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Introduction: Mental health conditions are associated with cognition and physical function in older adults. We examined whether worry and ruminative brooding, key symptoms of certain mental health conditions, are related to subjective and/or objective measures of cognitive and physical (cardiovascular) health. Methods: We used baseline data from 282 participants from the SCD-Well and Age-Well trials (178 female; agemean = 71.1 years). We measured worry and ruminative brooding using the Penn State Worry Questionnaire and the Ruminative Response Scale-brooding subscale. We assessed subjective physical health using the WHOQOL-Bref physical subscale, and objective physical health via blood pressure and modified versions of the Framingham Risk Score and Charlson Comorbidity Index. With subjective and objective cognition, we utilized the Cognitive Difficulties Scale and a global composite (modified Preclinical Alzheimer's Cognitive Composite, PACC5, with the Wechsler Adult Intelligence Scale-IV, category fluency, Mattis Dementia Rating Scale-2, and either the California Verbal Learning Test or the Rey Auditory Verbal Learning Test). We conducted linear regressions, adjusted for education, age, sex and cohort. Results: Worry and ruminative brooding were negatively associated with subjective physical health (worry: ß = -0.245, 95%CI -0.357 to -0.133, p < 0.001; ruminative brooding: ß = -0.224, 95%CI -0.334 to -0.113, p < 0.001) and subjective cognitive difficulties (worry: ß = 0.196, 95%CI 0.091 to 0.302, p < 0.001; ruminative brooding: ß = 0.239, 95%CI 0.133 to 0.346, p < 0.001). We did not observe associations between worry or ruminative brooding and any measure of objective health. Discussion: Worry and ruminative brooding may be common mechanisms associated with subjective but not objective health. Alternatively, cognitively unimpaired older adults may become aware of subtle changes not captured by objective measures used in this study. Interventions reducing worry and ruminative brooding may promote subjective physical and cognitive health; however, more research is needed to determine causality of the relationships.
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Aging is associated with cognitive changes, even in the absence of brain pathology. This study aimed to determine if meditation training, by comparison to active and passive control groups, is linked to changes in the perception of cognitive functioning in older adults. One hundred thirty-four healthy older participants from the Age-Well Randomized Clinical Trial were included: 45 followed a meditation training, 45 a non-native language training and 44 had no intervention. Subjective cognition was assessed at baseline and following the 18-month intervention period. Perception of attentional efficiency was assessed using internal and external Attentional Style Questionnaire (ASQ) subscale scores. Perception of global cognitive capacities was measured via the total score of Cognitive Difficulties Scale (CDS). Deltas ([posttest minus pretest scores]/standard deviation at pretest) were calculated for the analyses. Generalized mixed effects models controlling for age, sex, education and baseline scores revealed that meditation training decreased the vulnerability score toward external distractors measured by the ASQ compared to non-native language training. However, no between-groups differences on ASQ internal or CDS total scores were observed. Results suggest a beneficial effect of meditation practice on perceived management of external distracting information in daily life. Meditation training may cultivate the ability to focus on specific information (e.g., breath) and ignore stimulation from other kinds of stimuli (e.g., noise).
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The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.
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Disseminação de Informação , Neuroimagem , Humanos , Disseminação de Informação/métodos , Neuroimagem/métodos , Encéfalo/diagnóstico por imagemRESUMO
OBJECTIVE: Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. METHODS: Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid ß1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract. RESULTS: AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. INTERPRETATION: Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.
