Franco Giubilei’s research while affiliated with Sapienza University of Rome and other places

Patients with mild cognitive impairment due to Alzheimer’s disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8–12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid–tau biomarkers in ADMCI patients. An international database provided clinical–demographic–rsEEG datasets for cognitively unimpaired older (Healthy; N = 45), ADMCI (N = 70), and noADMCI (N = 45) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. Posterior rsEEG alpha source activities were reduced in the ADMCI group compared not only to the Healthy group but also to the noADMCI group (p < 0.001). Negative associations between the CSF phospho-tau and total tau levels and posterior rsEEG alpha source activities were observed in the ADMCI group (p < 0.001), whereas those with CSF amyloid beta 42 levels were marginal. These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through rsEEG alpha rhythms are mainly affected by brain tauopathy in ADMCI patients.

The Italian telephone-based Mini-Mental State Examination (Itel-MMSE) is considered a very easy tool for screening individuals with dementia, gained importance during COVID-19, but lacks validation and faces a ceiling effect. In the present study, we conducted a study standardizing and validating it, establishing cut-off values for two versions. Across 24 Italian sites, 707 healthy individuals (50–89 years, men: 268, women: 439) with diverse educational levels (3–24 years) were recruited. Subjects met criteria for normal conditions investigated through a semi-structured interview covering neurological, psychiatric, general medical, and psychopharmacological history. Two test versions were created to assess test–retest reliability at 45-day intervals. We also enrolled 187 subjects with Mild Cognitive Impairment (MCI) and 181 with Alzheimer's Disease (AD) for validation. The raw scores obtained on both versions of Itel-MMSE were set as dependent variables in linear regression models that included age, education, and gender as independent variables. Mean raw Itel-MMSE1 score was 20.82 (range: 13–22). Multiple linear regression demonstrated significant effects of sociodemographic variables for age and education, establishing a new cut-off ≥ 18.49. Mean raw Itel-MMSE2 score was 20.97 (range: 10–22), with a new cut-off ≥ 18.45. Validation showed high informative values, with areas under the curve (AUCs) for MCI and AD conditions and both versions (Itel-MMSE1: MCI AUC = 0.801, AD AUC = 0.907; Itel-MMSE2: MCI AUC = 0.827, AD AUC = 0.977). The Itel-MMSE proves valuable as a screening method for detecting and monitoring dementia in remote phone screenings, with different cut-offs aiding MCI patient identification in clinical settings.

The present study was developed based on the data of The PDWAVES Consortium (www.pdwaves.eu) and the PharmaCog project. The Partners and institutional affiliations are reported on the cover page of this manuscript. In this study, the clinical, neuropsychological, and magnetic resonance imaging data collection and analysis in patients with ADMCI and healthy control participants were partially supported by the funds of “Ricerca Corrente 2022-2023” (Italian Ministry of Health) to the IRCCS Synlab SDN of Naples (Italy), IRCCS Ospedale San Martino of Genoa (Italy), Oasi Research Institute-IRCCS, Troina (Italy), IRCCS Fatebenefratelli of Brescia (Italy), and IRCCS San Raffaele Pisana of Rome (Italy). Prof. Claudio Del Percio’s and Dr. Roberta Biundo’s work for this study was supported by funds of the “PRIN-2022” project entitled "AmyEEG” (Italian Ministry of University and Research, Prot. 2022FJAXY8). At the same time, Prof. Claudio Babiloni’s work was supported by funds of the “Horizon Marie S. Curie Doctoral Network ” project entitled "CombiDiag” (European Committee, Proposal: 101071485).

Here we tested the hypothesis of a relationship between the cortical default mode network (DMN) structural integrity and the resting-state electroencephalographic (rsEEG) rhythms in patients with Alzheimer’s disease with dementia (ADD). Clinical and instrumental datasets in 45 ADD patients and 40 normal elderly (Nold) persons originated from the PDWAVES Consortium (www.pdwaves.eu). Individual rsEEG delta, theta, alpha, and fixed beta and gamma bands were considered. Freeware platforms served to derive (1) the (gray matter) volume of the DMN, dorsal attention (DAN), and sensorimotor (SMN) cortical networks and (2) the rsEEG cortical eLORETA source activities. We found a significant positive association between the DMN gray matter volume, the rsEEG alpha source activity estimated in the posterior DMN nodes (parietal and posterior cingulate cortex), and the global cognitive status in the Nold and ADD participants. Compared with the Nold, the ADD group showed lower DMN gray matter, lower rsEEG alpha source activity in those nodes, and lower global cognitive status. This effect was not observed in the DAN and SMN. These results suggest that the DMN structural integrity and the rsEEG alpha source activities in the DMN posterior hubs may be related and predict the global cognitive status in ADD and Nold persons.

Background: Alzheimer disease (AD) is a neurodegenerative disorder characterized by ß-amyloid accumulation in the brain. A simple and reliable biomarker for AD that is not invasive is urgently needed, particularly in the preclinical and early stages of the disease. The retina shares with the brain, the same embryologic origins and it is affected by similar vascular changes. The aim of this study was to analyze the characteristics of the retinal and choriocapillaris vascular structure through optical coherence tomography-angiography (OCTA) evaluation in patients with early AD. Methods: Eighteen patients with early AD (study group) and 18 healthy age-matched subjects (control group) were enrolled in the study. All patients underwent full neurologic and ophthalmologic examination, and OCTA scans. Results: We found a significant reduction in flow area of choriocapillaris in the study group compared with the control group (P-value: 0.006), suggesting an impairment of choriocapillaris circulation in patients with early AD. Conclusion: OCTA provides accumulative evidence on the microvasculature changes of the retina and choriocapillaris in patients with AD. Further studies and improved OCTA software are necessary to better evaluate the role of vascular changes shown with OCTA as potential biomarkers in early disease.