Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 281
1.
Neurobiol Aging ; 137: 62-77, 2024 May.
Article En | MEDLINE | ID: mdl-38431999

Resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms are dominant in posterior cortical areas in healthy adults and are abnormal in subjective memory complaint (SMC) persons with Alzheimer's disease amyloidosis. This exploratory study in 161 SMC participants tested the relationships between those rhythms and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) connectivity between thalamus and visual cortical networks as a function of brain amyloid burden, revealed by positron emission tomography and cognitive reserve, measured by educational attainment. The SMC participants were divided into 4 groups according to 2 factors: Education (Edu+ and Edu-) and Amyloid burden (Amy+ and Amy-). There was a statistical interaction (p < 0.05) between the two factors, and the subgroup analysis using estimated marginal means showed a positive association between the mentioned rs-fMRI connectivity and the posterior rsEEG alpha rhythms in the SMC participants with low brain amyloidosis and high CR (Amy-/Edu+). These results suggest that in SMC persons, early Alzheimer's disease amyloidosis may contrast the beneficial effects of cognitive reserve on neurophysiological oscillatory mechanisms at alpha frequencies and connectivity between the thalamus and visual cortical networks.


Alzheimer Disease , Amyloidosis , Cognitive Dysfunction , Humans , Aged , Alpha Rhythm , Alzheimer Disease/psychology , Electroencephalography/methods , Magnetic Resonance Imaging , Amyloid
2.
Neurobiol Aging ; 137: 78-93, 2024 May.
Article En | MEDLINE | ID: mdl-38452574

Oddball task-related EEG delta and theta responses are associated with frontal executive functions, which are significantly impaired in patients with dementia due to Parkinson's disease (PDD) and Lewy bodies (DLB). The present study investigated the oddball task-related EEG delta and theta responses in patients with PDD, DLB, and Alzheimer's disease dementia (ADD). During visual and auditory oddball paradigms, EEG activity was recorded in 20 ADD, 17 DLB, 20 PDD, and 20 healthy (HC) older adults. Event-related EEG power spectrum and phase-locking analysis were performed at the delta (1-4 Hz) and theta (4-7 Hz) frequency bands for target and nontarget stimuli. Compared to the HC persons, dementia groups showed lower frontal and central delta and theta power and phase-locking associated with task performance and neuropsychological test scores. Notably, this effect was more significant in the PDD and DLB than in the ADD. In conclusion, oddball task-related frontal and central EEG delta and theta responses may reflect frontal supramodal executive dysfunctions in PDD and DLB patients.


Alzheimer Disease , Lewy Body Disease , Parkinson Disease , Humans , Aged , Lewy Body Disease/psychology , Lewy Bodies , Electroencephalography
3.
Clin Neurophysiol ; 161: 159-172, 2024 May.
Article En | MEDLINE | ID: mdl-38492271

OBJECTIVES: Several persons experiencing post-covid-19 (post-COVID) with "brain fog" (e.g., fatigue, cognitive and psychiatric disorders, etc.) show abnormal resting-state electroencephalographic (rsEEG) rhythms reflecting a vigilance dysfunction. Here, we tested the hypothesis that in those post-COVID persons, abnormal rsEEG rhythms may occur even when cognitive and psychiatric disorders are absent. METHODS: The experiments were performed on post-COVID participants about one year after hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria included a "brain fog" claim, no pre-infection, and actual organic chronic disease. Matched controls (no COVID) were also enrolled. All participants underwent clinical/neuropsychological assessment (including fatigue assessment) and rsEEG recordings. The eLORETA freeware estimated regional rsEEG cortical sources at individual delta (<4 Hz), theta (4-7 Hz), and alpha (8-13 Hz) bands. Beta (14-30 Hz) and gamma (30-40 Hz) bands were pre-fixed. RESULTS: More than 90% of all post-COVID participants showed no cognitive or psychiatric disorders, and 75% showed ≥ 2 fatigue symptoms. The post-COVID group globally presented lower posterior rsEEG alpha source activities than the Control group. This effect was more significant in the long COVID-19 patients with ≥ 2 fatigue symptoms. CONCLUSIONS: In post-COVID patients with no chronic diseases and cognitive/psychiatric disorders, "brain fog" can be associated with abnormal posterior rsEEG alpha rhythms and subjective fatigue. SIGNIFICANCE: These abnormalities may be related to vigilance and allostatic dysfunctions.


