RESUMO
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.
RESUMO
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.
Assuntos
Doença de Alzheimer , Negro ou Afro-Americano , Hispânico ou Latino , Idoso , Humanos , Biomarcadores , Cognição , FenótipoRESUMO
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.
Assuntos
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
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.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Neuroimagem , Encéfalo/patologia , Tomografia por Emissão de Pósitrons , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , CogniçãoRESUMO
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.
Assuntos
Disfunção Cognitiva , Exercício Físico , Humanos , Idoso , Exercício Físico/fisiologia , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Acelerometria/métodosRESUMO
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.
Assuntos
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.
RESUMO
Posttraumatic stress disorder (PTSD) treatment has been associated with improvement in quality of life (QOL); however, little is known about factors that moderate treatment-related changes in QOL, particularly cognitive factors. Executive functioning (EF) is important for success across all aspects of everyday life and predicts better psychological and physical health. EF is important to QOL, but more work is needed to better understand the association between EF and QOL improvements following interventions. We hypothesized that poorer baseline EF would be associated with less improvement in overall life satisfaction and satisfaction with health following PTSD treatment. U.S. veterans who served after the September 11, 2001 terrorist attacks (post 9-11; N = 80) with PTSD and a history of mild-to-moderate traumatic brain injury were randomized to standard cognitive processing therapy (CPT) or CPT combined with cognitive rehabilitation (SMART-CPT). Multilevel modeling was used to examine whether baseline EF performance was associated with changes in QOL scores from pretreatment to follow-up across both groups. Results indicated that poorer baseline performance on EF tests of working memory and inhibition were associated with less treatment-related improvements in general life satisfaction and satisfaction with health, rs = .26-.36. Treatment condition did not moderate any results. Future research should examine whether implementing EF-focused techniques before and/or concurrently with CPT for individuals with poorer baseline working memory and inhibition enhances QOL treatment gains, particularly in terms of general life and health-related satisfaction.
Assuntos
Lesões Encefálicas Traumáticas , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Qualidade de Vida/psicologia , Veteranos/psicologia , Lesões Encefálicas Traumáticas/complicações , Função Executiva/fisiologiaRESUMO
INTRODUCTION: Neurofilament light (NFL) reflects neuroaxonal damage and is implicated in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known about NFL in pre-MCI stages, such as in individuals with objectively-defined subtle cognitive decline (Obj-SCD). METHODS: Two hundred ninety-four participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent baseline blood draw and serial neuropsychological testing over 5 years of follow-up. RESULTS: Individuals with Obj-SCD and MCI showed elevated baseline plasma NFL relative to the cognitively normal (CN) group. Across the sample, elevated NFL predicted faster rate of cognitive and functional decline. Within the Obj-SCD and MCI groups, higher NFL levels predicted faster rate of decline in memory and preclinical AD composite score compared to the CN group. DISCUSSION: Findings demonstrate the utility of plasma NFL as a biomarker of early AD-related changes, and provide support for the use of Obj-SCD criteria in clinical research to better capture subtle cognitive changes.
Assuntos
Doença de Alzheimer/sangue , Disfunção Cognitiva/sangue , Estado Funcional , Proteínas de Neurofilamentos/sangue , Testes Neuropsicológicos/estatística & dados numéricos , Idoso , Biomarcadores/sangue , Feminino , Humanos , MasculinoRESUMO
INTRODUCTION: Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition. METHODS: For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (Aß) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aß, including interactions with APOE ε4-carrier status. RESULTS: Adjusting for tau PET, Aß was not associated with cognition and did not interact with APOE. In contrast, adjusting for Aß PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in ε4-carriers, even among Aß-negative individuals. DISCUSSION: Findings suggest that APOE may interact with tau independently of Aß and that elevated MTL tau confers negative cognitive consequences in Aß-negative ε4 carriers.
