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OBJECTIVES: Post-traumatic stress disorder (PTSD) and subjective cognitive decline (SCD) are independent risk factors for Alzheimer's disease (AD) and dementia, but the association of their interaction on AD biomarkers have yet to be characterized. This study aimed to examine the impact of PTSD on the association between SCD and tau and amyloid positron emission tomography (PET) as well as global cognition in older Veterans. METHOD: This study included 87 Vietnam-Era Veterans without dementia (42 with PTSD; 45 without PTSD) from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. All participants had both tau and amyloid PET imaging as well as cognitive testing. SCD was measured using the Everyday Cognition questionnaire. RESULTS: While SCD was associated with tau PET, amyloid PET, and global cognition, PTSD moderated these associations for tau and amyloid PET levels. Specifically, Veterans without PTSD had a stronger positive relationship between SCD and AD biomarkers when compared to those with PTSD. CONCLUSION: Higher SCD was associated with greater tau and amyloid burden and worse cognitive performance across the sample, though the tau and amyloid associations were stronger for Veterans without PTSD. Results highlight the potential benefit of comprehensive clinical assessments including consideration of mental health among older Veterans with SCD to understand the underlying cause of the cognitive concerns. Additionally, more work is needed to understand alternative mechanisms driving SCD in older Veterans with PTSD.
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BACKGROUND: Chronic pain leads to tau accumulation and hippocampal atrophy, which may be moderated through inflammation. In older men, we examined associations of chronic pain with AD-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation. METHODS: Participants were men without dementia. Chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, we measured plasma amyloid-beta (Aß42, n=871), Aß40 (n=887), total tau (t-tau, n=841), and neurofilament light chain (NfL, n=915), and serum high-sensitivity C-reactive protein (hs-CRP, n=968), a marker of systemic inflammation. A subgroup underwent structural MRI to measure hippocampal volume (n=385). Analyses adjusted for medical morbidities, depressive symptoms, and opioid use. RESULTS: Chronic pain related to higher Aß40 (ß=.25, p=.009), but hs-CRP was unrelated to AD-related biomarkers (ps>05). There was a significant interaction such that older men with both chronic pain and higher levels of hs-CRP had higher levels of Aß42 (ß=.36, p=.001) and Aß40 (ß=.29, p=.003). Chronic pain and hs-CRP did not interact to predict levels of Aß42/Aß40, t-tau, or NfL. Furthermore, there were significant interactions such that Aß42 and Aß40 were associated with lower hippocampal volume, particularly when levels of hs-CRP were elevated (hs-CRP*Aß42: ß=-.19, p=.002; hs-CRP*Aß40: ß=-.21, p=.001), regardless of chronic pain status. CONCLUSIONS: Chronic pain was associated with higher plasma Aß, especially when hs-CRP was also elevated. Higher hs-CRP and Aß levels were both related to smaller hippocampal volumes. Chronic pain, when accompanied by systemic inflammation, may elevate risk of neurodegeneration in AD-vulnerable regions.
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INTRODUCTION: Psychiatric conditions such as post-traumatic stress disorder (PTSD) and depression have a two-fold increased dementia risk in Veterans. Prior work has shown that psychiatric factors can both impact cognitive functioning and be early symptoms associated with Alzheimer's disease (AD). Objectively defined subtle cognitive difficulties (Obj-SCD) has been associated with cognitive decline and AD biomarkers. However, Obj-SCD has not yet been investigated in the context of psychiatric disorders. METHODS: A total of 179 cognitively unimpaired Veterans (50-92 years old) underwent a comprehensive neuropsychological evaluation at VA San Diego and a retrospective medical record review. Chi-squared tests compared rates of psychiatric diagnoses in Veterans with and without Obj-SCD. RESULTS: About 21% of the sample was classified as Obj-SCD. Relative to cognitively unimpaired Veterans, Veterans classified as Obj-SCD had higher rates of PTSD, but not higher rates of other psychiatric conditions (e.g., depression). The PTSD findings appear to be driven by measures of cognitive efficiency. CONCLUSION: Elevated rates of PTSD, but not other psychiatric conditions, were observed among Veterans with Obj-SCD. The prevalence and type of subtle cognitive difficulties associated with PTSD in older Veterans demonstrates a need, and informs potential targets, for intervention. Further work is needed to determine mechanisms of subtle cognitive difficulties in older Veterans with PTSD.
