO

Posttraumatic stress disorder (PTSD) is a prominent mental health problem in veteran and community populations. There is accumulating evidence to suggest that aerobic exercise may serve as an effective treatment option for individuals with PTSD. The purpose of this review is to summarize the existing literature exploring aerobic exercise and PTSD and briefly discuss potential mechanisms of PTSD symptom reduction. A search of electronic databases and reference sections of relevant articles published through October 1, 2018 revealed 19 relevant studies that examined aerobic exercise and PTSD symptomatology. A narrative review of extant studies provides encouraging evidence that aerobic exercise interventions alone or as an adjunct to standard treatment may positively impact PTSD symptoms. Potential mechanisms by which aerobic exercise could exert a positive impact in PTSD include exposure and desensitization to internal arousal cues, enhanced cognitive function, exercise-induced neuroplasticity, normalization of hypothalamic pituitary axis (HPA) function, and reductions in inflammatory markers. Randomized clinical trials and translational neuroscience approaches are required to clarify the efficacy of exercise intervention for PTSD and elucidate potential mechanisms of exercise-induced PTSD symptom reduction.

9.
J Psychiatr Res ; 112: 30-37, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30844595

RESUMO

Previous work has shown that healthy individuals can actively suppress emotional memories through recruitment of the lateral prefrontal cortex. By contrast, individuals with posttraumatic stress disorder (PTSD) frequently experience unwanted memories of their traumatic experiences, even when making explicit efforts to avoid them. However, little is known regarding the behavioral and neural effects of memory suppression among individuals with PTSD. We examined memory suppression associated with PTSD using the Think-No-Think paradigm in an event-related functional magnetic resonance imaging (fMRI) study. We studied three groups: PTSD (n = 16), trauma exposure without PTSD (n = 19), and controls (i.e., no trauma exposure or PTSD; n = 13). There was a main effect of memory suppression such that participants remembered fewer face-picture pairs during the suppress condition than the remember condition. However, trauma-exposed participants (regardless of PTSD status) were less likely to successfully suppress memory than non-trauma-exposed controls. Neuroimaging data revealed that trauma-exposed individuals showed reduced activation in the right middle frontal gyrus during memory suppression. These results suggest that trauma exposure is associated with neural and behavioral disruptions in memory suppression and point to the possibility that difficulty in active suppression of memories may be just one of several likely factors contributing to the development of PTSD.


Assuntos
Afeto/fisiologia , Aprendizagem por Associação/fisiologia , Neuroimagem Funcional , Rememoração Mental/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Córtex Pré-Frontal/fisiopatologia , Trauma Psicológico/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
10.
Cogn Affect Behav Neurosci ; 19(3): 523-536, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30767129

RESUMO

Recent evidence suggests that the human hippocampus-known primarily for its involvement in episodic memory-plays a role in a host of motivationally relevant behaviors, including some forms of value-based decision-making. However, less is known about the role of the hippocampus in value-based learning. Such learning is typically associated with a striatal system, yet a small number of studies, both in human and nonhuman species, suggest hippocampal engagement. It is not clear, however, whether this engagement is necessary for such learning. In the present study, we used both functional MRI (fMRI) and lesion-based neuropsychological methods to clarify hippocampal contributions to value-based learning. In Experiment 1, healthy participants were scanned while learning value-based contingencies (whether players in a "game" win money) in the context of a probabilistic learning task. Here, we observed recruitment of the hippocampus, in addition to the expected ventral striatal (nucleus accumbens) activation that typically accompanies such learning. In Experiment 2, we administered this task to amnesic patients with medial temporal lobe damage and to healthy controls. Amnesic patients, including those with damage circumscribed to the hippocampus, failed to acquire value-based contingencies, thus confirming that hippocampal engagement is necessary for task performance. Control experiments established that this impairment was not due to perceptual demands or memory load. Future research is needed to clarify the mechanisms by which the hippocampus contributes to value-based learning, but these findings point to a broader role for the hippocampus in goal-directed behaviors than previously appreciated.


Assuntos
Amnésia/patologia , Amnésia/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiologia , Recompensa , Lobo Temporal/patologia , Adulto , Idoso , Amnésia/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiologia , Aprendizagem por Probabilidade , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-28435932

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder characterized by debilitating re-experiencing, avoidance, and hyperarousal symptoms following trauma exposure. Recent evidence suggests that individuals with PTSD show disrupted functional connectivity in the default mode network, an intrinsic network that consists of a midline core, a medial temporal lobe (MTL) subsystem, and a dorsomedial prefrontal cortex (dMPFC) subsystem. The present study examined whether functional connectivity in these subsystems is differentially disrupted in PTSD. METHODS: Sixty-nine returning war Veterans with PTSD and 44 trauma-exposed Veterans without PTSD underwent resting state functional MRI (rs-fMRI). To examine functional connectivity, seeds were placed in the core hubs of the default mode network, namely the posterior cingulate cortex (PCC) and anterior medial PFC (aMPFC), and in each subsystem. RESULTS: Compared to controls, individuals with PTSD had reduced functional connectivity between the PCC and the hippocampus, a region of the MTL subsystem. Groups did not differ in connectivity between the PCC and dMPFC subsystem or between the aMPFC and any region within either subsystem. In the PTSD group, connectivity between the PCC and hippocampus was negatively associated with avoidance/numbing symptoms. Examination of the MTL and dMPFC subsystems revealed reduced anticorrelation between the ventromedial PFC (vMPFC) seed of the MTL subsystem and the dorsal anterior cingulate cortex in the PTSD group. CONCLUSIONS: Our results suggest that selective alterations in functional connectivity in the MTL subsystem of the default mode network in PTSD may be an important factor in PTSD pathology and symptomatology.