COVID-19 , Electroencephalography , Humans , COVID-19/physiopathology , COVID-19/complications , Male , Female , Middle Aged , Electroencephalography/methods , Adult , Brain Waves/physiology , Fatigue/physiopathology , Fatigue/etiology , Aged , Rest/physiology , Brain/physiopathology , Post-Acute COVID-19 Syndrome
4.
Neurobiol Aging ; 137: 19-37, 2024 May.
Article En | MEDLINE | ID: mdl-38402780

Are posterior resting-state electroencephalographic (rsEEG) alpha rhythms sensitive to the Alzheimer's disease mild cognitive impairment (ADMCI) progression at a 6-month follow-up? Clinical, cerebrospinal, neuroimaging, and rsEEG datasets in 52 ADMCI and 60 Healthy old seniors (equivalent groups for demographic features) were available from an international archive (www.pdwaves.eu). The ADMCI patients were arbitrarily divided into two groups: REACTIVE and UNREACTIVE, based on the reduction (reactivity) in the posterior rsEEG alpha eLORETA source activities from the eyes-closed to eyes-open condition at ≥ -10% and -10%, respectively. 75% of the ADMCI patients were REACTIVE. Compared to the UNREACTIVE group, the REACTIVE group showed (1) less abnormal posterior rsEEG source activity during the eyes-closed condition and (2) a decrease in that activity at the 6-month follow-up. These effects could not be explained by neuroimaging and neuropsychological biomarkers of AD. Such a biomarker might reflect abnormalities in cortical arousal in quiet wakefulness to be used for clinical studies in ADMCI patients using 6-month follow-ups.


Alzheimer Disease , Cognitive Dysfunction , Humans , Alpha Rhythm , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Follow-Up Studies , Rest , Electroencephalography/methods , Cognitive Dysfunction/diagnosis , Biomarkers , Cerebral Cortex
5.
Lancet Neurol ; 23(3): 302-312, 2024 Mar.
Article En | MEDLINE | ID: mdl-38365381

The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.


Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , Europe , Biomarkers , Consensus , Societies, Scientific
6.
Neurobiol Aging ; 135: 1-14, 2024 Mar.
Article En | MEDLINE | ID: mdl-38142464

Here, we hypothesized that the reactivity of posterior resting-state electroencephalographic (rsEEG) alpha rhythms during the transition from eyes-closed to -open condition might be lower in patients with Parkinson's disease dementia (PDD) than in patients with Alzheimer's disease dementia (ADD). A Eurasian database provided clinical-demographic-rsEEG datasets in 73 PDD patients, 35 ADD patients, and 25 matched cognitively unimpaired (Healthy) persons. The eLORETA freeware was used to estimate cortical rsEEG sources. Results showed substantial (greater than -10%) reduction (reactivity) in the posterior alpha source activities from the eyes-closed to the eyes-open condition in 88% of the Healthy seniors, 57% of the ADD patients, and only 35% of the PDD patients. In these alpha-reactive participants, there was lower reactivity in the parietal alpha source activities in the PDD group than in the healthy control seniors and the ADD patients. These results suggest that PDD patients show poor reactivity of mechanisms desynchronizing posterior rsEEG alpha rhythms in response to visual inputs. That neurophysiological biomarker may provide an endpoint for (non) pharmacological interventions for improving vigilance regulation in those patients.


