Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce.

We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6–11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment.

The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215–0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123–0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities.

Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Experimental studies indicate that lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of lithium to treat or prevent dementia.

To determine the benefits of lithium treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease.

A total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25–0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale – cognitive subscale) and functional (Clinical Dementia Rating – Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0–48 months).

Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years. Lithium treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (Aβ1−42) after 36 months.

Long-term lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of lithium in the MCI–Alzheimer's disease continuum.

None.

Verbal fluency (VF) tasks are widely used in neuropsychological evaluations, as a measure of executive/semantic dysfunction. The revised criteria for Alzheimer's disease (AD) diagnosis (National Institute on Aging and the Alzheimer Association, 2011) incorporating biomarkers has increased the interest in finding algorithms that combine neuropsychological and biomarkers features to better predict conversion from mild cognitive impairment (MCI) to AD. Our aim was to compare the most frequently used VF categories to determine which best discriminated cognitively healthy elderly from MCI patients, and whether cerebrospinal fluid (CSF) biomarkers levels (Aβ42, P-tau, T-tau, and Aβ42/P-tau) correlated with patient's performance in MCI.

We studied 37 cognitively healthy elderly and 30 MCI patients in five VF tasks (animal, fruits, means of transportation, FAS-COWA, and verbs); 23 controls and 19 MCI patients had their CSF biomarkers for AD determined.

MCI group performed worse than controls in all VF tasks (p < 0.0001). The cut-off scores were: 14 (animals) (AUC = 0.794), 12 (fruits and means of transportation) (AUC = 0.740 and 0.719, respectively), 41 (FAS) (AUC = 0.744), and 11 (verbs) (AUC = 0.700). The model “animal plus FAS-COWA” was the best to discriminate both groups (AUC = 0.833) (all p < 0.05). MCI produced fewer words than controls in the second-half of the task for all categories (p < 0.001). T-tau levels were negatively correlated to animal fluency (r = −0.485, p = 0.035), and showed a trend for negative correlation with fruits fluency (r = −0.4429, p = 0.057).

Animal fluency alone and combined to FAS-COWA was slightly superior in discriminating controls from MCI (p < 0.001), and correlated to T-tau levels.

The Computer-Administered Neuropsychological Screen for Mild Cognitive Impairment (CANS-MCI) is a computer-based cognitive screening instrument that involves automated administration and scoring and immediate analyses of test sessions. The objective of this study was to translate and culturally adapt the Brazilian Portuguese version of the CANS-MCI (CANS-MCI-BR) and to evaluate its reliability and validity for the diagnostic screening of MCI and dementia due to Alzheimer's disease.

The test was administered to 97 older adults (mean age 73.41 ± 5.27 years) with at least four years of formal education (mean education 12.23 ± 4.48 years). Participants were classified into three diagnostic groups according to global cognitive status (normal controls, n = 41; MCI, n = 35; AD, n = 21) based on clinical data and formal neuropsychological assessments.

The results indicated high internal consistency (Cronbach's α = 0.77) in the total sample. Three-month test-retest reliability correlations were significant and robust (0.875; p < 0.001). A moderate level of concurrent validity was attained relative to the screening test for MCI (MoCA test, r = 0.76, p < 0.001). Confirmatory factor analysis supported the three-factor model of the original test, i.e., memory, language/spatial fluency, and executive function/mental control. Goodness of fit indicators were strong (Bentler Comparative Fit Index = 0.96, Root Mean Square Error of Approximation = 0.09). Receiver operating characteristic curve analyses suggested high sensitivity and specificity (81% and 73% respectively) to screen for possible MCI cases.

The CANS-MCI-BR maintains adequate psychometric characteristics that render it suitable to identify elderly adults with probable cognitive impairment to whom a more extensive evaluation by formal neuropsychological tests may be required.

Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.

To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).

Forty-five participants with aMCI were randomised to receive lithium (0.25–0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ42), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.

Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.

The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.