%0 Journal Article %J J Alzheimers Dis %D 2022 %T Cognitive Decline Risk Stratification in People with Late-Onset Epilepsy of Unknown Etiology: An Electroencephalographic Connectivity and Graph Theory Pilot Study. %A Costa, Cinzia %A Vecchio, Fabrizio %A Romoli, Michele %A Miraglia, Francesca %A Nardi Cesarini, Elena %A Alù, Francesca %A Calabresi, Paolo %A Rossini, Paolo Maria %K Aged %K Cognitive Dysfunction %K Dementia %K Electroencephalography %K Epilepsy %K Female %K Humans %K Male %K Neuropsychological Tests %K Pilot Projects %K Risk Assessment %X

BACKGROUND: Although people with late onset epilepsy of unknown etiology (LOEU) are at higher risk of cognitive decline compared to the general population, we still lack affordable tools to predict and stratify their risk of dementia.

OBJECTIVE: This pilot-study investigates the potential application of electroencephalography (EEG) network small-world (SW) properties in predicting cognitive decline among patients with LOEU.

METHODS: People diagnosed with LOEU and normal cognitive examination at the time of epilepsy diagnosis were included. Cerebrospinal fluid biomarkers, brain imaging, and neuropsychological assessment were performed at the time of epilepsy diagnosis. Baseline EEG was analyzed for SW properties. Patients were followed-up over time with neuropsychological testing to define the trajectory of cognitive decline.

RESULTS: Over 5.1 years of follow-up, among 24 patients diagnosed with LOEU, 62.5% were female, mean age was 65.3 years, thirteen developed mild cognitive impairment (MCI), and four developed dementia. Patients with LOEU developing MCI had lower values of SW coefficients in the delta (p = 0.03) band and higher SW values in the alpha frequency bands (p = 0.02) compared to patients having normal cognition at last follow-up. The two separate ANOVAs, for low and alpha bands, confirmed an interaction between SW and cognitive decline at follow-up. A similar gradient was confirmed for patients developing dementia compared to those with normal cognitive function as well as to those developing MCI.

CONCLUSION: Baseline EEG analysis through SW is worth investigating as an affordable, widely available tool to stratify LOEU patients for their risk of cognitive decline.

%B J Alzheimers Dis %V 88 %P 893-901 %8 2022 %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/34842184?dopt=Abstract %R 10.3233/JAD-210350 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Learning Processes and Brain Connectivity in A Cognitive-Motor Task in Neurodegeneration: Evidence from EEG Network Analysis. %A Vecchio, Fabrizio %A Miraglia, Francesca %A Quaranta, Davide %A Lacidogna, Giordano %A Marra, Camillo %A Rossini, Paolo Maria %X

Electroencephalographic (EEG) rhythms are linked to any kind of learning and cognitive performance including motor tasks. The brain is a complex network consisting of spatially distributed networks dedicated to different functions including cognitive domains where dynamic interactions of several brain areas play a pivotal role. Brain connectome could be a useful approach not only to mechanisms underlying brain cognitive functions, but also to those supporting different mental states. This goal was approached via a learning task providing the possibility to predict performance and learning along physiological and pathological brain aging. Eighty-six subjects (22 healthy, 47 amnesic mild cognitive impairment, 17 Alzheimer's disease) were recruited reflecting the whole spectrum of normal and abnormal brain connectivity scenarios. EEG recordings were performed at rest, with closed eyes, both before and after the task (Sensory Motor Learning task consisting of a visual rotation paradigm). Brain network properties were described by Small World index (SW), representing a combination of segregation and integration properties. Correlation analyses showed that alpha 2 SW in pre-task significantly predict learning (r  =  -0.2592, p < 0.0342): lower alpha 2 SW (higher possibility to increase during task and better the learning of this task), higher the learning as measured by the number of reached targets. These results suggest that, by means of an innovative analysis applied to a low-cost and widely available techniques (SW applied to EEG), the functional connectome approach as well as conventional biomarkers would be effective methods for monitoring learning progress during training both in normal and abnormal conditions.