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Doença de Alzheimer , Doenças de Pequenos Vasos Cerebrais , Imagem de Tensor de Difusão , Substância Branca , Humanos , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Feminino , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/patologia , Masculino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Idoso , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/metabolismo , Estudos ProspectivosRESUMO
INTRODUCTION: Older adults experiencing subjective cognitive decline (SCD) have a higher risk of dementia. Reducing this risk through behavioral interventions, which can increase emotional well-being (mindfulness and compassion) and physical activity, is crucial in SCD. METHODS: SCD-Well is a multicenter, observer-blind, randomized, controlled, superiority trial. Three hundred forty-seven participants (mean [standard deviation] age: 72.7 [6.9] years; 64.6% women) were recruited from memory clinics in four European sites to assess the impact of an 8-week caring mindfulness-based approach for seniors (CMBAS) and a health self-management program (HSMP) on mindfulness, self-compassion, and physical activity. RESULTS: CMBAS showed a significant within-group increase in self-compassion from baseline to post-intervention and both a within- and between-group increase to follow-up visit (24 weeks). HSMP showed a significant within- and between-group increase in physical activity from baseline to post-intervention and to follow-up visit. DISCUSSION: Non-pharmacological interventions can differentially promote modifiable factors linked to healthy aging in older adults with SCD.
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Objective: Poor sleep and high levels of repetitive negative thinking (RNT), including future-directed (ie, worry) and past-directed (ie, brooding) negative thoughts, have been associated with markers of dementia risk. The relationship between RNT and sleep health in older adults is unknown. This study aimed to investigate this association and its specificities including multiple dimensions of objective and subjective sleep. Methods: This study used a cross sectional quantitative design with baseline data from 127 cognitively healthy older adults (mean age 69.4 ± 3.8 years; 63% female) who took part in the Age-Well clinical trial, France. RNT (ie, worry and brooding) levels were measured using the Penn State Worry Questionnaire and the Rumination Response Scale (brooding subscale). Polysomnography was used to assess sleep objectively, and the Pittsburgh Sleep Quality Index and the St. Mary's Hospital Sleep Questionnaire were used to measure sleep subjectively. In primary analyses the associations between RNT and sleep (ie, objective sleep duration, fragmentation and efficiency and subjective sleep disturbance) were assessed via adjusted regressions. Results: Higher levels of RNT were associated with poorer objective sleep efficiency (worry: ß=-0.32, p<0.001; brooding: ß=-0.26, p=0.002), but not objective sleep duration, fragmentation, or subjective sleep disturbance. Additional analyses, however, revealed differences in levels of worry between those with short, compared with typical and long objective sleep durations (p < 0.05). Conclusion: In cognitively healthy older adults, RNT was associated with sleep characteristics that have been implicated in increased dementia risk. It will take additional research to ascertain the causal link between RNT and sleep characteristics and how they ultimately relate to the risk of developing dementia.
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STUDY OBJECTIVES: In aging, reduced delta power (0.5-4 Hz) during N2 and N3 sleep has been associated with gray matter (GM) atrophy and hypometabolism within frontal regions. Some studies have also reported associations between N2 and N3 sleep delta power in specific sub-bands and amyloid pathology. Our objective was to better understand the relationships between spectral power in delta sub-bands during N2-N3 sleep and brain integrity using multimodal neuroimaging. METHODS: In-home polysomnography was performed in 127 cognitively unimpaired older adults (mean ageâ ±â SD: 69.0â ±â 3.8 years). N2-N3 sleep EEG power was calculated in delta (0.5-4 Hz), slow delta (0.5-1 Hz), and fast delta (1-4 Hz) frequency bands. Participants also underwent magnetic resonance imaging and Florbetapir-PET (early and late acquisitions) scans to assess GM volume, brain perfusion, and amyloid burden. Amyloid accumulation over ~21 months was also quantified. RESULTS: Higher delta power was associated with higher GM volume mainly in fronto-cingular regions. Specifically, slow delta power was positively correlated with GM volume and perfusion in these regions, while the inverse association was observed with fast delta power. Delta power was neither associated with amyloid burden at baseline nor its accumulation over time, whatever the frequency band considered. CONCLUSIONS: Our results show that slow delta is particularly associated with preserved brain structure, and highlight the importance of analyzing delta power sub-bands to better understand the associations between delta power and brain integrity. Further longitudinal investigations with long follow-ups are needed to disentangle the associations among sleep, amyloid pathology, and dementia risk in older populations. CLINICAL TRIAL INFORMATION: Name: Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training (Age-Well). URL: https://clinicaltrials.gov/ct2/show/NCT02977819?term=Age-Well&draw=2&rank=1. See STROBE_statement_AGEWELL in supplemental materials. REGISTRATION: EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.