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INTRODUCTION: Data-driven neuropsychological methods can identify mild cognitive impairment (MCI) subtypes with stronger associations to dementia risk factors than conventional diagnostic methods. METHODS: Cluster analysis used neuropsychological data from participants without dementia (mean age = 71.6 years) in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (n = 26,255) and the "normal cognition" subsample (n = 16,005). Survival analyses examined MCI or dementia progression. RESULTS: Five clusters were identified: "Optimal" cognitively normal (oCN; 13.2%), "Typical" CN (tCN; 28.0%), Amnestic MCI (aMCI; 25.3%), Mixed MCI-Mild (mMCI-Mild; 20.4%), and Mixed MCI-Severe (mMCI-Severe; 13.0%). Progression to dementia differed across clusters (oCN < tCN < aMCI < mMCI-Mild < mMCI-Severe). Cluster analysis identified more MCI cases than consensus diagnosis. In the "normal cognition" subsample, five clusters emerged: High-All Domains (High-All; 16.7%), Low-Attention/Working Memory (Low-WM; 22.1%), Low-Memory (36.3%), Amnestic MCI (16.7%), and Non-amnestic MCI (naMCI; 8.3%), with differing progression rates (High-All < Low-WM = Low-Memory < aMCI < naMCI). DISCUSSION: Our data-driven methods outperformed consensus diagnosis by providing more precise information about progression risk and revealing heterogeneity in cognition and progression risk within the NACC "normal cognition" group.
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Disfunção Cognitiva , Progressão da Doença , Testes Neuropsicológicos , Humanos , Disfunção Cognitiva/diagnóstico , Idoso , Feminino , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Análise por Conglomerados , Idoso de 80 Anos ou mais , Fatores de RiscoRESUMO
Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. Objective: This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Methods: Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition. Results: The cluster analysis identified 3 groups. Group 1 (nâ=â128) had average-to-above average cognition with low amyloid burden. Group 2 (nâ=â72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (nâ=â28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. CONCLUSIONS: Psychiatric and health factors likely contributed to Group 2's low memory and language performance. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans' co-morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. These results could have important implications for the implementation of AD-modifying drugs in older Veterans.
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Peptídeos beta-Amiloides , Cognição , Disfunção Cognitiva , Testes Neuropsicológicos , Veteranos , Humanos , Masculino , Veteranos/psicologia , Idoso , Feminino , Estudos Longitudinais , Disfunção Cognitiva/metabolismo , Peptídeos beta-Amiloides/metabolismo , Cognição/fisiologia , Tomografia por Emissão de Pósitrons , Fenótipo , Análise por Conglomerados , Idoso de 80 Anos ou mais , Pessoa de Meia-IdadeRESUMO
Background and Objectives: Consumer credit has shown increasing relevance to the health of older adults; however, studies have not been able to assess the extent to which creditworthiness influences future health or health influences future creditworthiness. We assessed the relationships between 4-year pre and postmorbid consumer credit history and self-rated physical and mental health outcomes among older adults. Research Design and Methods: Generalized estimating equations models assessed pre and postmorbid credit history (credit scores, derogatory accounts, and unpaid accounts in collections) and the onset of poor self-rated health (SF-36 score <50) among 1,740 participants aged 65+ in the Advanced Cognitive Training for Independent and Vital Elderly study from 2001 to 2017, linked to TransUnion consumer credit data. Results: In any given year, up to 1/4 of participants had a major derogatory, unpaid, or collections account, and up to 13% of the sample had poor health. Each 50-point increase in credit score trended toward a 5% lower odds of poor health in the next 1 year, a 6% lower odds in the next 2 years, and a statistically significant finding of 13% lower odds by 3 years. A drop in credit score was associated with a 10% greater odds of poor health in the next year, and having a major derogatory account was associated with an 86% greater odds of poor health in the next 3 years. After poor health onset, credit scores continued to see significant losses up to the 3 years, with larger decrements over time. Discussion and Implications: Having a major derogatory account or a sudden loss in credit may be a time to monitor older adults for changes in health. After a downturn in health, supporting older adults to manage their debt may help stabilize their credit.