12.
J Psychiatry Neurosci ; 42(2): 95-102, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28234210

RESUMO

BACKGROUND: Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. METHODS: Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. RESULTS: We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. LIMITATIONS: The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. CONCLUSION: Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.


Assuntos
Catecol O-Metiltransferase/genética , Predisposição Genética para Doença , Hipocampo/diagnóstico por imagem , Polimorfismo Genético , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Estudos Transversais , Feminino , Técnicas de Genotipagem , Humanos , Imageamento Tridimensional , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Reconhecimento Automatizado de Padrão , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Triazinas
13.
Cortex ; 91: 208-220, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28161031

RESUMO

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO2) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis.


Assuntos
Encéfalo/fisiologia , Aptidão Cardiorrespiratória/psicologia , Imageamento por Ressonância Magnética , Memória/fisiologia , Idoso , Envelhecimento , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Aprendizagem Verbal/fisiologia
14.
Brain ; 140(3): 813-825, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28077398

RESUMO

Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease.


Assuntos
Doença de Alzheimer/patologia , Lesões Encefálicas Traumáticas/patologia , Córtex Cerebral/patologia , Adulto , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Estudos Transversais , Progressão da Doença , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único/genética , Escalas de Graduação Psiquiátrica , Análise de Regressão , Fatores de Risco , Veteranos , Adulto Jovem
15.
Neuroimage ; 146: 1084-1092, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27989841

RESUMO

Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO2), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy.


Assuntos
Envelhecimento , Aptidão Cardiorrespiratória , Córtex Cerebral/anatomia & histologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
J Gerontol B Psychol Sci Soc Sci ; 71(3): 474-82, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25528256

RESUMO

OBJECTIVES: Aging is associated with declines in executive function and episodic memory. Cardiorespiratory fitness (CRF) has been associated with enhanced executive function in older adults (OA), but the relationship with episodic memory remains unclear. The purpose of the study was to examine the relationship between CRF and cognition in young and OA and whether CRF mitigates age-related cognitive decline. METHODS: Participants completed exercise testing to evaluate CRF (peak VO2) and neuropsychological testing to assess cognition. RESULTS: In OA, peak VO2 was positively related to executive function, as well as to accuracy on an experimental face-name memory task and visual episodic memory. In young adults (YA), a relationship between peak VO2 and cognition was not evident. High-fit OA performed as well as YA on executive function measures. On episodic memory measures, YA performed better than high-fit OA, who in turn performed better than low-fit OA. CONCLUSIONS: CRF is positively associated with executive function and episodic memory in OA and attenuates age-related cognitive decline. We provide preliminary support for the age-dependence hypothesis, which posits that cognition and CRF relationships may be most readily observed during lifetime periods of significant neurocognitive development.


Assuntos
Envelhecimento/psicologia , Cognição , Função Executiva , Memória Episódica , Aptidão Física , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/prevenção & controle , Transtornos Cognitivos/psicologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estatística como Assunto , Adulto Jovem
17.
J Int Neuropsychol Soc ; 21(10): 780-90, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26581790

RESUMO

Aging is associated with performance reductions in executive function and episodic memory, although there is substantial individual variability in cognition among older adults. One factor that may be positively associated with cognition in aging is physical activity. To date, few studies have objectively assessed physical activity in young and older adults, and examined whether physical activity is differentially associated with cognition in aging. Young (n=29, age 18-31 years) and older adults (n=31, ages 55-82 years) completed standardized neuropsychological testing to assess executive function and episodic memory capacities. An experimental face-name relational memory task was administered to augment assessment of episodic memory. Physical activity (total step count and step rate) was objectively assessed using an accelerometer, and hierarchical regressions were used to evaluate relationships between cognition and physical activity. Older adults performed more poorly on tasks of executive function and episodic memory. Physical activity was positively associated with a composite measure of visual episodic memory and face-name memory accuracy in older adults. Physical activity associations with cognition were independent of sedentary behavior, which was negatively correlated with memory performance. Physical activity was not associated with cognitive performance in younger adults. Physical activity is positively associated with episodic memory performance in aging. The relationship appears to be strongest for face-name relational memory and visual episodic memory, likely attributable to the fact that these tasks make strong demands on the hippocampus. The results suggest that physical activity relates to cognition in older, but not younger adults.