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Sono de Ondas Lentas , Idoso , Humanos , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Neuroimagem , Polissonografia , Sono , Fases do SonoRESUMO
OBJECTIVES: As the world population is ageing, it is vital to understand how older adults can maintain and deepen their psychological well-being as they are confronted with the unique challenges of ageing in a complex world. Theoretical work has highlighted the promising role of intentional mental training such as meditation practice for enhancing human flourishing. However, meditation-based randomised controlled trials in older adults are lacking. We aimed to investigate the effects of meditation training on psychological well-being in older adults. METHODS: This study presents a secondary analysis of the Age-Well trial (ClinicalTrials.gov: NCT02977819), which randomised 137 healthy older adults (age range: 65 to 84 years) to an 18-month meditation training, an active comparator (English language training), or a passive control. Well-being was measured at baseline, mid-intervention, and 18-month post-randomisation using the Psychological Well-being Scale (PWBS), the World Health Organisation's Quality of Life (QoL) Assessment psychological subscale, and composite scores reflecting the meditation-based well-being dimensions of awareness, connection, insight, and a global score comprising the average of these meditation-based dimensions. RESULTS: The 18-month meditation training was superior to English training on changes in the global score (0.54 [95% CI: 0.26, 0.82], p = 0.0002) and the subscales of awareness, connection, insight, and superior to no-intervention only on changes in the global score (0.54 [95% CI: 0.26, 0.82], p = 0.0002) and awareness. Between-group differences in psychological QoL in favour of meditation did not remain significant after adjusting for multiple comparisons. There were no between-group differences in PWBS total score. Within the meditation group, psychological QoL, awareness, insight, and the global score increased significantly from baseline to 18-month post-randomisation. CONCLUSION: The longest randomised meditation training conducted to date enhanced a global composite score reflecting the meditation-based well-being dimensions of awareness, connection, and insight in older adults. Future research is needed to delineate the cognitive, affective, and behavioural factors that predict responsiveness to meditation and thus help refine the development of tailored meditation training.
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Meditação , Humanos , Idoso , Idoso de 80 Anos ou mais , Meditação/métodos , Qualidade de Vida , Bem-Estar Psicológico , Envelhecimento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: Older adults with subjective cognitive decline (SCD) recruited from memory clinics have an increased risk of developing dementia and regularly experience reduced psychological well-being related to memory concerns and fear of dementia. Research on improving well-being in SCD is limited and lacks non-pharmacological approaches. We investigated whether mindfulness-based and health education interventions can enhance well-being in SCD. METHODS: The SCD-Well trial (ClinicalTrials.gov: NCT03005652) randomised 147 older adults with SCD to an 8-week caring mindfulness-based approach for seniors (CMBAS) or an active comparator (health self-management programme [HSMP]). Well-being was assessed at baseline, post-intervention, and 6-month post-randomisation using the Psychological Well-being Scale (PWBS), the World Health Organisation's Quality of Life (QoL) Assessment psychological subscale, and composites capturing meditation-based well-being dimensions of awareness, connection, and insight. Mixed effects models were used to assess between- and within-group differences in change. RESULTS: CMBAS was superior to HSMP on changes in connection at post-intervention. Within both groups, PWBS total scores, psychological QoL, and composite scores did not increase. Exploratory analyses indicated increases in PWBS autonomy at post-intervention in both groups. CONCLUSION: Two non-pharmacological interventions were associated with only limited effects on psychological well-being in SCD. Longer intervention studies with waitlist/retest control groups are needed to assess if our findings reflect intervention brevity and/or minimal base rate changes in well-being.