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This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE É4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.
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INTRODUCTION: Identification of psychosocial-behavioral phenotypes to understand within-group heterogeneity in risk and resiliency to Alzheimer's disease (AD) within Black/African American and Hispanic/Latino older adults is essential for the implementation of precision health approaches. METHODS: A cluster analysis was performed on baseline measures of socioeconomic resources (annual income, social support, occupational complexity) and psychiatric distress (chronic stress, depression, anxiety) for 1220 racially/ethnically minoritized adults enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD). Analyses of covariance adjusting for sociodemographic factors examined phenotype differences in cognition and plasma AD biomarkers. RESULTS: The cluster analysis identified (1) Low Resource/High Distress (n = 256); (2) High Resource/Low Distress (n = 485); and (3) Low Resource/Low Distress (n = 479) phenotypes. The Low Resource/High Distress phenotype displayed poorer cognition and higher plasma neurofilament light chain; differences between the High Resource/Low Distress and Low Resource/Low Distress phenotypes were minimal. DISCUSSION: The identification of psychosocial-behavioral phenotypes within racially/ethnically minoritized older adults is crucial to the development of targeted AD prevention and intervention efforts.
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Doença de Alzheimer , Negro ou Afro-Americano , Hispânico ou Latino , Idoso , Humanos , Biomarcadores , Cognição , FenótipoRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) affects â¼25% of Veterans, a prevalence rate double that of the general population. T2DM is associated with greater dementia risk and has been shown to exacerbate the impact of Alzheimer's disease (AD) risk factors on declines in daily functioning; however, there are few studies that investigate these patterns in older Veterans. OBJECTIVE: This study sought to determine whether T2DM moderates the association between amyloid-ß (Aß) positron emission tomography (PET) and 1-year change in everyday functioning in older Veterans. METHODS: One-hundred-ninety-eight predominately male Vietnam-Era Veterans without dementia from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DoD-ADNI) with (nâ=â74) and without (nâ=â124) T2DM completed Aß PET imaging and everyday functioning measures, including the Clinical Dementia Rating-Sum of Boxes (CDR-SB) and Everyday Cognition (ECog). Linear mixed effects models tested the moderating role of T2DM on the association between Aß PET and 1-year change in everyday functioning. RESULTS: The 3-way T2DM×Aß PET×time interaction was significant for CDR-SB (pâ<â0.001) as well as the Memory (pâ=â0.007) and Language (pâ=â0.011) subscales from the ECog. Greater amyloid burden was associated with greater increases in functional difficulties, but only in Veterans with T2DM. CONCLUSIONS: Higher Aß was only associated with declines in everyday functioning over 1 year in Veterans with T2DM. Given that people with T2DM are more likely to have co-occurring cerebrovascular disease, the combination of multiple neuropathologies may result in faster declines. Future studies should examine how diabetes duration, severity, and medications impact these associations.
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Doença de Alzheimer , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Veteranos , Humanos , Masculino , Idoso , Doença de Alzheimer/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons/métodosRESUMO
Objectives: The current study examines relationships between Body Mass Index (BMI) and cognitive performance and change in processing speed, memory, and reasoning, while accounting for variations by race and the influence of social determinants of health. Methods: Secondary data analysis of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which included participants who self-identified as African American or Black (n = 728) and White (n = 2028). Latent growth curve modeling was used to assess study aims. Results: Increases in BMI were associated with less cognitive decline over 10 years across each cognition domain. Race moderation effects were noted for speed and memory. Relationships between BMI and cognitive trajectories were mediated by economic stability for speed and reasoning. Discussion: Overall, these findings are consistent with the "obesity paradox." Further research is needed to elucidate patterns of results by race.
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Índice de Massa Corporal , Cognição , Disfunção Cognitiva , Determinantes Sociais da Saúde , Idoso , Humanos , Negro ou Afro-Americano , BrancosRESUMO
OBJECTIVES: We assessed the relationships between pre- and post-morbid consumer credit history (credit scores, debts unpaid, or in collections) and classification of mild (or greater) cognitive impairment (MCI). METHODS: Generalized Estimating Equation models assessed pre-and post-morbid credit history and MCI risk among 1740 participants aged 65+ in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, linked to TransUnion consumer credit data. RESULTS: Each 50-point increase in credit score was associated with up to 8% lower odds of MCI in the next 3 years. In contrast, new unpaid collections over doubled the odds of having MCI in the next 3 years. MCI was associated with subsequent credit score declines and a 47%-71% greater risk of having a new unpaid collection in the next 4 years. DISCUSSION: Credit declines may signal risk for future MCI. MCI may lead to financial challenges that warrant credit monitoring interventions for older adults.
