Sex-specific clinical and neurobiological correlates of fatigue in older adults.

Fatigue is a common and distressful symptom in older people and has been associated with adverse health outcomes. Nevertheless, its sex-specific pathophysiological underpinnings and clinical correlates have been scarcely investigated. We aimed to comprehensively explore the clinical and neurobiological determinants of fatigue in cognitively unimpaired older adults. A sex-stratified analysis was conducted to look for differences in the clinical expression of fatigue among women and men. Data on cognitively normal individuals were gathered from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 2 study. Fatigue was defined based on self-report at baseline. For each participant, information on sociodemographics, comorbidities, mood, cognitive performance, frailty, and biomarkers of brain pathology was collected. Logistic regression models, stratified by sex, were conducted to explore the factors associated with fatigue. Among the 291 participants selected, 44 subjects (15.1% of the total sample) self-reported fatigue at baseline. Subjects reporting fatigue were more likely women, had higher frailty degrees, and more severe depressive symptoms than those without fatigue. Moreover, they tended to have lower MRI hippocampus volumes. Among women, those reporting fatigue exhibited higher frailty levels, worse depression, and lower MRI hippocampus volumes relative to those without fatigue. Higher frailty degrees were also observed in men reporting vs. non-reporting fatigue. In the adjusted logistic regression model, more severe depression (OR 1.64, 95% CI 1.18-2.28; p < 0.01) and lower MRI hippocampus volumes (OR 0.41, 95% CI 0.19-0.90; p = 0.03) resulted independently associated with fatigue in women, while higher frailty degrees (OR 3.10, 95% CI 1.27-7.54 per 0.1 increase in a 39-item Frailty index; p = 0.01) in men. Fatigue is a complex symptom with a sex-specific pattern of clinical and neurobiological correlates. A better understanding of the underlying mechanisms of these associations is warranted to develop sex-informed approaches for personalized treatments.

Facial emotion expressivity in patients with Parkinson's and Alzheimer's disease.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders with some overlapping clinical features. Hypomimia (reduced facial expressivity) is a prominent sign of PD and it is also present in AD. However, no study has experimentally assessed hypomimia in AD and compared facial expressivity between PD and AD patients. We compared facial emotion expressivity in patients with PD, AD, and healthy controls (HCs). Twenty-four PD patients, 24 AD patients and 24 HCs were videotaped during neutral facial expressions and while posing six facial emotions (anger, surprise, disgust, fear, happiness, and sadness). Fifteen raters were asked to evaluate the videos using MDS-UPDRS-III (item 3.2) and to identify the corresponding emotion from a seven-forced-choice response format. We measured the percentage of accuracy, the reaction time (RT), and the confidence level (CL) in the perceived accuracy of the raters' responses. We found the highest MDS-UPDRS 3.2 scores in PD, and higher in AD than HCs. When evaluating the posed expression captures, raters identified a lower percentage of correct answers in the PD and AD groups than HCs. There was no difference in raters' response accuracy between the PD and AD. No difference was observed in RT and CL data between groups. Hypomimia in patients correlated positively with the global MDS-UPDRS-III and negatively with Mini Mental State Examination scores. PD and AD patients have a similar pattern of reduced facial emotion expressivity compared to controls. These findings hold potential pathophysiological and clinical implications.

Sundowning in Patients with Dementia: Identification, Prevalence, and Clinical Correlates.

BACKGROUND: The term sundowning is used to describe the emergence or worsening of neuropsychiatric symptoms in late afternoon or early evening in people with dementia. OBJECTIVE: Our aim was to evaluate sundowning's prevalence and clinical manifestations among patients attending a tertiary memory clinic and to investigate its clinical and neuropsychological correlates. METHODS: Patients with dementia attending our memory clinic were enrolled in the study. Sundowning was identified through a specifically designed questionnaire. Sociodemographic and clinical features of sundowners and non-sundowners were compared, and a logistic regression was performed to identify the variables associated with the phenomenon. A subgroup of patients underwent a complete neuropsychological assessment. RESULTS: Among 184 recruited patients, 39 (21.2%) exhibited sundowning, mostly expressed as agitation (56.4%), irritability (53.8%), and anxiety (46.2%). Sundowners were significantly older, had a later dementia onset, exhibited more severe cognitive and functional impairment, more frequent nocturnal awakenings, and hearing loss relative to non-sundowners. They were also more likely to use anticholinergic medications and antipsychotics, and less likely to use memantine. In a multi-adjusted model, the factors significantly associated with sundowning were the Clinical Dementia Rating score (OR 3.88; 95% CI 1.39-10.90) and the use of memantine (OR 0.20; 95% CI 0.05-0.74). Participants with and without sundowning obtained similar results in single domain neuropsychological tests. CONCLUSION: Sundowning is commonly experienced by patients with dementia and appears as a multiply determined condition. Its presence should always be evaluated in clinical practice and a multidimensional approach should be adopted to identify its predictors.

Prevalence and Safety of COVID-19 Vaccination in Community-Dwelling People with Dementia: Findings from a Tertiary Memory Clinic in Italy.

This study aimed to explore the prevalence and safety of SARS-CoV-2 vaccination in individuals with dementia. Patients with mild cognitive impairment or dementia were recruited at a tertiary memory clinic, from March 15 to September 15, 2021. Information on COVID-19 vaccination and adverse events experienced after vaccine administration were collected from caregivers. Two-hundred-seventy subjects were finally recruited. Among them, 253 (93.7%) had received the vaccine and only 69 (27.3%) experienced adverse events. Cognitive and behavioral changes following immunization were only rarely reported. COVID-19 vaccination is safe and well-tolerated in patients with cognitive impairment who should be prioritized in the vaccination campaign.