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Disfunção Cognitiva , Demência , Atenção Plena , Autogestão , Humanos , Idoso , Atenção Plena/métodos , Qualidade de Vida , Bem-Estar Psicológico , Disfunção Cognitiva/terapiaRESUMO
Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances might have greater behavioral consequences. Polysomnography and neuropsychological assessments were performed in 135 cognitively intact older adults (mean age ± SD: 69.4 ± 3.8y) from the Age-Well randomized controlled trial (baseline data). Two measures of cognitive engagement throughout life were used as CR proxies. Linear regression analyses were performed between the proportion of SWS, and executive function and episodic memory composite scores. Then, interaction analyses between SWS and CR proxies on cognition were conducted to assess the possible impact of CR on these links. SWS was positively associated with episodic memory, but not with executive function. CR proxies modulated the associations between SWS and both executive and episodic memory performance. Specifically, individuals with higher CR were able to maintain cognitive performance despite low amounts of SWS. This study provides the first evidence that CR may protect against the deleterious effects of age-related sleep changes on cognition.
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Reserva Cognitiva , Sono de Ondas Lentas , Idoso , Humanos , Cognição , Vida Independente , Testes Neuropsicológicos , SonoRESUMO
Importance: Nonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. Objective: To investigate the effects of 18 months' meditation training and 18 months' non-native language training on cognition in older adults. Design, Setting, and Participants: This study was a secondary analysis of the Age-Well trial, an 18-month, observer-masked, randomized clinical trial with 3 parallel arms. Eligible participants were community-dwelling adults aged 65 years and older residing in Caen, France. Participants were enrolled from November 24, 2016, to March 5, 2018, and randomly assigned (1:1:1) to meditation training, non-native language (English) training, or no intervention arms. Final follow-up was completed on February 6, 2020. Data were analyzed between December 2021 and November 2022. Interventions: The 18-month meditation and non-native language training interventions were structurally equivalent and included 2-hour weekly group sessions, daily home practice of 20 minutes or longer, and 1 day of more intensive home practice. The no intervention group was instructed not to change their habits and to continue living as usual. Main Outcomes and Measures: Cognition (a prespecified secondary outcome of the Age-Well trial) was assessed preintervention and postintervention via the Preclinical Alzheimer Cognitive Composite 5 (PACC5), and composites assessing episodic memory, executive function, and attention. Results: Among 137 randomized participants, 2 were excluded for not meeting eligibility criteria, leaving 135 (mean [SD] age, 69.3 [3.8] years; 83 female [61%]) eligible for analysis. One participant among the remaining 135 did not complete the trial. In adjusted mixed effects models, no interaction effects were observed between visit and group for PACC5 (F2,131.39 = 2.58; P = .08), episodic memory (F2,131.60 = 2.34; P = .10), executive function (F2,131.26 = 0.89; P = .41), or attention (F2,131.20 = 0.34; P = .79). Results remained substantively unchanged across sensitivity and exploratory analyses. Conclusions and Relevance: In this secondary analysis of an 18-month randomized trial, meditation and non-native language training did not confer salutary cognitive effects. Although further analyses are needed to explore the effects of these interventions on other relevant outcomes related to aging and well-being, these findings did not support the use of these interventions for enhancing cognition in cognitively healthy older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT02977819.
