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INTRODUCTION: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia. METHODS: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed‐effect models determined the annual progression of neuropsychological testing. RESULTS: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes. DISCUSSION: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion. Highlights: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion.Attention and executive dysfunction are the strongest predictors of dementia in iRBD.Decline in episodic memory best distinguished dementia‐first from parkinsonism‐first phenoconversion. [ABSTRACT FROM AUTHOR]

Background: Monoaminergic systems are pharmacologically modulable and therefore both a target for symptomatic therapies and a window for the study of disease progression. Although these mechanisms are unclear. We explore the progression and the distribution of monoaminergic deficits in the Alzheimer's Disease (AD) continuum, along with the accumulation of misfolded pathological proteins. Method: We included 50 patients with Alzheimer's Disease (AD) and 42 Healthy Controls (HC). We acquired brain [18F]FDG‐PET images as a marker of neurodegeneration and MMSE as a measure of global cognitive functioning. We performed voxel‐based analysis between AD vs. HC. Using JuSpace toolbox we explored the correlation between [18F]FDG‐PET images and PET maps of dopamine (DAT), serotonin (SERT), noradrenaline (NAT) and choline vesicular (VAChT) transporters cortical distribution. Moreover, we evaluated relative hypometabolism in the main cholinergic nucleus (Meynert nucleus). We divided in two groups the AD patients based on MMSE score (AD Dementia ‐ADD‐ <24; MCI ≥24), to explore the association between monoaminergic disfunction and pathological proteins burden, across the AD continuum. Result: Sample characteristics are provided in Table 1. Results from voxel‐based analysis are shown in Figure 1. In the whole AD group, the distribution of relative cortical hypometabolism was associated with a significant reduction of VAChT availability (p = 0.018). This association remained significant when considering the ADD (p = 0.006), but not the MCI group. Figure 2. β‐amyloid42 levels and β‐amyloid42/40 ratio were inversely correlated with VAChT in the ADD group (p = 0.003; p = 0.038, respectively). No correlation was observed in the MCI group. Lastly, there was no correlation between Meynert nucleus relative hypometabolism and misfolded proteins levels in all groups. Conclusion: In the ADD phase we showed a significant damage in the cortical regions targeted by the cholinergic system. This result was not evident among the other systems studied, nor in the MCI phase. This provides an explanation of the reduction of the cholinesterase inhibitors efficiency in the dementia phase. Moreover, we showed that β‐amyloid accumulation was not associated with Meynert Nucleus degeneration, but that impacted on cholinergic function via damage accumulation in the cortical areas targeted by the cholinergic system. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in the neurophysiological oscillatory mechanisms generating dominant resting‐state eyes closed electroencephalographic (rsEEG) rhythms portray the Alzheimer's disease (AD) continuum, from the preclinical to the dementia stage. Here, we tested whether these abnormalities may be reproducible by analyzing the rsEEG signals acquired in bipolar configuration with a montage consisting of only four centro‐parietal and parieto‐occipital channels (C3‐P3, C4‐P4, P3‐O1, and P4‐O2) in patients with mild cognitive impairment (MCI) due to AD (ADMCI). Method: To evaluate the study hypotheses, clinical, neuropsychological, anthropometric, genetic, cerebrospinal fluid (CSF), MRI, and rsEEG data in 70 Nold and 75 ADMCI subjects from an international archive were used in the present study. The subgroups were matched for age, gender, and education. In all subjects, rsEEG recordings lasted about 3‐5 minutes. The rsEEG data were recorded with a sampling frequency of 128‐512 Hz and related antialiasing bandpass between 0.01 Hz and 60‐100 Hz. Electrode montage included 19 scalp monopolar sensors placed following 10‐20 System. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. Result: Results confirmed previous evidence about the abnormalities of the delta, theta, and alpha rhythms in ADMCI patients compared to Nold subjects. Moreover, as compared to the Nold group, the ADMCI group showed increased delta power density and decreased alpha power density at the C3‐P3, C4‐P4, P3‐O1, and P4‐O2 bipolar channels. Increased theta power density for ADMCI patients was observed only at the C3‐P3 bipolar channel. Best classification accuracy between the ADMCI and Nold individuals reached 81% (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3‐P3 bipolar channel. Conclusion: The current findings provide evidence in the potential use of rsEEG low‐channel portable devices as a topographic biomarker of cognitive decline within the extensive screening of in elderly population at risk of developing AD‐ or other dementia‐related disorders. Moreover, the confirmation of this hypothesis would have exciting applications in the framework of telehealth home monitoring of global brain functions. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that patients with Mild Cognitive Impairment due to Alzheimer's disease (ADMCI) were characterized by reduced posterior rsEEG alpha rhythms after a 12‐month follow‐up (Babiloni et al., 2013). However, none of them have found an alpha deterioration considering a shorter follow‐up. A promising neurophysiological biomarker of the quiet vigilance alteration is the measurement of the posterior rsEEG alpha rhythms reduction in amplitude (reactivity) in the transition from the eyes‐closed to the eyes‐open condition (Babiloni et al., 2022). Here we tested the exploratory hypothesis that ADMCI reactive patients may display a deterioration of rsEEG alpha rhythms at a 6‐month follow‐up as a sign of disease progression (a relevant feature for intervention clinical trials). Method: Clinical, neuroimaging, and rsEEG datasets in 52 ADMCI and 60 matched healthy elderly (Healthy) seniors were available from an international archive (www.pdwaves.eu). The rsEEG frequency bands were individual delta, theta, and alpha (defined based on its posterior topography and "reactivity" to the eyes‐open condition) or background frequency (BGF), as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz). Cortical source estimation was performed by eLORETA freeware. Result: A substantial (> ‐10%) reduction in the posterior alpha source activities during the eyes‐open condition in about 90% and 70% of the Healthy and ADMCI participants, respectively. In the younger ADMCI participants (mean age of 64.3±1.1) with "reactive" rsEEG alpha source activities, posterior alpha source activities during the eyes‐closed condition predicted the global cognitive status at 6‐month follow‐up. In all younger ADMCI participants with "reactive" rsEEG alpha source activities, posterior alpha source activities during the eyes‐closed condition reduced in magnitude at that follow‐up. These effects could not be explained by neuroimaging and neuropsychological biomarkers of AD. Conclusion: These results suggest that in ADMCI patients, the true ("reactive") posterior rsEEG alpha rhythms, when present, predict (in relation to younger age) and are quite sensitive to the effects of the disease progression on neurophysiological mechanisms underpinning vigilance regulation. [ABSTRACT FROM AUTHOR]

