| Cross-sectional case-control studies  

Pre-pandemic Alzheimer Disease biomarkers and anxious-depressive symptoms during the COVID-19 confinement in cognitively unimpaired adults

Increased anxious-depressive symptomatology is observed in the preclinical stage of Alzheimer’s disease (AD), which may accelerate disease progression. In this article the authors 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.

This 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). Multivariable linear regression models were performed to investigate the associations of pre-pandemic AD-related biomarkers and sociodemographic factors with HADS scores during the confinement. An analysis of covariance was also performed in order to adjust by participants’ pre-pandemic anxiety-depression levels. Finally, the authors 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. 921 (254 with AD biomarkers) participants were included. 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, the authors 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. The authors concluded underlying that their 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.
Akinci M, Peña-Gómez C, Operto G, Fuentes-Julian S, Deulofeu C, Sánchez-Benavides G, Milà-Alomà M, Grau-Rivera O, Gramunt N, Navarro A, Minguillón C, Fauria K, Suridjan I, Kollmorgen G, Bayfield A, Blennow K, Zetterberg H, Molinuevo JL, Suárez-Calvet M, Gispert JD, Arenaza-Urquijo EM. Pre-pandemic Alzheimer Disease Biomarkers and Anxious-Depressive Symptoms During the COVID-19 Confinement in Cognitively Unimpaired Adults. Neurology. 2022 Aug 2:10.1212/WNL.0000000000200948.

doi: 10.1212/WNL.0000000000200948