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Meditação , Memória Episódica , Humanos , Feminino , Idoso , Meditação/métodos , Terapia da Linguagem , Cognição , Função ExecutivaRESUMO
OBJECTIVE: Self-perceived cognitive functioning, considered highly relevant in the context of aging and dementia, is assessed in numerous ways-hindering the comparison of findings across studies and settings. Therefore, the present study aimed to link item-level self-report questionnaire data from international aging studies. METHOD: We harmonized secondary data from 24 studies and 40 different questionnaires with item response theory (IRT) techniques using a graded response model with a Bayesian estimator. We compared item information curves to identify items with high measurement precision at different levels of the self-perceived cognitive functioning latent trait. Data from 53,030 neuropsychologically intact older adults were included, from 13 English language and 11 non-English (or mixed) language studies. RESULTS: We successfully linked all questionnaires and demonstrated that a single-factor structure was reasonable for the latent trait. Items that made the greatest contribution to measurement precision (i.e., "top items") assessed general and specific memory problems and aspects of executive functioning, attention, language, calculation, and visuospatial skills. These top items originated from distinct questionnaires and varied in format, range, time frames, response options, and whether they captured ability and/or change. CONCLUSIONS: This was the first study to calibrate self-perceived cognitive functioning data of geographically diverse older adults. The resulting item scores are on the same metric, facilitating joint or pooled analyses across international studies. Results may lead to the development of new self-perceived cognitive functioning questionnaires guided by psychometric properties, content, and other important features of items in our item bank. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Cognição , Disfunção Cognitiva , Humanos , Idoso , Teorema de Bayes , Disfunção Cognitiva/diagnóstico , Inquéritos e Questionários , Autorrelato , PsicometriaRESUMO
Background: Alzheimer's disease (AD) and Korsakoff's syndrome (KS) are two major neurocognitive disorders characterized by amnesia but AD is degenerative while KS is not. The objective is to compare regional volume deficits within the Papez circuit in AD and KS, considering AD progression. Methods: 18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on global cognitive deficits with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted. Results: For the cingulate gyri, and anterior thalamic nuclei, all patient groups were affected compared to controls but did not differ between each other. Smaller volumes were observed in all patient groups compared to controls in the mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS than AD. MTT volumes were damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD. Conclusions: There are commonalities in the pattern of volume deficits in KS and AD within the Papez circuit with the anterior thalamic nuclei, cingulate cortex and hippocampus (in MAD only) being damaged to the same extent. The specificity of KS relies on the alteration of the MTT and the severity of the MB shrinkage. Further comparative studies including other imaging modalities and a neuropsychological assessment are required.
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Amyloid-ß accumulation starts in highly connected brain regions and is associated with functional connectivity alterations in the early stages of Alzheimer's disease. This regional vulnerability is related to the high neuronal activity and strong fluctuations typical of these regions. Recently, dynamic functional connectivity was introduced to investigate changes in functional network organization over time. High dynamic functional connectivity variations indicate increased regional flexibility to participate in multiple subnetworks, promoting functional integration. Currently, only a limited number of studies have explored the temporal dynamics of functional connectivity in the pre-dementia stages of Alzheimer's disease. We study the associations between abnormal cerebrospinal fluid amyloid and both static and dynamic properties of functional hubs, using eigenvector centrality, and their relationship with cognitive performance, in 701 non-demented participants from the European Prevention of Alzheimer's Dementia cohort. Voxel-wise eigenvector centrality was computed for the whole functional magnetic resonance imaging time series (static), and within a sliding window (dynamic). Differences in static eigenvector centrality between amyloid positive (A+) and negative (A-) participants and amyloid-tau groups were found in a general linear model. Dynamic eigenvector centrality standard deviation and range were compared between groups within clusters of significant static eigenvector centrality differences, and within 10 canonical resting-state networks. The effect of the interaction between amyloid status and cognitive performance on dynamic eigenvector centrality variability was also evaluated with linear models. Models were corrected for age, sex, and education level. Lower static centrality was found in A+ participants in posterior brain areas including a parietal and an occipital cluster; higher static centrality was found in a medio-frontal cluster. Lower eigenvector centrality variability (standard deviation) occurred in A+ participants in the frontal cluster. The default mode network and the dorsal visual networks of A+ participants had lower dynamic eigenvector centrality variability. Centrality variability in the default mode network and dorsal visual networks were associated with cognitive performance in the A- and A+ groups, with lower variability being observed in A+ participants with good cognitive scores. Our results support the role and timing of eigenvector centrality alterations in very early stages of Alzheimer's disease and show that centrality variability over time adds relevant information on the dynamic patterns that cause static eigenvector centrality alterations. We propose that dynamic eigenvector centrality is an early biomarker of the interplay between early Alzheimer's disease pathology and cognitive decline.