Alzheimer Disease , Dementia , Parkinson Disease , Humans , Alpha Rhythm/physiology , Parkinson Disease/complications , Dementia/etiology , Cerebral Cortex/physiology , Rest/physiology , Electroencephalography/methods
7.
Cogn Neurodyn ; 17(6): 1621-1635, 2023 Dec.
Article En | MEDLINE | ID: mdl-37974589

Objectives Working memory performances are based on brain functional connectivity, so that connectivity may be deranged in individuals with mild cognitive impairment (MCI) and patients with dementia due to Alzheimer's disease (ADD). Here we tested the hypothesis of abnormal functional connectivity as revealed by the imaginary part of coherency (ICoh) at electrode pairs from event-related electroencephalographic oscillations in ADD and MCI patients. Methods The study included 43 individuals with MCI, 43 with ADD, and 68 demographically matched healthy controls (HC). Delta, theta, alpha, beta, and gamma bands event-related ICoh was measured during an oddball paradigm. Inter-hemispheric, midline, and intra-hemispheric ICoh values were compared in ADD, MCI, and HC groups. Results The main results of the present study can be summarized as follows: (1) A significant increase of midline frontal and temporal theta coherence in the MCI group as compared to the HC group; (2) A significant decrease of theta, delta, and alpha intra-hemispheric coherence in the ADD group as compared to the HC and MCI groups; (3) A significant decrease of theta midline coherence in the ADD group as compared to the HC and MCI groups; (4) Normal inter-hemispheric coherence in the ADD and MCI groups. Conclusions Compared with the MCI and HC, the ADD group showed disrupted event-related intra-hemispheric and midline low-frequency band coherence as an estimate of brain functional dysconnectivity underlying disabilities in daily living. Brain functional connectivity during attention and short memory demands is relatively resilient in elderly subjects even with MCI (with preserved abilities in daily activities), and it shows reduced efficiency at multiple operating oscillatory frequencies only at an early stage of ADD. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09920-0.

8.
Clin Neurophysiol ; 156: 19-27, 2023 12.
Article En | MEDLINE | ID: mdl-37844524

OBJECTIVE: Parietal resting-state electroencephalographic (rsEEG) alpha (8-10 Hz) source connectivity is abnormal in HIV-positive persons. Here we tested whether this abnormality may be associated with subcortical white matter vascular lesions in the cerebral hemispheres. METHODS: Clinical, rsEEG, and magnetic resonance imaging (MRI) datasets in 38 HIV-positive persons and clinical and rsEEG datasets in 13 healthy controls were analyzed. Radiologists visually evaluated the subcortical white matter hyperintensities from T2-weighted FLAIR MRIs (i.e., Fazekas scale). In parallel, neurophysiologists estimated the eLORETA rsEEG source lagged linear connectivity from parietal cortical regions of interest. RESULTS: Compared to the HIV participants with no/negligible subcortical white matter hyperintensities, the HIV participants with mild/moderate subcortical white matter hyperintensities showed lower parietal interhemispheric rsEEG alpha lagged linear connectivity. This effect was also observed in HIV-positive persons with unimpaired cognition. This rsEEG marker allowed good discrimination (area under the receiver operating characteristic curve > 0.80) between the HIV-positive individuals with different amounts of subcortical white matter hyperintensities. CONCLUSIONS: The parietal rsEEG alpha source connectivity is associated with subcortical white matter vascular lesions in HIV-positive persons, even without neurocognitive disorders. SIGNIFICANCE: Those MRI-rsEEG markers may be used to screen HIV-positive persons at risk of neurocognitive disorders.


Alzheimer Disease , HIV Infections , White Matter , Humans , Cerebral Cortex/physiology , White Matter/diagnostic imaging , Alzheimer Disease/psychology , Electroencephalography/methods , Magnetic Resonance Imaging , HIV Infections/diagnostic imaging
9.
Cereb Cortex ; 33(20): 10514-10527, 2023 Oct 09.
Article En | MEDLINE | ID: mdl-37615301

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.