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Disfunção Cognitiva , Treino Cognitivo , Crédito e Cobrança de Pacientes , Idoso , Humanos , Disfunção Cognitiva/psicologiaRESUMO
INTRODUCTION: White matter hyperintensities (WMHs) are magnetic resonance imaging markers of small vessel cerebrovascular disease that are associated with cognitive decline and clinical Alzheimer disease. Previous studies have often focused on global or total WMH; less is known about associations of regional WMHs and cognitive abilities among older adults without dementia. METHODS: A total of 610 older adults with normal cognition (n=302) or mild cognitive impairment (n=308) from the Alzheimer's Disease Neuroimaging Initiative underwent neuropsychological testing and magnetic resonance imaging. Linear regression models examined associations between regional WMH volumes and cognition, adjusting for age, sex, education, apolipoprotein E ε4 allele frequency, and pulse pressure. RESULTS: Among all participants, greater regional WMH volume in all lobes was associated with poorer performance on memory and speed/executive functioning. Among participants with normal cognition, greater temporal and occipital WMH volumes were associated with poorer memory, whereas no regional WMH volumes were associated with speed/executive function. DISCUSSION: Results show that greater regional WMH volume relates to poorer cognitive functioning-even among those with normal cognition. Together with results from previous studies, our findings raise the possibility that WMH may be a useful therapeutic target and/or important effect modifier in treatment or prevention dementia trials.
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Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Cognição , Função ExecutivaRESUMO
OBJECTIVE: This study examined the moderating effect of traumatic brain injury (TBI) history on subjective and objective cognition across multiple cognitive domains. SETTING, PARTICIPANTS, AND DESIGN: Participants included 242 Vietnam-era veterans with a history of no TBI (n = 86), mild TBI (n = 74), or moderate-to-severe TBI (n = 82) from the observational Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DoD-ADNI) study. MAIN MEASURES: Objective cognition was the outcome and was measured using neuropsychological measures in the domains of memory, attention/executive functioning, and language. Subjective cognition was measured using the memory, divided attention, and language subscales from the Everyday Cognition (ECog) measure. TBI severity status was the moderating variable. RESULTS: Veterans with a history of moderate-to-severe TBI had a stronger negative association between subjective and objective attention relative to participants without a TBI (P = .002). Although this association did not differ between mild TBI and no TBI history groups (P = .100), the association between subjective and objective attention for the mild TBI group was intermediate to the no TBI and moderate-to-severe TBI history groups. TBI status did not moderate associations between subjective and objective memory or language. CONCLUSION: Results highlight the importance of assessing subjective and objective cognition in older veterans and the relevance of attention in the context of TBI history. More work is needed to better understand the intersection of TBI and aging and how these factors may be used to guide individualized assessment and treatment approaches for older veterans.
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BACKGROUND: Alzheimer's disease (AD) and cerebrovascular disease are common, co-existing pathologies in older adults. Whether the effects of cerebrovascular disease and AD biomarkers on cognition are additive or synergistic remains unclear. OBJECTIVE: To examine whether white matter hyperintensity (WMH) volume moderates the independent association between each AD biomarker and cognition. METHODS: In 586 older adults without dementia, linear regressions tested the interaction between amyloid-ß (Aß) positron emission tomography (PET) and WMH volume on cognition, independent of tau-PET. We also tested the interaction between tau-PET and WMH volume on cognition, independent of Aß-PET. RESULTS: Adjusting for tau-PET, the quadratic effect of WMH interacted with Aß-PET to impact memory. There was no interaction between either the linear or quadratic effect of WMH and Aß-PET on executive function. There was no interaction between WMH volume and tau-PET on either cognitive measure. CONCLUSION: Results suggest that cerebrovascular lesions act synergistically with Aß to affect memory, independent of tau, highlighting the importance of incorporating vascular pathology into biomarker assessment of AD.