%B J Alzheimers Dis %V 66 %P 471-481 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/30282357?dopt=Abstract %R 10.3233/JAD-180342 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Predicting and Tracking Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease: Structural Brain Biomarkers. %A Marizzoni, Moira %A Ferrari, Clarissa %A Jovicich, Jorge %A Albani, Diego %A Babiloni, Claudio %A Cavaliere, Libera %A Didic, Mira %A Forloni, Gianluigi %A Galluzzi, Samantha %A Hoffmann, Karl-Titus %A Molinuevo, José Luis %A Nobili, Flavio %A Parnetti, Lucilla %A Payoux, Pierre %A Ribaldi, Federica %A Rossini, Paolo Maria %A Schönknecht, Peter %A Soricelli, Andrea %A Hensch, Tilman %A Tsolaki, Magda %A Visser, Pieter Jelle %A Wiltfang, Jens %A Richardson, Jill C %A Bordet, Régis %A Blin, Olivier %A Frisoni, Giovanni B %X

BACKGROUND: Early Alzheimer's disease (AD) detection using cerebrospinal fluid (CSF) biomarkers has been recommended as enrichment strategy for trials involving mild cognitive impairment (MCI) patients.

OBJECTIVE: To model a prodromal AD trial for identifying MRI structural biomarkers to improve subject selection and to be used as surrogate outcomes of disease progression.

METHODS: APOE ɛ4 specific CSF Aβ42/P-tau cut-offs were used to identify MCI with prodromal AD (Aβ42/P-tau positive) in the WP5-PharmaCog (E-ADNI) cohort. Linear mixed models were performed 1) with baseline structural biomarker, time, and biomarker×time interaction as factors to predict longitudinal changes in ADAS-cog13, 2) with Aβ42/P-tau status, time, and Aβ42/P-tau status×time interaction as factors to explain the longitudinal changes in MRI measures, and 3) to compute sample size estimation for a trial implemented with the selected biomarkers.

RESULTS: Only baseline lateral ventricle volume was able to identify a subgroup of prodromal AD patients who declined faster (interaction, p = 0.003). Lateral ventricle volume and medial temporal lobe measures were the biomarkers most sensitive to disease progression (interaction, p≤0.042). Enrichment through ventricular volume reduced the sample size that a clinical trial would require from 13 to 76%, depending on structural outcome variable. The biomarker needing the lowest sample size was the hippocampal subfield GC-ML-DG (granule cells of molecular layer of the dentate gyrus) (n = 82 per arm to demonstrate a 20% atrophy reduction).

CONCLUSION: MRI structural biomarkers can enrich prodromal AD with fast progressors and significantly decrease group size in clinical trials of disease modifying drugs.

%B J Alzheimers Dis %8 2018 Jun 09 %G eng %R 10.3233/JAD-180152 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Association Between Serum Ceruloplasmin Specific Activity and Risk of Alzheimer's Disease. %A Siotto, Mariacristina %A Simonelli, Ilaria %A Pasqualetti, Patrizio %A Mariani, Stefania %A Caprara, Deborah %A Bucossi, Serena %A Ventriglia, Mariacarla %A Molinario, Rossana %A Antenucci, Mirca %A Rongioletti, Mauro %A Rossini, Paolo Maria %A Squitti, Rosanna %K Aged %K Alzheimer Disease %K Apolipoprotein E4 %K Area Under Curve %K Biomarkers %K Blood Chemical Analysis %K Ceruloplasmin %K Copper %K Female %K Genotype %K Genotyping Techniques %K Humans %K Logistic Models %K Male %K Multivariate Analysis %K Prognosis %K Risk %K ROC Curve %K Sensitivity and Specificity %K Transferrin %X

Meta-analyses demonstrate copper involvement in Alzheimer's disease (AD), and the systemic ceruloplasmin status in relation to copper is an emerging issue. To deepen this matter, we evaluated levels of ceruloplasmin concentration, ceruloplasmin activity, ceruloplasmin specific activity (eCp/iCp), copper, non-ceruloplasmin copper iron, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype in a sample of 84 AD patients and 58 healthy volunteers. From the univariate logistic analyses we found that ceruloplasmin concentration, eCp/iCp, copper, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype were significantly associated with the probability of AD. In the multivariable logistic regression analysis, we selected the best subset of biological predictors by the forward stepwise procedure. The analysis showed a decrease of the risk of having AD for eCp/iCp (p = 0.001) and an increase of this risk for non-ceruloplasmin copper (p = 0.008), age (p = 0.001), and APOE-ɛ4 allele (p <  0.001). The estimated model showed a good power in discriminating AD patients from healthy controls (area under curve: 88% ; sensitivity: 66% ; specificity 93%). These data strength the breakdown of copper homeostasis and propose eCp/iCp as a reliable marker of ceruloplasmin status.

%B J Alzheimers Dis %V 50 %P 1181-9 %8 2016 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836154?dopt=Abstract %R 10.3233/JAD-150611