10.
Neurotherapeutics ; 20(4): 975-1000, 2023 07.
Article En | MEDLINE | ID: mdl-37436580

As of 2022, individuals age 65 and older represent approximately 10% of the global population [1], and older adults make up more than one third of anesthesia and surgical cases in developed countries [2, 3]. With approximately > 234 million major surgical procedures performed annually worldwide [4], this suggests that > 70 million surgeries are performed on older adults across the globe each year. The most common postoperative complications seen in these older surgical patients are perioperative neurocognitive disorders including postoperative delirium, which are associated with an increased risk for mortality [5], greater economic burden [6, 7], and greater risk for developing long-term cognitive decline [8] such as Alzheimer's disease and/or related dementias (ADRD). Thus, anesthesia, surgery, and postoperative hospitalization have been viewed as a biological "stress test" for the aging brain, in which postoperative delirium indicates a failed stress test and consequent risk for later cognitive decline (see Fig. 3). Further, it has been hypothesized that interventions that prevent postoperative delirium might reduce the risk of long-term cognitive decline. Recent advances suggest that rather than waiting for the development of postoperative delirium to indicate whether a patient "passed" or "failed" this stress test, the status of the brain can be monitored in real-time via electroencephalography (EEG) in the perioperative period. Beyond the traditional intraoperative use of EEG monitoring for anesthetic titration, perioperative EEG may be a viable tool for identifying waveforms indicative of reduced brain integrity and potential risk for postoperative delirium and long-term cognitive decline. In principle, research incorporating routine perioperative EEG monitoring may provide insight into neuronal patterns of dysfunction associated with risk of postoperative delirium, long-term cognitive decline, or even specific types of aging-related neurodegenerative disease pathology. This research would accelerate our understanding of which waveforms or neuronal patterns necessitate diagnostic workup and intervention in the perioperative period, which could potentially reduce postoperative delirium and/or dementia risk. Thus, here we present recommendations for the use of perioperative EEG as a "predictor" of delirium and perioperative cognitive decline in older surgical patients.


Emergence Delirium , Neurodegenerative Diseases , Humans , Aged , Emergence Delirium/epidemiology , Emergence Delirium/prevention & control , Brain/surgery , Aging , Electroencephalography , Intensive Care Units
11.
Neurobiol Aging ; 130: 70-79, 2023 Oct.
Article En | MEDLINE | ID: mdl-37473580

Here, we tested that standard eyes-closed resting-state electroencephalographic (rsEEG) rhythms may characterize patients with mild cognitive impairment due to chronic kidney disease at stages 3-4 (CKDMCI-3&4) in relation to CKDMCI patients under hemodialysis (CKDMCI-H) and mild cognitive impairment (MCI) patients with cerebrovascular disease (CVMCI). Clinical and rsEEG data in 22 CKDMCI-3&4, 15 CKDMCI-H, 18 CVMCI, and 30 matched healthy control (HC) participants were available in a national archive. Spectral rsEEG power density was calculated from delta to gamma frequency bands at scalp electrodes. Results showed that (1) all MCI groups over the HC group showed decreased occipital rsEEG alpha power density; (2) compared to the HC and CVMCI groups, the 2 CKDMCI groups had higher rsEEG delta-theta power density; and (3) the CKDMCI-3&4 group showed the lowest parietal rsEEG alpha power density. The present rsEEG measures may be useful to monitor the impact of circulating uremic toxins on brain regulation of cortical arousal for quiet vigilance in CKDMCI patients.


Alzheimer Disease , Cognitive Dysfunction , Renal Insufficiency, Chronic , Humans , Rest/physiology , Electroencephalography/methods , Cognitive Dysfunction/etiology , Brain , Alzheimer Disease/psychology , Cerebral Cortex/physiology
13.
Alzheimers Dement ; 19(7): 3186-3202, 2023 07.
Article En | MEDLINE | ID: mdl-37096339

INTRODUCTION: Operationalized research criteria for mild cognitive impairment with Lewy bodies (MCI-LB) were published in 2020. The aim of this systematic review and meta-analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI-LB set out in the criteria. METHODS: MEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI-LB. RESULTS: Fifty-seven articles were included. The meta-analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta-iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers. DISCUSSION: The available evidence largely supports the current diagnostic criteria for MCI-LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research. HIGHLIGHTS: A meta-analysis of the diagnostic features of MCI-LB was carried out. The four core clinical features were more common in MCI-LB than MCI-AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI-LB. More evidence is needed for the proposed biomarkers. FDG-PET and quantitative EEG show promise as diagnostic biomarkers in MCI-LB.