Background: Graph theory models a network by its nodes and connections. "Degree" hubs reflect node centrality, while "connector" hubs are those linked to several clusters of nodes. Here we compared hubs modelled from measures of interdependencies of between‐electrode resting‐state eyes‐closed electroencephalography (rsEEG) rhythms in normal old (Nold) and Alzheimer's disease dementia (ADD) participants. As ADD is considered as a "network disease" and is typically associated with abnormal rsEEG delta (< 4 Hz) and alpha rhythms (8‐12 Hz) over associative posterior areas, we predicted abnormal posterior hubs from measures of interdependencies of those rhythms in ADD as compared to Nold participants. Method: To report robust results, we measured interdependencies of rsEEG rhythms from delta to gamma bands (2‐40 Hz) by both bivariate linear lagged connectivity and multivariate (directional) isolated lagged effective coherence. Furthermore, we used three different definitions of "connector" hub. Result: Convergent results showed that in both Nold and ADD groups, there were significant parietal "degree" and "connector" hubs derived from alpha rhythms. These hubs had a prominent outward "directionality" in the two groups, but that "directionality" was lower in ADD than Nold participants (Figure 1). Conclusion: Independent methodologies and hub definitions suggest that ADD patients may be characterized by low outward "directionality" of topologically partially resilient parietal "degree" and "connector" hubs derived from rsEEG alpha rhythms. Combined use of independent methodologies in rsEEG studies may produce robust results in clinical applications in ADD patients. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also by cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients having visual hallucinations. Method: Clinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer's disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched for cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources. Result: As a confirmation of previous studies, compared to the Nold subjects, the AD, LBD, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the LBD and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As novel results, in relation to the LBD and PD patients without visual hallucinations and the control groups (Nold, AD), those with visual hallucinations were characterized by higher parietal delta source activities (LBD, Figure 1) and parieto‐occipital alpha sources activities (PD, Figure 2). Conclusion: These novel results suggest that in LBD and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies in parietal cortex are differently related to visual hallucinations despite the essence of alpha‐synucleinopathy. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients as a function of global cognitive status. Method: Clinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer's disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched as cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources. Result: Compared to the Nold subjects, the AD, DLB, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the DLB and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As main novel results, in relation to the DLB and PD patients with low cognitive deficits and the control groups (Nold, AD), those with high cognitive deficits were characterized by higher parietoccipital delta source activities (DLB, Figure 1) and widespread alpha sources activities (PD, Figure 2). Conclusion: These novel results suggest that in DLB and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies are differently related to cognitive status despite the essence of alpha‐synucleinopathy. [ABSTRACT FROM AUTHOR]