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Doença de Alzheimer , Transtornos Cerebrovasculares , Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Substância Branca/patologia , Proteínas tau/metabolismo , Imageamento por Ressonância Magnética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Tomografia por Emissão de Pósitrons , Transtornos Cerebrovasculares/complicações , Amiloide , Biomarcadores , Disfunção Cognitiva/patologiaRESUMO
Higher cognitive reserve (CR) may offer protection from cognitive changes associated with reduced cerebral blood flow (CBF). We investigated CR as a moderator of the effect of CBF on cognition in older adults with mild cognitive impairment (MCI; N = 46) and those who are cognitively unimpaired (CU; N = 101). Participants underwent arterial spin labeling MRI, which was used to quantify CBF in 4 a priori regions. Estimated verbal intelligence quotient (VIQ) served as a proxy for CR. Multiple linear regressions examined whether VIQ moderated associations between CBF and cognition and whether this differed by cognitive status. Outcomes included memory and language performance. There were 3-way interactions (CBF*VIQ*cognitive status) on category fluency when examining hippocampal, superior frontal, and inferior frontal CBF. Follow-up analyses revealed that, within the MCI but not CU group, there were CBF*VIQ interactions on fluency in all a priori regions examined, where there were stronger, positive associations between CBF and fluency at higher VIQ. Conclusion: In MCI, higher CR plays a role in strengthening CBF-fluency associations.
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Disfunção Cognitiva , Reserva Cognitiva , Humanos , Idoso , Disfunção Cognitiva/psicologia , Cognição/fisiologia , Idioma , Imageamento por Ressonância Magnética , Circulação Cerebrovascular/fisiologiaRESUMO
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity. OBJECTIVE: Given that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies have suggested lower BDNF levels may be a risk factor of diabetic neurovascular complications, we sought to investigate total white matter hyperintensities (WMH) as a moderator of the effect of BDNF on hippocampal volume and cognition. METHODS: Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative (Nâ=â454 including 49 with T2DM and 405 without diabetes) underwent neuropsychological evaluation, magnetic resonance imaging to quantify hippocampal and WMH volumes, and blood draw to assess BDNF. RESULTS: Adjusting for age, sex, and APOE É4 carrier status, there was a significant interaction between total WMH and BDNF on bilateral hippocampal volume in the non-T2DM group (tâ=â2.63, pâ=â0.009). Examination of main effect models with a dichotomous high/low BNDF group revealed a significant main effect for low BDNF (tâ=â-4.98, pâ<â0.001), such that as WMH increased, bilateral hippocampal volume decreased. There was also a significant interaction between total WMH and BDNF on processing speed in the non-T2DM group (tâ=â2.91, pâ=â0.004). There was a significant main effect for low BDNF (tâ=â-3.55, pâ<â0.001) such that as WMH increased, processing speed decreased. The interactions were not significant in the T2DM group. CONCLUSION: These results further elucidate the protective role that BDNF plays on cognition, as well as the cognitive effects of WMH.
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Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Fator Neurotrófico Derivado do Encéfalo , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Velocidade de Processamento , Cognição/fisiologia , Disfunção Cognitiva/psicologia , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Encéfalo/patologiaRESUMO
Biofluid markers of phosphorylated tau181 (p-tau181) are increasingly popular for the detection of early Alzheimer's pathologic changes. However, the differential dynamics of cerebrospinal fluid (CSF) and plasma p-tau181 remain under investigation. We studied 727 participants from the Alzheimer's Disease Neuroimaging Initiative with plasma and CSF p-tau181 data, apolipoprotein (APOE) ε4 carrier status, amyloid positron emission tomography (PET) imaging, and neuropsychological data. Higher levels of plasma and CSF p-tau181 were observed among APOE ε4 carriers. CSF and plasma p-tau181 were significantly associated with memory, and this effect was greater in APOE ε4 carriers. However, whereas CSF p-tau181 was not significantly associated with language or attention/executive function among ε4 carriers or non-carriers, APOE ε4 status moderated the association of plasma p-tau181 with both language and attention/executive function. These findings lend support to the notion that p-tau181 biofluid markers are useful in measuring AD pathologic changes but also suggest that CSF and plasma p-tau181 have unique properties and dynamics that should be considered when using these markers in research and clinical practice.