Assuntos
Peptídeos beta-Amiloides/genética , Apolipoproteínas E/metabolismo , Transtornos da Memória/diagnóstico por imagem , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/sangue , Apolipoproteínas E/genética , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Cognição , Demência/genética , Demência/psicologia , Feminino , Heterozigoto , Humanos , Masculino , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/metabolismo , Proteínas tau/genéticaRESUMO
OBJECTIVE: To develop and validate the Discrepancy-based Evidence for Loss of Thinking Abilities (DELTA) score. The DELTA score characterizes the strength of evidence for cognitive decline on a continuous spectrum using well-established psychometric principles for improving detection of cognitive changes. METHODS: DELTA score development used neuropsychological test scores from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (two tests each from Memory, Executive Function, and Language domains). We derived regression-based normative reference scores using age, gender, years of education, and word-reading ability from robust cognitively normal ADNI participants. Discrepancies between predicted and observed scores were used for calculating the DELTA score (range 0-15). We validated DELTA scores primarily against longitudinal Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Functional Activities Questionnaire (FAQ) scores (baseline assessment through Year 3) using linear mixed models and secondarily against cross-sectional Alzheimer's biomarkers. RESULTS: There were 1359 ADNI participants with calculable baseline DELTA scores (age 73.7 ± 7.1 years, 55.4% female, 100% white/Caucasian). Higher baseline DELTA scores (stronger evidence of cognitive decline) predicted higher baseline CDR-SOB (ΔR2 = .318) and faster rates of CDR-SOB increase over time (ΔR2 = .209). Longitudinal changes in DELTA scores tracked closely and in the same direction as CDR-SOB scores (fixed and random effects of mean + mean-centered DELTA, ΔR2 > .7). Results were similar for FAQ scores. High DELTA scores predicted higher PET-Aß SUVr (ρ = 324), higher CSF-pTau/CSF-Aß ratio (ρ = .460), and demonstrated PPV > .9 for positive Alzheimer's disease biomarker classification. CONCLUSIONS: Data support initial development and validation of the DELTA score through its associations with longitudinal functional changes and Alzheimer's biomarkers. We provide several considerations for future research and include an automated scoring program for clinical use.
Assuntos
Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos/normas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Biomarcadores , Cognição , Estudos de Coortes , Estudos Transversais , Função Executiva , Feminino , Humanos , Masculino , PsicometriaRESUMO
OBJECTIVE: Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance. METHOD: Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass). RESULTS: Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition. CONCLUSION: Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.
Assuntos
Lesões Encefálicas Traumáticas/reabilitação , Terapia Cognitivo-Comportamental , Disfunção Cognitiva/reabilitação , Remediação Cognitiva , Depressão/reabilitação , Simulação de Doença/reabilitação , Desempenho Psicomotor , Transtornos de Estresse Pós-Traumáticos/reabilitação , Adulto , Concussão Encefálica/complicações , Concussão Encefálica/fisiopatologia , Concussão Encefálica/psicologia , Concussão Encefálica/reabilitação , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/psicologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Depressão/etiologia , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Simulação de Doença/etiologia , Simulação de Doença/fisiopatologia , Simulação de Doença/psicologia , Avaliação de Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Síndrome Pós-Concussão/fisiopatologia , Síndrome Pós-Concussão/psicologia , Síndrome Pós-Concussão/reabilitação , Desempenho Psicomotor/fisiologia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto JovemRESUMO
OBJECTIVE: The current study examined the interactive effect of type 2 diabetes and Alzheimer disease (AD) risk factors on the rate of functional decline in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative. METHODS: Participants underwent annual assessments that included the Functional Activities Questionnaire, an informant-rated measure of everyday functioning. Multilevel modeling, controlling for demographic variables and ischemic risk, examined the interactive effects of diabetes status (diabetes, n=69; no diabetes, n=744) and AD risk factors in the prediction of 5-year longitudinal change in everyday functioning. One model was run for each AD risk factor, including: objectively-defined subtle cognitive decline (Obj-SCD), and genetic susceptibility [apolipoprotein E ε4 (APOE ε4) as well as cerebrospinal fluid ß-amyloid (Aß), total tau (tau), and hyperphosphorylated tau (p-tau). RESULTS: The 3-way diabetes×AD risk factor×time interaction predicted increased rates of functional decline in models that examined Obj-SCD, APOE ε4, tau, and p-tau positivity, but not Aß positivity. CONCLUSIONS: Participants with both diabetes and at least 1 AD risk factor (ie, Obj-SCD, APOE ε4, tau, and p-tau positivity) demonstrated faster functional decline compared with those without both risk factors (diabetes or AD). These findings have implications for early identification of, and perhaps earlier intervention for, diabetic individuals at risk for future functional difficulty.