Alzheimer Disease , Cognitive Dysfunction , Lewy Body Disease , Humans , Alzheimer Disease/diagnosis , Lewy Bodies , Sensitivity and Specificity , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Biomarkers , Lewy Body Disease/diagnostic imaging
14.
Front Aging Neurosci ; 15: 780014, 2023.
Article En | MEDLINE | ID: mdl-36776437

Introduction: Graph theory models a network by its nodes (the fundamental unit by which graphs are formed) and connections. 'Degree' hubs reflect node centrality (the connection rate), while 'connector' hubs are those linked to several clusters of nodes (mainly long-range connections). Methods: Here, we compared hubs modeled from measures of interdependencies of between-electrode resting-state eyes-closed electroencephalography (rsEEG) rhythms in normal elderly (Nold) and Alzheimer's disease dementia (ADD) participants. At least 5 min of rsEEG was recorded and analyzed. As ADD is considered a 'network disease' and is typically associated with abnormal rsEEG delta (<4 Hz) and alpha rhythms (8-12 Hz) over associative posterior areas, we tested the hypothesis of abnormal posterior hubs from measures of interdependencies of rsEEG rhythms from delta to gamma bands (2-40 Hz) using eLORETA bivariate and multivariate-directional techniques in ADD participants versus Nold participants. Three different definitions of 'connector' hub were used. Results: Convergent results showed that in both the 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 participants than in Nold participants. Discussion: In conclusion, independent methodologies and hub definitions suggest that ADD patients may be characterized by low outward 'directionality' of partially preserved parietal 'degree' and 'connector' hubs derived from rsEEG alpha rhythms.

15.
Sensors (Basel) ; 23(4)2023 Feb 08.
Article En | MEDLINE | ID: mdl-36850494

Virtual reality has gained attention as an effective tool for cognitive, motor, and daily activity rehabilitation in patients with major neurocognitive disorder (M-NCD). The first objective of this study was to check for differences between M-NCD caused by degenerative and non-degenerative conditions (DC and NDC, respectively) in terms of relearning four functional living skills (FLSs), by means of a non-immersive virtual reality training (VRT). The second purpose was to verify whether spontaneous transfer from the virtual environment to the real environment occurred. Four FLS apps were developed in our institute (Information, Suitcase, Medicine, and Supermarket). A nonrandomized interventional study was carried out, comparing experimental and control groups (EG and CG, respectively). The study included three phases: in vivo test at T1; VRT at T2 only for EG; in vivo test at T3. During the in vivo test, the four FLSs were assessed in their natural environments. Both EG-DC and EG-NDC significantly improved in all of the VRT variable scores (the EG-NDC group seemed to show better outcomes than the EG-DC group). Moderate-to-high satisfaction with the VRT was reported. EG-DC and EG-NDC also enhanced their performances in the in vivo test. No statistically significant differences between them were found. CG-DC and CG-NDC improved only in the execution time of Information in the in vivo test. These findings confirm the ecological validity of VRT for FLSs.


Dementia , Virtual Reality , Humans , Patients , Activities of Daily Living , Biological Assay
16.
Psychophysiology ; 60(6): e14281, 2023 06.
Article En | MEDLINE | ID: mdl-36852668

Mirror visual feedback (MVF) technique consists in placing a mirror in a person's body midline to induce the illusion of bilateral synchronous movements of the limbs during actual unilateral movements. A recent electroencephalographical (EEG) study demonstrated that MVF-induced illusion was related to the event-related desynchronization (ERD) of alpha (8-12 Hz) rhythms (cortical activation) at the central and parietal scalp electrodes ipsilateral to the unilateral right finger movements. In the present study, we re-analyzed those data to localize the cortical sources of alpha ERD during the anticipation and experience of the MVF-induced illusion of index finger movements. To this aim, the exact Low-Resolution Brain Electromagnetic Tomography freeware was used for the estimation of the cortical sources of the alpha ERD. Results showed that as compared to the condition without MVF, the MVF condition was characterized by greater (p < .01, uncorrected) alpha ERD sources in right frontopolar areas during the anticipation of the MVF-induced illusion of left movements. The MVF condition was also characterized by greater (p < .05, corrected) alpha ERD sources in right premotor, primary somatomotor, and posterior inferior parietal areas during both the anticipation and experience of that MVF-induced illusion. These findings suggest that the MVF-induced illusory experience of left finger movements may be due to dynamic changes in alpha ERD in associative, premotor, somatomotor, and visuomotor frontal-parietal areas located in the hemisphere contralateral to the mirrored motor acts.