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Doença de Alzheimer , Apolipoproteína E4 , Humanos , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética , Apolipoproteína E4/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Cognição , Proteínas tau/líquido cefalorraquidianoRESUMO
OBJECTIVES: Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults. METHOD: Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week. RESULTS: Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume. CONCLUSIONS: Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.
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Disfunção Cognitiva , Exercício Físico , Humanos , Idoso , Exercício Físico/fisiologia , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Acelerometria/métodosRESUMO
INTRODUCTION: According to the Movement Disorder Society (MDS), subjective cognitive complaints (SCC) are a diagnostic criterion for PD-mild cognitive impairment (PD-MCI); however, studies often do not incorporate SCC when classifying PD-MCI. This inconsistent use may reflect mixed findings regarding the association between SCC and objective measures of cognitive impairment. Our study aimed to describe the extent that inclusion/exclusion of SCC affects the occurrence of PD-MCI, and if the inclusion of SCC is associated with faster cognitive decline and cerebrospinal fluid markers (CSF) of alpha-synuclein, amyloid beta, total tau, and phophorylated-tau. METHODS: Individuals with PD (N = 358) from the PPMI cohort whom completed measures of neuropsychological performance, subjective cognitive complaints, motor severity, and CSF markers were included. Participants were classified as cognitively normal (CN), PD-MCI with subjective cognitive complaints (PD-MCI + SCC) and PD-MCI without subjective cognitive complaints (PD-MCI -SCC). RESULTS: PD-MCI rates were consistently higher (16.5-19.1%) across the 5 years when SCC was not included in the diagnostic criteria as opposed to when SCC was included (4.4-11.0%). PD-MCI + SCC experienced greater cognitive decline and had significantly higher levels of tau/ab and p-tau/ab relative to both the CN and PD-MCI - SCC groups. CONCLUSIONS: Inconsistent implementation of an SCC requirement in PD-MCI classifications may have important implications in terms of the occurrence of PD-MCI and its prognostic value. Classifying PD-MCI only using neuropsychological cut-off criterion, without regard to SCC, may lead to higher rates of PD-MCI. Inclusions of SCC in PD-MCI criteria in newly diagnosed PD participants may strengthen the ability to detect individuals at risk for future cognitive decline, though it is possible that this decline is related to Alzheimer's disease changes rather than worse PD pathology.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/líquido cefalorraquidiano , Cognição , Biomarcadores/líquido cefalorraquidiano , Testes Neuropsicológicos , Proteínas tau/líquido cefalorraquidianoRESUMO
OBJECTIVE: Cognitive dispersion across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer's disease (AD). However, little is known regarding brain changes underlying cognitive dispersion, and the association of cognitive dispersion with in vivo AD biomarkers and regional cerebral blood flow (CBF) has received limited study. We therefore examined associations among cognitive dispersion, amyloid-beta (Aß) positivity, and regional CBF among older adults free of dementia. METHOD: One hundred and forty-eight Alzheimer's Disease Neuroimaging Initiative (ADNI) participants underwent neuropsychological testing and neuroimaging. Pulsed arterial spin labeling (ASL) magnetic resonance imaging (MRI) was acquired to quantify CBF. Florbetapir positron emission tomography (PET) imaging determined Aß positivity. RESULTS: Adjusting for age, gender, education, and mean cognitive performance, older adults who were Aß+ showed higher cognitive dispersion relative to those who were Aß-. Across the entire sample, higher cognitive dispersion was associated with reduced CBF in inferior parietal and temporal regions. Secondary analyses stratified by Aß status demonstrated that higher cognitive dispersion was associated with reduced CBF among Aß+ individuals but not among those who were Aß-. CONCLUSIONS: Cognitive dispersion may be sensitive to early Aß accumulation and cerebrovascular changes adjusting for demographics and mean neuropsychological performance. Associations between cognitive dispersion and CBF were observed among Aß+ individuals, suggesting that cognitive dispersion may be a marker of brain changes among individuals on the AD continuum. Future studies should examine whether cognitive dispersion predicts brain changes in diverse samples and among those with greater vascular risk burden.