Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis.

Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.

Cognitive, psychological, and physiological effects of a web-based mindfulness intervention in older adults during the COVID-19 pandemic: an open study.

BACKGROUND: The development of effective strategies to maintain good mental health of older adults is a public health priority. Mindfulness-based interventions have the potential to improve psychological well-being and cognitive functions of older adults, but little is known about the effect of such interventions when delivered through internet. During the COVID-19 pandemic we evaluated short- and long-term cognitive, psychological, and physiological effects of a mindfulness-based intervention (MBI) delivered via web-based videoconference in healthy older adults. METHODS: Fifty older adults participated in an 8-week MBI, which comprised structured 2-h weekly group sessions. A comprehensive evaluation encompassing cognitive (verbal memory, attention and processing speed, executive functions) and psychological assessments (depression and anxiety symptoms, mindfulness, worries, emotion regulation strategies, well-being, interoceptive awareness and sleep) was conducted. Additionally, electroencephalography (EEG) data were recorded before and after the MBI and at the 6-month follow-up (T6). Data were analyzed using an intention-to-treat approach, using linear mixed models adjusted for age. The effect size for time was computed as omega squared. RESULTS: We observed significant improvements from pre-MBI to post-MBI and at the T6 across several measures. These improvements were notable in the areas of verbal memory (California Verbal Learning Test, p ≤ .007), attention and executive functions (Trail Making Test A and BA, p < .050), interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness, p = .0002 for self-regulation and p < .05 for noticing, body listening, and trusting dimensions), and rumination (Heidelberg Form for Emotion Regulation Strategies, p = .018). These changes were associated with low to medium effect size. Moreover, we observed significant changes in EEG patterns, with a decrease in alpha1 (p = .004) and an increase in alpha2 (p < .0001) from pre-MBI to T6. Notably, improvements in TMTBA and rumination were correlated with the decrease in alpha1 (p < .050), while improvements in TMTA were linked to the increase in alpha2 (p = .025). CONCLUSIONS: The results of our study show that a web-based MBI in older adults leads to improvements in cognitive and psychological measures, with associated modulations in specific brain rhythms. While these findings are promising, further controlled studies are required to validate these preliminary results. TRIAL REGISTRATION: The trial has been registered with the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT05941143 on July 12, 2023.

Measures of resting state EEG rhythms for clinical trials in Alzheimer's disease: Recommendations of an expert panel.

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes.

The role of dyadic cognitive report and subjective cognitive decline in early ADRD clinical research and trials: Current knowledge, gaps, and recommendations.

Efficient identification of cognitive decline and Alzheimer's disease (AD) risk in early stages of the AD disease continuum is a critical unmet need. Subjective cognitive decline is increasingly recognized as an early symptomatic stage of AD. Dyadic cognitive report, including subjective cognitive complaints (SCC) from a participant and an informant/study partner who knows the participant well, represents an accurate, reliable, and efficient source of data for assessing risk. However, the separate and combined contributions of self- and study partner report, and the dynamic relationship between the two, remains unclear. The Subjective Cognitive Decline Professional Interest Area within the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment convened a working group focused on dyadic patterns of subjective report. Group members identified aspects of dyadic-report information important to the AD research field, gaps in knowledge, and recommendations. By reviewing existing data on this topic, we found evidence that dyadic measures are associated with objective measures of cognition and provide unique information in preclinical and prodromal AD about disease stage and progression and AD biomarker status. External factors including dyad (participant-study partner pair) relationship and sociocultural factors contribute to these associations. We recommend greater dyad report use in research settings to identify AD risk. Priority areas for future research include (1) elucidation of the contributions of demographic and sociocultural factors, dyad type, and dyad relationship to dyad report; (2) exploration of agreement and discordance between self- and study partner report across the AD syndromic and disease continuum; (3) identification of domains (e.g., memory, executive function, neuropsychiatric) that predict AD risk outcomes and differentiate cognitive impairment due to AD from other impairment; (4) development of best practices for study partner engagement; (5) exploration of study partner report as AD clinical trial endpoints; (6) continued development, validation, and optimization, of study partner report instruments tailored to the goals of the research and population.

What electrophysiology tells us about Alzheimer's disease: a window into the synchronization and connectivity of brain neurons.

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer's disease (AD), despite a surge in recent validated evidence. This position paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity, reflecting thalamocortical and corticocortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies.

Increasing hippocampal atrophy and cerebrovascular damage is differently associated with functional cortical coupling in MCI patients.

The aim of this study was to assess the changes of intrahemispheric and interhemispheric linear spectral electroencephalography (EEG) coherence associated with increasing hippocampal atrophy (HA) and white matter hyperintensities (WMHs) in patients with mild cognitive impairment (MCI). Eighty-five MCI patients underwent clinical and neuropsychologic assessment, EEG recordings, and magnetic resonance imaging. Intrahemispheric (fronto-temporal, temporo-parietal, and fronto-parietal) and interhemispheric (frontal, temporal, and parietal) linear EEG coherence was computed. MCI patients were categorized into classes of increasing HA and WMHs on the basis of tertile distribution of volume loss (high, mid, and low). Neuropsychologic tests were also gathered and compared in MCI subgroups. As expected, MCI patients with high WMHs had poorer performance on visuospatial and cognitive flexibility, whereas those with high HA failed on memory tests. Significant differences of EEG functional coupling were present in the fronto-temporal network in patients with high WMHs and high HA, but without a different pattern. In high WMHs the EEG coherence in low frequencies was increased (with the exception of alpha1 band), whereas coherence in the fast frequencies was decreased proportional to increasing damage. In high HA a change of coherence was present in the delta and alpha2 frequency bands that was not proportional to HA, fast frequencies being unaffected. Our results show a lateralization (right hemisphere for cerebrovascular disease and left hemisphere for hippocampal atrophy) of the pathologic modifications of functional coupling.

Available and future treatments for atypical parkinsonism. A systematic review.

AIMS: Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy (MSA), Parkinson's disease with dementia (PDD), and Lewy body dementia with (LBD), remains exceedingly low. The present work overviews the most influential research literature collected on MEDLINE, ISI Web of Science, Cochrane Library, and Scopus for available treatment in atypical parkinsonisms without time restriction. DISCUSSION: Transdermal rotigotine, autologous mesenchymal stem cells, tideglusib, and coenzyme Q10 along with donepezil, rivastigmine, memantine, and the deep brain stimulation have shown some benefits in alleviating symptoms in APS. Moreover, many new clinical trials are ongoing testing microtubule stabilizer, antitau monoclonal antibody, tau acetylation inhibition, cell replacement, selective serotonin reuptake inhibitor, active immunization, inhibition of toxic α-synuclein oligomers formation, and inhibition of microglia. CONCLUSION: A detailed knowledge of the pathological mechanism underlying the disorders is needed, and disease-modifying therapies are required to offer better therapeutic options to physician and caregivers of APS patients.

Cerebrovascular disease and hippocampal atrophy are differently linked to functional coupling of brain areas: an EEG coherence study in MCI subjects.

The working hypothesis of paper is that the functional coupling of brain areas is combined with different neuroradiological substrates and has different clinical manifestations. 31 normal old subjects and 85 subjects with mild cognitive impairment (MCI) underwent EEG recordings and magnetic resonance imaging (MRI). Intrahemispheric and interhemispheric linear EEG coherences were computed. At first, all normal old and MCI subjects were compared. Subsequently, three subgroups of MCI were obtained based on neuroradiological substrate (subcortical cerebrovascular damage, MCI-CVD; cholinergic pathways vascular damage MCI-CHOL; and hippocampal atrophy, MCI-HIPP) and compared with a normal old sample matched for age, education and Mini-Mental State Examination score. The group of MCI subjects compared to normal old subjects shows: 1) decrease of intrahemispheric coherence in fronto-parietal regions (both right and left hemisphere); 2) increase of interhemispheric coherence on frontal regions in delta frequency; and 3) increase of interhemispheric coherence on temporal regions (from delta to alpha3 frequency bands). In the MCI subgroups, hippocampal atrophy is linked to an increase of interhemispheric coherence seen on frontal and temporal regions whereas subcortical CVD is linked to the largest decrease of coherence in fronto-parietal regions. MCI-CVD patients performed worst on Trail Making Test battery whereas MCI-HIPP patients were impaired on Rey word list delayed recall and Rey figure recall.

Brain vascular damage of cholinergic pathways and EEG markers in mild cognitive impairment.

We evaluated changes of brain rhythmicity correlating with the cerebrovascular damage of long-range (capsular tract) and short-range (medial and perisylvian tracts) cholinergic pathways in subjects with mild cognitive impairment (MCI). Ninety-four MCI subjects underwent electroencephalographic (EEG) recordings and magnetic resonance imaging (MRI). The EEG relative power spectrum was computed in delta, theta, alpha1, alpha2, alpha3, beta1, beta2, gamma frequency bands. White matter hyperintensities along each cholinergic tract was segmented on MRI. Three MCI subgroups were identified based on increasing damage. A significant increase of delta and theta power band was found in patients with the highest total cholinergic burden as well as in patients with highest capsular pathway damage; total load of cholinergic damage was also associated with decreased gamma power band. Alpha frequency was differentially affected: decrease of alpha3 power band was associated with the greatest damage of the capsular pathway whereas increase of alpha3 power band was associated with the greatest damage of the perisylvian pathway. Multiple regression linear analysis showed independent association of cholinergic damage with delta, theta and gamma frequency, not with alpha frequency. In conclusion, the damage of long-range and short range cholinergic tracts has possible different implications for cognitive functions in MCI subjects.

Cerebral PET glucose hypometabolism in subjects with mild cognitive impairment and higher EEG high-alpha/low-alpha frequency power ratio.

In Alzheimer's disease (AD) research, both 2-deoxy-2-(18F)fluoro-D-glucose (FDG) positron emission tomography (PET) and electroencephalography (EEG) are reliable investigational modalities. The aim of this study was to investigate the associations between EEG High-alpha/Low-alpha (H-alpha/L-alpha) power ratio and cortical glucose metabolism. A total of 23 subjects with mild cognitive impairment (MCI) underwent FDG-PET and EEG examinations. H-alpha/L-alpha power ratio was computed for each subject and 2 groups were obtained based on the increase of the power ratio. The subjects with higher H-alpha/L-alpha power ratio showed a decrease in glucose metabolism in the hub brain areas previously identified as typically affected by AD pathology. In subjects with higher H-alpha/L-alpha ratio and lower metabolism, a "double alpha peak" was identified in the EEG spectrum and a U-shaped correlation between glucose metabolism and increase of H-alpha/L-alpha power ratio has been found. Moreover, in this group, a conversion rate of 62.5% at 24 months was detected, significantly different from the chance percentage expected. The neurophysiological meaning of the interplay between alpha oscillations and glucose metabolism and the possible interest of the H-alpha/L-alpha power ratio as a clinical biomarker in AD have been discussed.

Electroencephalography-driven approach to prodromal Alzheimer's disease diagnosis: from biomarker integration to network-level comprehension.

Decay of the temporoparietal cortex is associated with prodromal Alzheimer's disease (AD). Additionally, shrinkage of the temporoparietal cerebral area has been connected with an increase in α3/α2 electroencephalogram (EEG) power ratio in prodromal AD. Furthermore, a lower regional blood perfusion has been exhibited in patients with a higher α3/α2 proportion when contrasted with low α3/α2 proportion. Furthermore, a lower regional blood perfusion and reduced hippocampal volume has been exhibited in patients with higher α3/α2 when contrasted with lower α3/α2 EEG power ratio. Neuropsychological evaluation, EEG recording, and magnetic resonance imaging were conducted in 74 patients with mild cognitive impairment (MCI). Estimation of cortical thickness and α3/α2 frequency power ratio was conducted for each patient. A subgroup of 27 patients also underwent single-photon emission computed tomography evaluation. In view of α3/α2 power ratio, the patients were divided into three groups. The connections among cortical decay, cerebral perfusion, and memory loss were evaluated by Pearson's r coefficient. Results demonstrated that higher α3/α2 frequency power ratio group was identified with brain shrinkage and cutdown perfusion inside the temporoparietal projections. In addition, decay and cutdown perfusion rate were connected with memory shortfalls in patients with MCI. MCI subgroup with higher α3/α2 EEG power ratio are at a greater risk to develop AD dementia.

Alpha rhythms in mild dements during visual delayed choice reaction time tasks: a MEG study.

Can simple delayed response tasks affect latency and amplitude of magnetoencephalographic midline alpha rhythms (6-12 Hz) in early dementia? We recruited 15 mild Alzheimer's disease (AD) and 10 vascular dementia (VaD) patients (paired mini mental state exam of 17-24). The control groups comprised 18 young and 22 elderly normal subjects. In the first task, a simple "cue" stimulus (one bit) was memorized along a brief delay period (3.5-5.5s) up to a "go" stimulus triggering (right or left) button press. In the second task, the "cue" stimulus remained available along the delay period. Event-related reduction in power of the alpha rhythms indexed the cortical activation (event-related desynchronization, ERD) for the trials associated with correct behavioral responses. Behavioral performances to both tasks were lower in the AD and VaD patients than in the normal subjects. In particular, just four AD and five VaD patients executed a sufficient amount of correct responses for the alpha ERD analysis, so they were included in a unique group. In both tasks, the alpha ERD peak was later in latency in the demented and normal elderly subjects than in the normal young subjects. Furthermore, the alpha ERD peak was stronger in amplitude in the demented patients than in the normal subjects. These results suggest that simple delayed response tasks during physiological recordings are quite difficult for patients even at an early dementia stage. Such difficulty may induce the abnormal amount of the related cortical activation in dementia as revealed by the alpha ERD.

Association of EEG, MRI, and regional blood flow biomarkers is predictive of prodromal Alzheimer's disease.

BACKGROUND: Thinning in the temporoparietal cortex, hippocampal atrophy, and a lower regional blood perfusion is connected with prodromal stage of Alzheimer's disease (AD). Of note, an increase of electroencephalography (EEG) upper/low alpha frequency power ratio has also been associated with these major landmarks of prodromal AD. METHODS: Clinical and neuropsychological assessment, EEG recording, and high-resolution three-dimensional magnetic resonance imaging were done in 74 grown up subjects with mild cognitive impairment. This information was gathered and has been assessed 3 years postliminary. EEG recording and perfusion single-photon emission computed tomography assessment was done in 27 subjects. Alpha3/alpha2 frequency power ratio, including cortical thickness, was figured for every subject. Contrasts in cortical thickness among the groups were assessed. Pearson's r relationship coefficient was utilized to evaluate the quality of the relationship between cortical thinning, brain perfusion, and EEG markers. RESULTS: The higher alpha3/alpha2 frequency power ratio group corresponded with more prominent cortical decay and a lower perfusional rate in the temporoparietal cortex. In a subsequent meetup after 3 years, these patients had AD. CONCLUSION: High EEG upper/low alpha power ratio was connected with cortical diminishing and lower perfusion in the temporoparietal brain area. The increase in EEG upper/low alpha frequency power ratio could be helpful in recognizing people in danger of conversion to AD dementia and this may be quality information in connection with clinical assessment.

Understanding early dementia: EEG, MRI, SPECT and memory evaluation.

BACKGROUND: An increase in the EEG upper/low α power ratio has been associated with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and to the atrophy of temporoparietal brain areas. Subjects with a higher α3/α2 frequency power ratio showed lower brain perfusion than in the low α3/α2 group. The two groups show significantly different hippocampal volumes and correlation with θ frequency activity. METHODS: Seventy-four adult subjects with MCI underwent clinical and neuropsychological evaluation, electroencephalogram (EEG) recording, and high resolution 3D magnetic resonance imaging (MRI). Twenty-seven of them underwent EEG recording and perfusion single-photon emission computed tomography (SPECT) evaluation. The α3/α2 power ratio and cortical thickness were computed for each subject. The difference in cortical thickness between the groups was estimated. RESULTS: In the higher upper/low α group, memory impairment was more pronounced in both the MRI group and the SPECT MCI groups. An increase in the production of θ oscillations was associated with greater interhemisperic coupling between temporal areas. It also correlated with greater cortical atrophy and lower perfusional rate in the temporoparietal cortex. CONCLUSION: High EEG upper/low α power ratio was associated with cortical thinning and lower perfusion in temporoparietal areas. Moreover, both atrophy and lower perfusion rate significantly correlated with memory impairment in MCI subjects. Therefore, the increase in the EEG upper/low α frequency power ratio could be useful in identifying individuals at risk for progression to AD dementia in a clinical context.

Mild Cognitive Impairment: Structural, Metabolical, and Neurophysiological Evidence of a Novel EEG Biomarker.

BACKGROUND: Recent studies demonstrate that the alpha3/alpha2 power ratio correlates with cortical atrophy, regional hypoperfusion, and memory impairment in subjects with mild cognitive impairment (MCI). METHODS: Evidences were reviewed in subjects with MCI, who underwent EEG recording, magnetic resonance imaging (MRI) scans, and memory evaluation. Alpha3/alpha2 power ratio (alpha2 8.9-10.9 Hz range; alpha3 10.9-12.9 Hz range), cortical thickness, linear EEG coherence, and memory impairment have been evaluated in a large group of 74 patients. A subset of 27 subjects within the same group also underwent single photon emission computed tomography (SPECT) evaluation. RESULTS: In MCI subjects with higher EEG upper/low alpha power ratio, a greater temporo-parietal and hippocampal atrophy was found as well as a decrease in regional blood perfusion and memory impairment. In this group, an increase of theta oscillations is associated with a greater interhemispheric coupling between temporal areas. CONCLUSION: The increase of alpha3/alpha2 power ratio is a promising novel biomarker in identifying MCI subjects at risk for Alzheimer's disease.

Electroencephalography reveals lower regional blood perfusion and atrophy of the temporoparietal network associated with memory deficits and hippocampal volume reduction in mild cognitive impairment due to Alzheimer's disease.

BACKGROUND: An increased electroencephalographic (EEG) upper/lower alpha power ratio has been associated with less regional blood perfusion, atrophy of the temporoparietal region of the brain, and reduction of hippocampal volume in subjects affected by mild cognitive impairment due to Alzheimer's disease as compared with subjects who do not develop the disease. Moreover, EEG theta frequency activity is quite different in these groups. This study investigated the correlation between biomarkers and memory performance. METHODS: EEG α3/α2 power ratio and cortical thickness were computed in 74 adult subjects with prodromal Alzheimer's disease. Twenty of these subjects also underwent assessment of blood perfusion by single-photon emission computed tomography (SPECT). Pearson's r was used to assess the correlation between cortical thinning, brain perfusion, and memory impairment. RESULTS: In the higher α3/α2 frequency power ratio group, greater cortical atrophy and lower regional perfusion in the temporoparietal cortex was correlated with an increase in EEG theta frequency. Memory impairment was more pronounced in the magnetic resonance imaging group and SPECT groups. CONCLUSION: A high EEG upper/low alpha power ratio was associated with cortical thinning and less perfusion in the temporoparietal area. Moreover, atrophy and less regional perfusion were significantly correlated with memory impairment in subjects with prodromal Alzheimer's disease. The EEG upper/lower alpha frequency power ratio could be useful for identifying individuals at risk for progression to Alzheimer's dementia and may be of value in the clinical context.

Human cortical responses during one-bit short-term memory. A high-resolution EEG study on delayed choice reaction time tasks.

OBJECTIVE: We investigated whether a very simple short-term memory (STM) demand induces a visible change of EEG rhythms over the two hemispheres. METHODS: High-resolution EEG was obtained in young adults during two delayed choice reaction time tasks. In the STM condition, a simple cue stimulus (one bit) was memorized along a brief delay period (3.5-5.5 s). The task was visuo-spatial in nature. RESULTS: In the control (NSTM) condition, the cue stimulus remained available along the delay period. Compared to the control condition, the theta power (4-6 Hz) decreased in left frontal and bilateral parietal areas (delay period). Furthermore, low alpha power (6-8 Hz) decreased in bilateral frontal and left parietal areas, while high alpha power (10-12 Hz) decreased in the left fronto-parietal areas. CONCLUSIONS: The decrease of the alpha power is as an expression of the efficient information transfer within thalamo-cortical pathways. The significance of the study stands in the fact that even a very simple STM task (only one bit to be memorized) revealed changes in fronto-parietal theta and alpha rhythms.

Rotigotine is safe and efficacious in Atypical Parkinsonism Syndromes induced by both α-synucleinopathy and tauopathy.

Transdermal rotigotine (RTG) is a non-ergot dopamine agonist (D3>D2>D1), and is indicated for use in early and advanced Parkinson's disease (PD). RTG patch has many potential advantages due to the immediacy of onset of the therapeutic effect. Of note, intestinal absorption is not necessary and drug delivery is constant, thereby avoiding drug peaks and helping patient compliance. In turn, transdermal RTG seems a suitable candidate in the treatment of atypical Parkinsonian disorders (APS). Fifty-one subjects with a diagnosis of APS were treated with transdermal RTG. The diagnoses were: Parkinson's disease with dementia, multiple system atrophy Parkinsonian type, multiple system atrophy cerebellar type, progressive supranuclear palsy, corticobasal degeneration, Lewy body dementia, and frontotemporal dementia with Parkinsonism. Patients were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS; part III), Neuropsychiatric Inventory (NPI), and mini-mental state examination (MMSE) and all adverse events (AEs) were recorded. Patients treated with RTG showed an overall decrease of UPDRS III scores without increasing behavioral disturbances. Main AEs were hypotension, nausea, vomiting, drowsiness, tachycardia, and dystonia. On the whole, 15 patients were affected by AEs and seven patients suspended RTG treatment due to AEs. The results show that transdermal RTG is effective with a good tolerability profile. RTG patch could be a good therapeutic tool in patients with APS.

Behavioral and neurophysiological effects of transdermal rotigotine in atypical parkinsonism.

Effective therapies for the so-called atypical parkinsonian syndrome (APS) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome (CBS) are not available. Dopamine agonists (DA) are not often used in APS because of inefficacy and in a minority of case, their side effects, like dyskinesias, impairment of extrapyramidal symptoms or the appearance of psychosis, and REM sleep behavioral disorders (RBD). Transdermal rotigotine (RTG) is a non-ergot dopamine agonist indicated for use in early and advanced Parkinson's disease with a good tolerability and safety. Moreover, its action on a wide range of dopamine receptors, D1, D2, D3, unlike other DA, could make it a good option in APS, where a massive dopamine cell loss is documented. In this pilot, observational open-label study we evaluate the efficacy and tolerability of RTG in patients affected by APS. Thirty-two subjects with diagnosis of APS were treated with transdermal RTG. APS diagnosis was: MSA parkinsonian type (MSA-P), MSA cerebellar type (MSA-C), PSP, and CBS. Patients were evaluated by UPDRS-III, neuropsychiatric inventory, mini mental state examination at baseline, and after 6, 12, and 18 months. The titration schedule was maintained very flexible, searching the major clinical effect and the minor possible adverse events (AEs) at each visit. AEs were recorded. APS patients treated with RTG show an overall decrease of UPDRS-III scores without increasing behavioral disturbances. Only three patients were dropped out of the study. Main AEs were hypotension, nausea, vomiting, drowsiness, and tachycardia. The electroencephalographic recording power spectra analysis shows a decrease of theta and an increase of low alpha power. In conclusion, transdermal RTG seems to be effective and well tolerated in APS patients.