Assuntos
Atividades Cotidianas , Disfunção Cognitiva , Diabetes Mellitus Tipo 2/complicações , Voluntários Saudáveis , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Proteínas tau/líquido cefalorraquidianoRESUMO
OBJECTIVE: To better concurrently address emotional and neuropsychological symptoms common in veterans with comorbid post-traumatic stress disorder (PTSD) and history of traumatic brain injury (TBI), we integrated components of compensatory cognitive training from the Cognitive Symptom Management and Rehabilitation Therapy (CogSMART) programme into cognitive processing therapy (CPT) for PTSD to create a hybrid treatment, SMART-CPT (CogSMART+CPT). This study compared the efficacy of standard CPT with SMART-CPT for treatment of veterans with comorbid PTSD and history of TBI reporting cognitive symptoms. METHODS: One hundred veterans with PTSD, a history of mild to moderate TBI and current cognitive complaints were randomised and received individually delivered CPT or SMART-CPT for 12 weeks. Participants underwent psychological, neurobehavioural and neuropsychological assessments at baseline, on completion of treatment and 3 months after treatment. RESULTS: Both CPT and SMART-CPT resulted in clinically significant reductions in PTSD and postconcussive symptomatology and improvements in quality of life. SMART-CPT resulted in additional improvements in the neuropsychological domains of attention/working memory, verbal learning/memory and novel problem solving. CONCLUSION: SMART-CPT, a mental health intervention for PTSD, combined with compensatory cognitive training strategies, reduces PTSD and neurobehavioural symptoms and also provides added value by improving cognitive functioning.
Assuntos
Lesões Encefálicas Traumáticas/psicologia , Transtornos Cognitivos/terapia , Terapia Cognitivo-Comportamental/métodos , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/psicologia , Adulto , Lesões Encefálicas Traumáticas/terapia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida , Avaliação de Sintomas , Resultado do TratamentoRESUMO
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) separates "early" and "late" mild cognitive impairment (MCI) based on a single memory test. We compared ADNI's MCI classifications to our neuropsychological approach, which more broadly assesses cognitive abilities. METHODS: Three hundred thirty-six ADNI-2 participants were classified as "early" or "late" MCI. Cluster analysis was performed on neuropsychological test data, and participants were reclassified based on cluster results. These two staging approaches were compared on progression rates, cerebrospinal fluid biomarkers, and cortical thickness profiles. RESULTS: There was little correspondence between the two staging methods. ADNI's early MCI group included a large proportion of false-positive diagnostic errors. The reclassified neuropsychological MCI groups showed steeper survival curves and more abnormal biomarkers. CONCLUSIONS: Our novel neuropsychological approach improved the staging of MCI by (1) capturing individuals at an early symptomatic stage, (2) minimizing false-positive cases, and (3) identifying a late MCI group further along the disease trajectory.
Assuntos
Biomarcadores , Disfunção Cognitiva/diagnóstico , Erros de Diagnóstico/prevenção & controle , Testes Neuropsicológicos/estatística & dados numéricos , Idoso , Biomarcadores/líquido cefalorraquidiano , Análise por Conglomerados , Progressão da Doença , Feminino , Humanos , Masculino , NeuroimagemRESUMO
INTRODUCTION: The low mild cognitive impairment (MCI) to cognitively normal (CN) reversion rate in the Alzheimer's Disease Neuroimaging Initiative (2-3%) suggests the need to examine reversion by other means. We applied comprehensive neuropsychological criteria (NP criteria) to determine the resulting MCI to CN reversion rate. METHODS: Participants with CN (n = 641) or MCI (n = 569) were classified at baseline and year 1 using NP criteria. Demographic, neuropsychological, and Alzheimer's disease biomarker variables as well as progression to dementia were examined across stable CN, reversion, and stable MCI groups. RESULTS: NP criteria produced a one-year reversion rate of 15.8%. Reverters had demographics, Alzheimer's disease biomarkers, and risk-of-progression most similar to the stable CN group and showed the most improvement on neuropsychological measures from baseline to year 1. DISCUSSION: NP criteria produced a reversion rate that is consistent with, albeit modestly improved from, reversion rates in meta-analyses. Reverters' biomarker profiles and progression rates suggest that NP criteria accurately tracked with underlying pathophysiologic status.
Assuntos
Cognição/fisiologia , Disfunção Cognitiva , Neuroimagem , Testes Neuropsicológicos/estatística & dados numéricos , Idoso , Biomarcadores , Encéfalo/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Demografia , Feminino , HumanosRESUMO
INTRODUCTION: We examined reasons for low mild cognitive impairment (MCI)-to-cognitively normal (CN) reversion rates in the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: CN and MCI participants were identified as remaining stable, progressing, or reverting at 1-year of follow-up (Year 1). Application of ADNI's MCI criteria at Year 1 in addition to Alzheimer's disease biomarkers by group were examined. RESULTS: The MCI-to-CN reversion rate was 3.0%. When specific components were examined, 22.5% of stable MCI participants had normal memory performance at Year 1 and their Alzheimer's disease biomarkers were consistent with the stable CN group. At Year 1, when all MCI criteria were not met, the more subjective Clinical Dementia Rating rather than objective memory measure appeared to drive continuation of the MCI diagnosis. DISCUSSION: Results demonstrate an artificially low 1-year MCI-to-CN reversion rate in ADNI-diagnosed participants. If the Logical Memory cutoffs had been consistently applied, the reversion rate would have been at least 21.8%.