Background: In normal old (Nold) and Alzheimer's disease (AD) persons, a high cognitive reserve makes them more resistant and resilient to brain neuropathology and neurodegeneration. Here we tested whether these effects may affect neurophysiological oscillatory mechanisms generating dominant resting state electroencephalographic (rsEEG) alpha rhythms in Nold and patients with mild cognitive impairment (MCI) due to AD (ADMCI). Method: Data in 60 Nold and 70 ADMCI participants, stratified in higher (Edu+) and lower (Edu‐) educational attainment subgroups, were available in an Italian‐Turkish archive. The subgroups were matched for age, gender, and education. RsEEG cortical sources were estimated by eLORETA freeware. Result: As compared to the Nold‐Edu‐ subgroup, the Nold‐Edu+ subgroup showed greater alpha source activations topographically widespread. On the contrary, in relation to the ADMCI‐Edu‐ subgroup, the ADMCI‐Edu+ subgroup displayed lower alpha source activations topographically widespread (Figure 1). Furthermore, the two ADMCI subgroups had matched cerebrospinal AD diagnostic biomarkers, brain gray‐white matter measures, and neuropsychological scores. Conclusion: The current findings suggest that a high cognitive reserve may be related to changes in rsEEG alpha rhythms in Nold and ADMCI persons. These changes may underlie neuroprotective effects in Nold seniors and subtend functional compensatory mechanisms unrelated to brain structure alterations in ADMCI patients. [ABSTRACT FROM AUTHOR]

Background: Here we tested the hypothesis that gender may diversely affect resting state eyes‐closed electroencephalographic (rsEEG) alpha (8‐12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer's disease and mild cognitive impairment (ADMCI). Method: Clinical and rsEEG datasets in 69 ADMCI and 57 Nold individuals ‐ matched as demography, education, and gender ‐ were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. Each group was stratified into two subgroups based on gender (i.e., female and male). Result: As compared to the Nold female subgroup, the male one showed greater reductions in the rsEEG alpha rhythms topographically widespread. In relation to the ADMCI female subgroup, the male one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions. Notably, the ADMCI subgroups pointed to similar cerebrospinal fluid AD diagnostic biomarkers, gray and white matter brain lesions as revealed by neuroimaging, and clinical and neuropsychological scores. Conclusion: The present results suggest that gender may represent a deranging factor for dominant rsEEG alpha rhythms topographically widespread in Nold seniors and topographically posterior in ADMCI patients. [ABSTRACT FROM AUTHOR]

Background: Cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms are abnormal in patients with amnesic mild cognitive impairment due to Alzheimer's disease (ADMCI). In the present exploratory and retrospective study, we tested whether those abnormalities may be stronger in ADMCI with (ADMCI‐EEA) than without (ADMCI‐noEEA) epileptiform‐like EEG signatures. Method: Clinical, neurophysiological, and rsEEG data in 56 ADMCI patients and 35 normal elderly (Nold) subjects were available in a national archive. The eLORETA freeware estimated rsEEG cortical sources. Area under receiver operating characteristic (AUROC) curves indexed the accuracy of eLORETA solutions in the classification between ADMCI‐EEA and ADMCI‐noEEA individuals. Result: As compared to ADMCI‐noEEA patients, ADMCI‐EEA (N=25%) patients showed worse executive functions (Trail making Test B‐A) and more abnormalities in widespread delta (about 2‐4 Hz) and temporal theta (about 4‐6 Hz) source activities. Furthermore, those sources were able to classify with moderate/good accuracies (AUROC =0.75‐0.85) the ADMCI‐EEA vs. ADMCI‐noEEA individuals. Conclusion: These results suggest higher abnormalities in low‐frequency (i.e. delta and theta) rsEEG cortical activities in ADMCI‐EEA than ADMCI‐noEEA patients at both group and individual levels. [ABSTRACT FROM AUTHOR]