Alpha Rhythm , Illusions , Humans , Feedback, Sensory/physiology , Electroencephalography , Movement/physiology
17.
Alzheimers Dement ; 19(5): 2182-2196, 2023 05.
Article En | MEDLINE | ID: mdl-36642985

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.


Alzheimer Disease , Humans , Alzheimer Disease/pathology , Brain/pathology , Biomarkers , Disease Progression
18.
Ageing Res Rev ; 84: 101819, 2023 02.
Article En | MEDLINE | ID: mdl-36526257

Acetylcholinesterase inhibitors (ChEI) are the global standard of care for the symptomatic treatment of Alzheimer's disease (AD) and show significant positive effects in neurodegenerative diseases with cognitive and behavioral symptoms. Although experimental and large-scale clinical evidence indicates the potential long-term efficacy of ChEI, primary outcomes are generally heterogeneous across outpatient clinics and regional healthcare systems. Sub-optimal dosing or slow tapering, heterogeneous guidelines about the timing for therapy initiation (prodromal versus dementia stages), healthcare providers' ambivalence to treatment, lack of disease awareness, delayed medical consultation, prescription of ChEI in non-AD cognitive disorders, contribute to the negative outcomes. We present an evidence-based overview of determinants, spanning genetic, molecular, and large-scale networks, involved in the response to ChEI in patients with AD and other neurodegenerative diseases. A comprehensive understanding of cerebral and retinal cholinergic system dysfunctions along with ChEI response predictors in AD is crucial since disease-modifying therapies will frequently be prescribed in combination with ChEI. Therapeutic algorithms tailored to genetic, biological, clinical (endo)phenotypes, and disease stages will help leverage inter-drug synergy and attain optimal combined response outcomes, in line with the precision medicine model.


Alzheimer Disease , Neurodegenerative Diseases , Humans , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/diagnosis , Acetylcholinesterase/therapeutic use , Neurodegenerative Diseases/drug therapy , Precision Medicine
19.
Clin EEG Neurosci ; 54(1): 21-35, 2023 Jan.
Article En | MEDLINE | ID: mdl-36413420

Abnormalities in cortical sources of resting-state eyes closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10-20 montage) with 19 scalp electrodes characterized Alzheimer's disease (AD) from preclinical to dementia stages. An intriguing rsEEG application is the monitoring and evaluation of AD progression in large populations with few electrodes in low-cost devices. Here we evaluated whether the above-mentioned abnormalities can be observed from fewer scalp electrodes in patients with mild cognitive impairment due to AD (ADMCI). Clinical and rsEEG data acquired in hospital settings (10-20 montage) from 75 ADMCI participants and 70 age-, education-, and sex-matched normal elderly controls (Nold) were available in an Italian-Turkish archive (PDWAVES Consortium; www.pdwaves.eu). Standard spectral fast fourier transform (FFT) analysis of rsEEG data for individual delta, theta, and alpha frequency bands was computed from 6 monopolar scalp electrodes to derive bipolar C3-P3, C4-P4, P3-O1, and P4-O2 markers. The ADMCI group showed increased delta and decreased alpha power density at the C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels compared to the Nold group. 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. Standard rsEEG power density computed from six posterior bipolar channels characterized ADMCI status. These results may pave the way toward diffuse clinical applications in health monitoring of dementia using low-cost EEG systems with a strict number of electrodes in lower- and middle-income countries.


Alzheimer Disease , Cognitive Dysfunction , Humans , Aged , Electroencephalography/methods , Rest , Cerebral Cortex , Cognitive Dysfunction/diagnosis
...