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BACKGROUND AND OBJECTIVES: Sleep disordered breathing (SDB) has been related to amyloid deposition and an increased dementia risk. However, how SDB relates to medial temporal lobe neurodegeneration and subsequent episodic memory impairment is unclear. Our objective was to investigate the impact of amyloid positivity on the associations between SDB severity, medial temporal lobe subregions, and episodic memory performance in cognitively unimpaired older adults. METHODS: Data were acquired between 2016 and 2020 in the context of the Age-Well randomized controlled trial of the Medit-Aging European project. Participants older than 65 years who were free of neurologic, psychiatric, or chronic medical diseases were recruited from the community. They completed a neuropsychological evaluation, in-home polysomnography, a Florbetapir PET, and an MRI, including a specific high-resolution assessment of the medial temporal lobe and hippocampal subfields. Multiple linear regressions were conducted to test interactions between amyloid status and SDB severity on the volume of MTL subregions, controlling for age, sex, education, and the ApoE4 status. Secondary analyses aimed at investigating the links between SDB, MTL subregional atrophy, and episodic memory performance at baseline and at a mean follow-up of 20.66 months in the whole cohort and in subgroups stratified according to amyloid status. RESULTS: We included 122 cognitively intact community-dwelling older adults (mean age ± SD: 69.40 ± 3.85 years, 77 women, 26 Aß+ individuals) in baseline analyses and 111 at follow-up. The apnea-hypopnea index interacted with entorhinal (ß = -0.81, p < 0.001, pη2 = 0.19), whole hippocampal (ß = -0.61, p < 0.001, pη2 = 0.10), subiculum (ß = -0.56, p = 0.002, pη2 = 0.08), CA1 (ß = -0.55, p = 0.002, pη2 = 0.08), and DG (ß = -0.53, p = 0.003, pη2 = 0.08) volumes such that a higher sleep apnea severity was related to lower MTL subregion volumes in amyloid-positive individuals, but not in those who were amyloid negative. In the whole cohort, lower whole hippocampal (r = 0.27, p = 0.005) and CA1 (r = 0.28, p = 0.003) volumes at baseline were associated with worse episodic memory performance at follow-up. DISCUSSION: Overall, we showed that SDB was associated with MTL atrophy in cognitively asymptomatic older adults engaged in the Alzheimer continuum, which may increase the risk of developing memory impairment over time. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02977819.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Feminino , Idoso , Lobo Temporal/metabolismo , Acrilatos , Amiloide/metabolismo , Imageamento por Ressonância Magnética , Proteínas Amiloidogênicas , Atrofia , Tomografia por Emissão de Pósitrons , Peptídeos beta-Amiloides/metabolismoRESUMO
White matter hyperintensities (WMH), frequently seen in older adults, are usually considered vascular lesions, and participate in the vascular contribution to cognitive impairment and dementia. However, emerging evidence highlights the heterogeneity of WMH pathophysiology, suggesting that non-vascular mechanisms could also be involved, notably in Alzheimer's disease (AD). This led to the alternative hypothesis that in AD, part of WMH may be secondary to AD-related processes. The current perspective brings together the arguments from different fields of research, including neuropathology, neuroimaging and fluid biomarkers, and genetics, in favor of this alternative hypothesis. Possible underlying mechanisms leading to AD-related WMH, such as AD-related neurodegeneration or neuroinflammation, are discussed, as well as implications for diagnostic criteria and management of AD. We finally discuss ways to test this hypothesis and remaining challenges. Acknowledging the heterogeneity of WMH and the existence of AD-related WMH may improve personalized diagnosis and care of patients.
