Association of years to parent's sporadic onset and risk factors with neural integrity and Alzheimer biomarkers

Arenaza‐Urquijo, Eider M.; Salvadó, Gemma; Operto, Grégory; Minguillón, Carolina; Sánchez‐Benavides, Gonzalo; Crous‐Bou, Marta; Grau‐Rivera, Oriol; Sala‐Vila, Aleix; Falcón, Carles; Suárez‐Calvet, Marc; Zetterberg, Henrik; Blennow, Kaj; Gispert, Juan Domingo; Molinuevo, José Luís

doi:10.1212/wnl.0000000000010527

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…It is important to note those studies that do not find sex differences, cross-sectionally [97], or longitudinally [68]. Although some studies report sex differences in Aβ-PET [98,99], and proximity to parental age at onset in sporadic AD may influence Aβ-PET signal in females [100], findings are not reported consistently perhaps due to differences in age between these cohorts [101]. As such, the literature suggests age and APOEε4 status are risk factors for elevated signal in PET markers of both Aβ and tau, with sex showing divergent patterns.…”

Section: Aβ and Tau-pet Signal Associations With Demographicsmentioning

confidence: 99%

Recent Advances in Imaging of Preclinical, Sporadic, and Autosomal Dominant Alzheimer's Disease

Buckley

2021

Neurotherapeutics

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Observing Alzheimer's disease (AD) pathological changes in vivo with neuroimaging provides invaluable opportunities to understand and predict the course of disease. Neuroimaging AD biomarkers also allow for real-time tracking of diseasemodifying treatment in clinical trials. With recent neuroimaging advances, along with the burgeoning availability of longitudinal neuroimaging data and big-data harmonization approaches, a more comprehensive evaluation of the disease has shed light on the topographical staging and temporal sequencing of the disease. Multimodal imaging approaches have also promoted the development of data-driven models of AD-associated pathological propagation of tau proteinopathies. Studies of autosomal dominant, early sporadic, and late sporadic courses of the disease have shed unique insights into the AD pathological cascade, particularly with regard to genetic vulnerabilities and the identification of potential drug targets. Further, neuroimaging markers of b-amyloid, tau, and neurodegeneration have provided a powerful tool for validation of novel fluid cerebrospinal and plasma markers. This review highlights some of the latest advances in the field of human neuroimaging in AD across these topics, particularly with respect to positron emission tomography and structural and functional magnetic resonance imaging.

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Section: Aβ and Tau-pet Signal Associations With Demographicsmentioning

confidence: 99%

Recent Advances in Imaging of Preclinical, Sporadic, and Autosomal Dominant Alzheimer's Disease

Buckley

2021

Neurotherapeutics

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“…Herein, we focused on CU adults with a subgroup experiencing SCD, many of them being first-order descendants of sporadic AD patients and thus at a higher risk of developing cognitive decline and AD dementia [ 37 , 38 ]. Our main aim was to investigate whether the intensity of SCD was associated with greater anxious/depressive symptoms during the COVID-19 confinement independent of pre-confinement anxiety/depression levels.…”

Section: Introductionmentioning

confidence: 99%

Subjective cognitive decline and anxious/depressive symptoms during the COVID-19 pandemic: what is the role of stress perception, stress resilience, and β-amyloid?

et al. 2022

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Background The COVID-19 pandemic may worsen the mental health of people reporting subjective cognitive decline (SCD) and therefore their clinical prognosis. We aimed to investigate the association between the intensity of SCD and anxious/depressive symptoms during confinement and the underlying mechanisms. Methods Two hundred fifty cognitively unimpaired participants completed the Hospital Anxiety and Depression Scale (HADS) and SCD-Questionnaire (SCD-Q) and underwent amyloid-β positron emission tomography imaging with [18F] flutemetamol (N = 205) on average 2.4 (± 0.8) years before the COVID-19 confinement. During the confinement, participants completed the HADS, Perceived Stress Scale (PSS), Brief Resilience Scale (BRS), and an ad hoc questionnaire on worries (access to primary products, self-protection materials, economic situation) and lifestyle changes (sleep duration, sleep quality, eating habits). We investigated stress-related measurements, worries, and lifestyle changes in relation to SCD. We then conducted an analysis of covariance to investigate the association of SCD-Q with HADS scores during the confinement while controlling for pre-confinement anxiety/depression scores and demographics. Furthermore, we introduced amyloid-β positivity, PSS, and BRS in the models and performed mediation analyses to explore the mechanisms explaining the association between SCD and anxiety/depression. Results In the whole sample, the average SCD-Q score was 4.1 (± 4.4); 70 (28%) participants were classified as SCD, and 26 (12.7%) were amyloid-β-positive. During the confinement, participants reporting SCD showed higher PSS (p = 0.035) but not BRS scores (p = 0.65) than those that did not report SCD. No differences in worries or lifestyle changes were observed. Higher SCD-Q scores showed an association with greater anxiety/depression scores irrespective of pre-confinement anxiety/depression levels (p = 0.002). This association was not significant after introducing amyloid-β positivity and stress-related variables in the model (p = 0.069). Amyloid-β positivity and PSS were associated with greater HADS irrespective of pre-confinement anxiety/depression scores (p = 0.023; p < 0.001). The association of SCD-Q with HADS was mediated by PSS (p = 0.01). Conclusions Higher intensity of SCD, amyloid-β positivity, and stress perception showed independent associations with anxious/depressive symptoms during the COVID-19 confinement irrespective of pre-confinement anxiety/depression levels. The association of SCD intensity with anxiety/depression was mediated by stress perception, suggesting stress regulation as a potential intervention to reduce affective symptomatology in the SCD population in the face of stressors.

