COVID-19 Isolation Increased Anxiety and Depression in People With Alzheimer Risk

Anxiety and depression have increased both with the COVID-19 pandemic and confinement, notably in women.

Neuroinflammatory biomarkers and amyloid-beta positivity correlated with increased symptoms of anxiety and depression during COVID-19 confinement in individuals, especially women, at risk for Alzheimer disease (AD), according to study findings published in Neurology.

Researchers conducted a retrospective, observational study analyzing whether COVID-19 confinement between May 8 and August 31, 2020 in Spain accelerated AD progression in 921 adults by increasing symptoms of anxiety and depression. These adults were cognitively unimpaired prior to confinement; however, a smaller subset of 254 adults exhibited pre-pandemic AD-related biomarkers. Average length of time between pre-confinement and assessment of confinement totaled 2.4 years.

Pre-pandemic biomarkers included:

  • Amyloid-beta positivity of >12 on the centiloid (CL) scale based on positron emission tomography (PET) or magnetic resonance imaging (MRI) scans
  • MRI-based AD signature related to cortical thickness, especially in the medial temporal lobes which are vulnerable to AD
  • Levels of known neuroinflammatory markers, especially interleukin-6 (IL-6), glial fibrillary acidic protein (GFAP), and triggering receptor expressed on myeloid cells 2 (sTREM2)

The researchers gathered data on sociodemographic factors, including sex, age, and highest education level. Study participants completed monthly online assessments with decreasing percentage of participation from May through August. The Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale (PSS), and the Brief Resilience Scale (BRS) assessed anxiety and depression, and an ad-hoc evaluation assessed caregiving and lifestyle patterns.

Overall, our findings showed a negative impact of COVID-19 confinement on mental health in people at increased risk for AD and support the link between neuropsychiatric symptomatology and brain [amyloid-beta] burden in preclinical AD, notably in women.

According to these assessments, anxiety and depression significantly increased in 16.6% (P <.001) and 9.9% (P <.001) of participants, respectively. Individuals with reduced outdoor exposure (once a week or less) or those without access to open-air environments scored higher on anxiety and depression measures.

Following analysis of the entire cohort, the researchers found that increased anxiety and depression during COVID confinement correlated with amyloid-beta positivity (3.73; 95% CI, 1.1-6.36; P =.006), caregiving (1.37; 95% CI, 0.24-2.5; P =.018), female gender (1.95; 95% CI, 1.1-2.79; P <.001), younger age (-0.12; 95% CI, -0.18 to -0.052; P <.001), and lower education level (-0.16; 95% CI, -0.28 to -0.042; P =.008).

After analyzing the subgroup with available pre-pandemic biomarker data, lower IL-6 levels in the cerebrospinal fluid correlated with higher HADS scores.

The researchers speculated that heightened anxiety and depression related to COVID-19 isolation increased the stress response and dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in increased amyloid-beta plaque deposition.

“Overall, our findings showed a negative impact of COVID-19 confinement on mental health in people at increased risk for AD and support the link between neuropsychiatric symptomatology and brain [amyloid-beta] burden in preclinical AD, notably in women,” the researchers noted.

They added “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.”

Study limitations included the exclusion of participants with missing data lowering effect power, the exclusive focus on individuals at-risk for AD, the lack of a control group, and the inability to discern cause and effect. Results may be related to confinement, but also might be attributable to a general reaction to the pandemic itself.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Akinci M, Peña-Gómez C, Operto G, et al. Pre-pandemic Alzheimer disease biomarkers and anxious-depressive symptoms during the COVID-19 confinement in cognitively unimpaired adults. Neurology. Published online August 2, 2022. doi:10.1212/WNL.0000000000200948