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Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Doença de Alzheimer/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/patologia , NeuroimagemRESUMO
BACKGROUND AND OBJECTIVES: Studies are sparse regarding the association between the informant-reported subjective memory decline (informant report) and Alzheimer disease (AD) biomarkers. This study thus aimed at determining the clinical relevance of the informant report throughout the AD clinical continuum, by assessing its specific relationships with amyloid deposition, cognition, and neurodegeneration. METHODS: Participants from the Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce (IMAP+) primary cohort and the Alzheimer Disease Neuroimaging Initiative (ADNI) replication cohort were included; all underwent multimodal neuroimaging and neuropsychological assessments. Follow-up data of IMAP+ participants over up to 36 months were also used for longitudinal analyses. The informant report was measured with the Cognitive Difficulties Scale (IMAP+) and Everyday Cognition (ADNI). General linear models were used to assess the cross-sectional associations between the informant report and amyloid-PET, cognitive performances, and neurodegeneration (atrophy and hypometabolism) in Alzheimer signature areas; while longitudinal links were assessed in IMAP+ with linear mixed-effects models. RESULTS: A total of 110 IMAP+ participants were included, including 32 cognitively unimpaired older individuals (controls, age: 70.91 ± 6.57 years, female: 50%), 25 patients with subjective cognitive decline (SCD, 65.88 ± 6.64, 40%), 35 with mild cognitive impairment (MCI, 72.49 ± 7.5, 34%), and 18 with Alzheimer-type dementia (AD dementia, 68.17 ± 8.59, 28%). Seven hundred thirty-one ADNI participants were included, including 157 controls (74.21 ± 5.95, 55%), 84 with SCD (72.00 ± 5.41, 63%), 369 with MCI (71.84 ± 7.4, 44%), and 121 with AD dementia (74.29 ± 7.75, 40%). In IMAP+, a higher informant report strongly correlated to greater amyloid-PET, specifically in patients with MCI (ß = 0.48, p = 0.003), and to lower cognitive performance in patients with SCD (global cognition, ß = -0.41, p = 0.04) and MCI (memory, ß = -0.37, p = 0.03). Findings in patients with MCI were replicated in the ADNI (amyloid-PET, ß = 0.25, p < 0.001; memory, ß = -0.22, p < 0.001) and extended to neurodegeneration in AD signature areas (ß = -0.2, p < 0.001). Longitudinal analyses in IMAP+ showed links with global cognitive decline over time in patients with MCI (estimate -0.74, SE 0.26, p = 0.005) and SCD (estimate -0.36, SE 0.26, p = 0.02) where a higher baseline informant report also predicted an increased amyloid-PET over time (estimate 0.008, SE 0.003, p = 0.02). DISCUSSION: Altogether, our findings suggest that the informant report is particularly relevant in patients with MCI where it strongly relates to higher amyloid-PET, indicative of impairment due to AD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01638949.
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Doença de Alzheimer , Disfunção Cognitiva , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Doença de Alzheimer/psicologia , Amiloide , Peptídeos beta-Amiloides/metabolismo , Biomarcadores , Encéfalo/metabolismo , Cognição , Disfunção Cognitiva/psicologia , Estudos Transversais , Transtornos da Memória , Tomografia por Emissão de PósitronsRESUMO
Medial temporal lobe (MTL) subregions are differentially affected in Alzheimer's disease (AD), with a specific involvement of the entorhinal cortex (ERC), perirhinal cortex and hippocampal cornu ammonis (CA)1. While amyloid (Aß) and APOEε4 are respectively the first molecular change and the main genetic risk factor in AD, their links with MTL atrophy remain relatively unclear. Our aim was to uncover these effects using baseline data from 130 participants included in the Age-Well study, for whom ultra-high-resolution structural MRI, amyloid-PET and APOEε4 genotype were available. No volume differences were observed between Aß + (n = 24) and Aß- (n = 103), nor between APOE4+ (n = 35) and APOE4- (n = 95) participants. However, our analyses showed that both Aß and APOEε4 status interacted with age on CA1, which is known to be specifically atrophied in early AD. In addition, APOEε4 status moderated the effects of age on other subregions (subiculum, ERC), suggesting a more important contribution of APOEε4 than Aß to MTL atrophy in cognitively unimpaired population. These results are crucial to develop MRI-based biomarkers to detect early AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Idoso , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Atrofia/patologia , Genótipo , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons , Proteínas tau/metabolismo , Lobo Temporal/metabolismoRESUMO
Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-ß, more advanced stages (AT) of AD pathology and APOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury.