Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% ...to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies in vivo, using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α‐synuclein (α‐SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α‐SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α‐SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.
Making an accurate diagnosis of dementia in Parkinson’s disease (PD-D) patients is a challenge that neurologists will have to face in the coming years. In 2007, a Task force of the Movement Disorders ...Society proposed operational diagnostic criteria for the diagnosis of PD-D, consisting of step I and step II. We assessed the validity of step I with reference to the diagnosis made after a formal neuropsychological evaluation and by applying the current gold standard for the diagnosis of PD-D (DSM IV). Step I had a sensitivity of 78% and a specificity of 95.5%. Step I displayed a positive predictive value of 70%, a negative predictive value of 97%, and an accuracy of 93.4%. The clinimetric properties observed in our setting suggest that step I may be considered as a good screening tool (negative predictive value of 97%); however, using step I alone to make a diagnosis of PD-D may lead to an overestimation of dementia in PD, particularly in patients with considerable dysexecutive deficits (positive predictive value of 70%). In conclusion, formal neuropsychology and longitudinal follow-up are still required for the diagnosis and categorization of dementia in PD.
Abstract The aim of this retrospective exploratory study was that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with dementia due to ...Alzheimer’s disease (ADD), Parkinson’s disease (PDD), and Lewy body (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were available in an international archive. Demography, education, and Mini Mental State Evaluation score were not different between the patient groups. Individual alpha frequency peak (IAF) determined the delta, theta, alpha1, alpha2, and alpha3 frequency bands. Fixed beta1, beta2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic curves. Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD. These groups also showed higher occipital delta source activities, but this effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior delta and alpha sources allowed good classification accuracy (approximately 0.85-0.90) between the Nold subjects and patients, and between ADD and PDD patients. In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. Future prospective cross-validation studies should test these rsEEG markers for clinical applications and drug discovery.
Previous evidence showed abnormal posterior sources of resting-state delta (<4 Hz) and alpha (8–12 Hz) rhythms in patients with Alzheimer's disease with dementia (ADD), Parkinson's disease with ...dementia (PDD), and Lewy body dementia (DLB), as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis of additional abnormalities in functional cortical connectivity computed in those sources, in ADD, considered as a “disconnection cortical syndrome”, in comparison with PDD and DLB. Resting-state eyes-closed electroencephalographic (rsEEG) rhythms had been collected in 42 ADD, 42 PDD, 34 DLB, and 40 normal healthy older (Nold) participants. Exact low-resolution brain electromagnetic tomography (eLORETA) freeware estimated the functional lagged linear connectivity (LLC) from rsEEG cortical sources in delta, theta, alpha, beta, and gamma bands. The area under receiver operating characteristic (AUROC) curve indexed the classification accuracy between Nold and diseased individuals (only values >0.7 were considered). Interhemispheric and intrahemispheric LLCs in widespread delta sources were abnormally higher in the ADD group and, unexpectedly, normal in DLB and PDD groups. Intrahemispheric LLC was reduced in widespread alpha sources dramatically in ADD, markedly in DLB, and moderately in PDD group. Furthermore, the interhemispheric LLC in widespread alpha sources showed lower values in ADD and DLB than PDD groups. At the individual level, AUROC curves of LLC in alpha sources exhibited better classification accuracies for the discrimination of ADD versus Nold individuals (0.84) than for DLB versus Nold participants (0.78) and PDD versus Nold participants (0.75). Functional cortical connectivity markers in delta and alpha sources suggest a more compromised neurophysiological reserve in ADD than DLB, at both group and individual levels.
Previous evidence has shown different resting-state eyes-closed electroencephalographic delta (<4 Hz) and alpha (8–10.5 Hz) source connectivity in subjects with dementia due to Alzheimer's (ADD) and ...Lewy body (DLB) diseases. The present study tested if the same differences may be observed in the prodromal stages of mild cognitive impairment (MCI). Here, clinical and resting-state eyes-closed electroencephalographic data in age-, gender-, and education-matched 30 ADMCI, 23 DLBMCI, and 30 healthy elderly (Nold) subjects were available in our international archive. Mini-Mental State Evaluation (MMSE) score was matched in the ADMCI and DLBMCI groups. The eLORETA freeware estimated delta and alpha source connectivity by the tool called lagged linear connectivity (LLC). Area under receiver operating characteristic curve (AUROCC) indexed the classification accuracy among individuals. Results showed that widespread interhemispheric and intrahemispheric LLC solutions in alpha sources were abnormally lower in both MCI groups compared with the Nold group, but with no differences were found between the 2 MCI groups. AUROCCs of LLC solutions in alpha sources exhibited significant accuracies (0.72–0.75) in the discrimination of Nold versus ADMCI-DLBMCI individuals, but not between the 2 MCI groups. These findings disclose similar abnormalities in ADMCI and DLBMCI patients as revealed by alpha source connectivity. It can be speculated that source connectivity mostly reflects common cholinergic impairment in prodromal state of both AD and DLB, before a substantial dopaminergic derangement in the dementia stage of DLB.
•We evaluated the abnormalities in functional cortical connectivity computed in rsEEG sources in subjects with Mild Cognitive Impairment due to Alzheimer’s and Lewy Body disease.•At the group level, EEG markers of functional cortical connectivity were abnormally lower in in Alzheimer’s Disease (ADD) and Lewy Body Disease (DLB) patients compared to healthy elderly subjects (Nold).•At the group level, EEG markers of functional cortical connectivity were similar between in ADD and DLB patients compared to Nold subjects.•At the individual level, EEG marker of functional cortical connectivity exhibited better classification accuracies for the discrimination of ADD versus Nold, and DLB versus Nold, but not between ADD and DLB.
The present study tested the hypothesis that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms reveal different abnormalities in cortical neural synchronization in ...groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and dementia with Lewy bodies (DLBMCI) as compared to cognitively normal elderly (Nold) subjects. Clinical and rsEEG data in 30 ADMCI, 23 DLBMCI, and 30 Nold subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) score was matched between the ADMCI and DLBMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROCC) classified these sources across individuals. Compared to Nold, IAF showed marked slowing in DLBMCI and moderate in ADMCI. Furthermore, the posterior alpha 2 and alpha 3 source activities were more abnormal in the ADMCI than the DLBMCI group, while widespread delta source activities were more abnormal in the DLBMCI than the ADMCI group. The posterior delta and alpha sources correlated with the MMSE score and correctly classified the Nold and MCI individuals (area under the ROCC >0.85). In conclusion, the ADMCI and DLBMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test the clinical validity of these rsEEG markers.
The aim of this retrospective and exploratory study was that the cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might reveal different abnormalities in cortical ...neural synchronization in groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and Parkinson's disease (PDMCI) as compared to healthy subjects. Clinical and rsEEG data of 75 ADMCI, 75 PDMCI, and 75 cognitively normal elderly (Nold) subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) was matched between the ADMCI and PDMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROC) classified these sources across individuals. Results showed that compared to the Nold group, the posterior alpha2 and alpha3 source activities were more abnormal in the ADMCI than the PDMCI group, while the parietal delta source activities were more abnormal in the PDMCI than the ADMCI group. The parietal delta and alpha sources correlated with MMSE score and correctly classified the Nold and diseased individuals (area under the ROC = 0.77-0.79). In conclusion, the PDMCI and ADMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test these rsEEG markers for clinical applications and drug discovery.
We hypothesized that dopamine neuromodulation might affect cortical excitability in Parkinson's disease (PD) patients set in quiet wakefulness, as revealed by resting state eyes-closed ...electroencephalographic (rsEEG) rhythms at alpha frequencies (8–12 Hz). Clinical and rsEEG rhythms in PD with dementia (N = 35), PD with mild cognitive impairment (N = 50), PD with normal cognition (N = 35), and normal (N = 50) older adults were available from an international archive. Cortical rsEEG sources were estimated by exact low-resolution brain electromagnetic tomography. Compared with the normal older group, the PD groups showed reduced occipital alpha sources and increased widespread delta (<4 Hz) sources. Widespread frontal and temporal alpha sources exhibited an increase in PD with dementia compared with PD with mild cognitive impairment and PD with normal cognition groups, as function of dopamine depletion severity, typically greater in the former than the latter groups. A daily dose of levodopa induced a widespread reduction in cortical delta and alpha sources in a subgroup of 13 PD patients under standard chronic dopaminergic regimen. In PD patients in quiet wakefulness, alpha cortical source activations may reflect an excitatory effect of dopamine neuromodulation.
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