Assuntos
Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Neuroimagem , Testes Neuropsicológicos , Idoso , Biomarcadores/líquido cefalorraquidiano , Encéfalo , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos/normas , Testes Neuropsicológicos/estatística & dados numéricos , Estados Unidos , Proteínas tau/líquido cefalorraquidianoRESUMO
BACKGROUND/AIMS: Mild cognitive impairment (MCI) lacks a "gold standard" operational definition. The Jak/Bondi actuarial neuropsychological criteria for MCI are associated with improved diagnostic stability and prediction of progression to dementia compared to conventional MCI diagnostic approaches, although its utility in diagnosing MCI in old-old individuals (age 75+) is unknown. Therefore, we investigated the applicability of neuropsychological MCI criteria among old-old from the Framingham Heart Study. METHODS: A total of 347 adults (ages 79-102) were classified as cognitively normal or MCI via Jak/Bondi and conventional Petersen/Winblad criteria, which differ on cutoffs for cognitive impairment and number of impaired scores required for a diagnosis. Cox models examined MCI status in predicting risk of progression to dementia. RESULTS: MCI diagnosed by both the Jak/Bondi and Petersen/Winblad criteria was associated with incident dementia; however, when both criteria were included in the regression model together, only the Jak/Bondi criteria remained statistically significant. At follow-up, the Jak/Bondi criteria had a lower MCI-to-normal reversion rate than the Petersen/Winblad criteria. CONCLUSIONS: Our findings are consistent with previous research on the Jak/Bondi criteria and support the use of a comprehensive neuropsychological diagnostic approach for MCI among old-old individuals.
Assuntos
Envelhecimento/psicologia , Disfunção Cognitiva , Demência , Testes Neuropsicológicos/normas , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Demência/diagnóstico , Demência/psicologia , Progressão da Doença , Feminino , Avaliação Geriátrica/métodos , Humanos , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: Although subjective cognitive complaints (SCC) are an integral component of the diagnostic criteria for mild cognitive impairment (MCI), previous findings indicate they may not accurately reflect cognitive ability. Within the Alzheimer's Disease Neuroimaging Initiative, we investigated longitudinal change in the discrepancy between self- and informant-reported SCC across empirically derived subtypes of MCI and normal control (NC) participants. METHODS: Data were obtained for 353 MCI participants and 122 "robust" NC participants. Participants were classified into three subtypes at baseline via cluster analysis: amnestic MCI, mixed MCI, and cluster-derived normal (CDN), a presumptive false-positive group who performed within normal limits on neuropsychological testing. SCC at baseline and two annual follow-up visits were assessed via the Everyday Cognition Questionnaire (ECog), and discrepancy scores between self- and informant-report were calculated. Analysis of change was conducted using analysis of covariance. RESULTS: The amnestic and mixed MCI subtypes demonstrated increasing ECog discrepancy scores over time. This was driven by an increase in informant-reported SCC, which corresponded to participants' objective cognitive decline, despite stable self-reported SCC. Increasing unawareness was associated with cerebrospinal fluid Alzheimer's disease biomarker positivity and progression to Alzheimer's disease. In contrast, CDN and NC groups over-reported cognitive difficulty and demonstrated normal cognition at all time points. CONCLUSIONS: MCI participants' discrepancy scores indicate progressive underappreciation of their evolving cognitive deficits. Consistent over-reporting in the CDN and NC groups despite normal objective cognition suggests that self-reported SCC do not predict impending cognitive decline. Results demonstrate that self-reported SCC become increasingly misleading as objective cognitive impairment becomes more pronounced. (JINS, 2018, 24, 842-853).
Assuntos
Cognição , Disfunção Cognitiva/psicologia , Autorrelato , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/psicologia , Conscientização , Análise por Conglomerados , Disfunção Cognitiva/líquido cefalorraquidiano , Progressão da Doença , Função Executiva , Reações Falso-Positivas , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , AutoimagemRESUMO
OBJECTIVES: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. METHODS: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. RESULTS: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. CONCLUSIONS: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104-112).