Assuntos
Envelhecimento/fisiologia , Função Executiva/fisiologia , Memória Episódica , Atividade Motora/fisiologia , Acelerometria , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aprendizagem por Associação , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto Jovem
18.
Ann Clin Transl Neurol ; 2(6): 688-98, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26125043

RESUMO

OBJECTIVE: Aging is associated with reduced neural integrity, yet there are remarkable individual differences in brain health among older adults (OA). One factor that may attenuate age-related neural decline is cardiorespiratory fitness (CRF). The primary aim of this study was to link CRF to neural white matter microstructure using diffusion tensor imaging in OA. METHODS: Young adults (YA; n = 32) and OA (n = 27) completed a graded maximal exercise test to evaluate CRF and diffusion tensor magnetic resonance imaging to examine neural white matter integrity. RESULTS: As expected, pervasive age-related declines in white matter integrity were observed when OA were compared to YA. Further, peak VO2 was positively associated with fractional anisotropy (FA), an indicator of white matter integrity, in multiple brain regions in OA, but not YA. In multiple posterior regions such as the splenium, sagittal stratum, posterior corona radiata, and superior parietal white matter, FA values were similar in YA and OA classified as higher fit, with both groups having greater FA than lower fit OA. However, age-related differences in FA values remained in other regions, including the body and genu of the corpus callosum, precuneus, and superior frontal gyrus. INTERPRETATION: CRF is positively associated with neural white matter microstructure in aging. The relationship between peak VO2 and FA appears to be tract-specific, as equivalent FA values were observed in higher fit OA and YA in some white matter tracts, but not others. Further, the association between peak VO2 and FA appears to be age-dependent.

19.
Heart Fail Rev ; 20(5): 561-71, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25896528

RESUMO

Cardiovascular disease is a recognized contributor to the pathogenesis of Alzheimer's disease (AD). Heart failure (HF) is a cardiovascular subtype that can be used to model the contribution of cardiovascular disease to AD. Neuroimaging research indicates that HF patients exhibit a diverse range of structural brain alterations and epidemiological studies suggest HF may be an important risk factor for AD. The neural alterations observed in HF may overlap with those observed in AD and contribute to increased risk of AD in HF patients. To examine this possibility, we reviewed structural MRI studies in persons with HF. We examined subcortical brain regions affected in the early stages of AD (medial temporal lobes), as well as cortical alterations that typically occur in the later stages of AD. Our review indicates that patients with HF exhibit greater neural atrophy and white matter microstructural alterations of nearly every region of the Papez circuit (e.g., hippocampus, cingulate gyrus, thalamus, mammillary bodies, and fornix), as well-significant alterations in cortical and cerebellar regions. Based on animal research and past work in AD patients, the mechanisms for structural brain changes in HF may stem from reductions in cerebral blood flow subsequent to cardiac deficiency. This review supports the hypothesis that HF may contribute to AD risk via widespread structural brain changes, including many of the same regions affected by AD. Case-controlled prospective neuroimaging studies with long-term follow-ups are needed to clarify the risk of AD in HF and elucidate the neural underpinnings of AD risk in HF.


Assuntos
Doença de Alzheimer , Encéfalo , Insuficiência Cardíaca , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Imagem de Tensor de Difusão/métodos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/psicologia , Humanos , Imageamento por Ressonância Magnética/métodos , Testes Neuropsicológicos , Medição de Risco , Fatores de Risco
20.
J Card Fail ; 21(4): 339-46, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25573830

RESUMO

BACKGROUND: Reduced physical activity (PA) may be one factor that contributes to cognitive decline and dementia in heart failure (HF). Yet, the longitudinal relationship between PA and cognition in HF is poorly understood owing to limitations of past work, including single-time assessments of PA. This is the first study to examine changes in objectively measured PA and cognition over time in HF. METHODS AND RESULTS: At baseline and 12 weeks, 57 HF patients completed psychosocial self-report measures and a neuropsychological battery and wore an accelerometer for 7 days. At baseline, HF patients spent an average of 597.83 (SD 75.91) minutes per day sedentary. Steps per day declined from baseline to the 12-week follow-up; there was also a trend for declines in moderate-vigorous PA. Regression analyses controlling for sex, HF severity, and depressive symptoms showed that decreases in light (P = .08) and moderate-vigorous (P = .04) daily PA emerged as strong predictors of declines in attention/executive function over the 12-week period, but not of memory or language. CONCLUSIONS: Reductions in daily PA predicted acute decline in attention/executive function in HF, but not of memory or language. Modifications to daily PA may attenuate cognitive decline, and prospective studies are needed to test this possibility.


Assuntos
Atenção/fisiologia , Transtornos Cognitivos/etiologia , Cognição/fisiologia , Função Executiva/fisiologia , Insuficiência Cardíaca/fisiopatologia , Atividade Motora/fisiologia , Doença Aguda , Idoso , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Autorrelato
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