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“…Older adults with FH of sporadic AD are at a higher risk for cognitive impairment and dementia 20 and start showing AD-related pathologic changes early during midlife. 21 , 22 We investigated the associations of Aβ burden, neuroinflammation, and brain structure data acquired approximately 2.4 years before the pandemic with anxious-depressive symptomatology during the COVID-19 confinement. We hypothesized that (1) adults with Aβ burden, higher CSF IL-6 values, and/or lower structural integrity in AD-related regions (medial temporal lobe structures) will show greater anxiety-depression during the confinement and (2) these associations will be independent of the preconfinement anxiety-depression levels.…”

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Prepandemic Alzheimer Disease Biomarkers and Anxious-Depressive Symptoms During the COVID-19 Confinement in Cognitively Unimpaired Adults

et al. 2022

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Background and ObjectivesIncreased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer’s disease (AD), which may accelerate disease progression. We investigated whether amyloid-β, cortical thickness in medial temporal lobe structures, neuroinflammation and sociodemographic factors were associated with greater anxious-depressive symptoms during the COVID-19 confinement.MethodsThis retrospective observational study included cognitively unimpaired older adults from the ALFA (Alzheimer and FAmilies) cohort, the majority with a family history of sporadic AD. Participants performed the Hospital Anxiety and Depression Scale (HADS) during the COVID-19 confinement. A subset had available retrospective (on average: 2.4 years before) HADS assessment, amyloid [18F] flutemetamol PET and structural MRI scans and CSF markers of neuroinflammation (interleukin-6 [IL-6], triggering receptor expressed on myeloid cells 2 and glial fibrillary acidic protein levels). We performed multivariable linear regression models to investigate the associations of pre-pandemic AD-related biomarkers and sociodemographic factors with HADS scores during the confinement. We further performed an analysis of covariance in order to adjust by participants’ pre-pandemic anxiety-depression levels. Finally, we explored the role of stress and lifestyle changes (sleep patterns, eating, drinking, smoking habits, and medication use) on the tested associations and performed sex-stratified analyses.ResultsWe included 921 (254 with AD biomarkers) participants. Amyloid-β positivity (B=3.73; 95%CI=1.1 to 6.36; p=.006), caregiving (B=1.37; 95%CI=0.24 to 2.5; p=.018), sex (women: B=1.95; 95%CI=1.1 to 2.79; p<.001), younger age (B=-0.12; 95%CI=-0.18 to -0.052; p<.001) and lower education (B=-0.16; 95%CI=-0.28 to -0.042; p=.008) were associated with greater anxious-depressive symptoms during the confinement. Considering pre-pandemic anxiety-depression levels, we further observed an association between lower levels of CSF IL-6 (B=-5.11; 95%CI=-10.1 to -0.13; p=.044) and greater HADS scores. The results were independent of stress-related variables and lifestyle changes. Stratified analysis revealed that the associations were mainly driven by women.DiscussionOur results link AD-related pathophysiology and neuroinflammation with greater anxious-depressive symptomatology during the COVID-19-related confinement, notably in women. AD pathophysiology may increase neuropsychiatric symptomatology in response to stressors. This association may imply a worse clinical prognosis in people at risk for AD after the pandemic, and thus deserves to be considered by clinicians.Trial Registration InformationClinicalTrials.gov Identifier NCT02485730

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Association of years to parent's sporadic onset and risk factors with neural integrity and Alzheimer biomarkers

Cited by 4 publications

References 31 publications

Recent Advances in Imaging of Preclinical, Sporadic, and Autosomal Dominant Alzheimer's Disease

Recent Advances in Imaging of Preclinical, Sporadic, and Autosomal Dominant Alzheimer's Disease

Subjective cognitive decline and anxious/depressive symptoms during the COVID-19 pandemic: what is the role of stress perception, stress resilience, and β-amyloid?

Prepandemic Alzheimer Disease Biomarkers and Anxious-Depressive Symptoms During the COVID-19 Confinement in Cognitively Unimpaired Adults

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