Identifying subtypes of mild cognitive impairment in Parkinson’s disease using cluster analysis

Journal of Neurology - The concept of Mild Cognitive Impairment (MCI) in Parkinson’s disease (PD) has shown the potential for identifying at-risk dementia patients. Identifying subtypes of...     

Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson’s disease

Journal of Neurology - Cognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been...     

Widespread cortical and subcortical brain atrophy in Parkinson’s disease with excessive daytime sleepiness

Our aim was to determine regional brain atrophy in Parkinson’s disease (PD) patients with excessive daytime sleepiness (EDS) using voxel-based morphometry (VBM). From 71 consecutive probable PD patients, nine non-demented and non-hallucinating patients with an Epworth Sleepiness Scale (ESS) ≥ 10 and 13 PD patients with an ESS ≤ 3 were selected as having EDS and as not having EDS, respectively. We also enrolled 22 healthy age- and sex-matched controls. Regional brain atrophy was assessed using VBM with 3-T magnetic resonance imaging. There was no difference in the dosage of dopaminergic drugs between PD patients with EDS and PD patients without EDS. PD patients with EDS showed marked atrophy in the gray matter of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to controls (false discovery rate corrected p < 0.05). In contrast, PD patients without EDS did not show any significant difference in gray matter atrophy compared to controls (false discovery rate corrected p < 0.05). PD patients with EDS showed significant atrophy of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to PD patients without EDS (uncorrected p < 0.001). PD patients with EDS, even without dementia and hallucination, showed significant gray matter atrophy compared to PD patients without EDS and controls.     

Long-term cognitive outcome of bilateral subthalamic deep brain stimulation in Parkinson’s disease

The effect of subthalamic deep brain stimulation (STN DBS) on cognition in Parkinson’s disease (PD) remains controversial, and it is unclear which factors are related to cognitive decline and dementia after STN DBS, especially over the long term. To this end, we analyzed the cognitive outcome of 103 non-demented patients with PD who were followed-up for at least 12 months after bilateral STN DBS surgery. Preoperatively, the patients were evaluated with the Unified Parkinson's Disease Rating Scale and neuropsychological tests. The rate of global cognitive decline and the incidence of dementia during follow-up for up to 7 years (mean 42.4 ± 24.5 months) were calculated, and preoperative clinical and neuropsychological factors associated with postoperative global cognitive decline or dementia were analyzed. The prevalence of mild cognitive impairment (MCI) and its relation to later cognitive decline or dementia were also evaluated. The annual decline in the mini–mental state examination score was 0.4 ± 1.7 with impaired attention and executive function and a higher levodopa equivalent dose at baseline being the predictors of a faster global cognitive decline after STN DBS. Dementia developed in 13 patients with an incidence rate of 35.7 per 1,000 person-years. Impaired executive function at baseline predicted dementia. At baseline, 63.1 % of the patients had PD-MCI, and these patients were more likely to develop dementia than those without PD-MCI. This study showed that dysfunctions in the frontostriatal circuitry at baseline were associated with a risk of subsequent global cognitive decline and dementia in patients with PD who underwent STN DBS. In addition, preoperative PD-MCI was a risk factor for dementia after STN DBS.     

The exploration of Parkinson’s disease: a multi-modal data analysis of resting functional magnetic resonance imaging and gene data

Parkinson’s disease (PD) is the most universal chronic degenerative neurological dyskinesia and an important threat to elderly health. At present, the researches of PD are mainly based on single-modal data analysis, while the fusion research of multi-modal data may provide more meaningful information in the aspect of comprehending the pathogenesis of PD. In this paper, 104 samples having resting functional magnetic resonance imaging (rfMRI) and gene data are from Parkinson’s Progression Markers Initiative (PPMI) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to predict pathological brain areas and risk genes related to PD. In the experiment, Pearson correlation analysis is adopted to conduct fusion analysis from the data of genes and brain areas as multi-modal sample characteristics, and the clustering evolution random forest (CERF) method is applied to detect the discriminative genes and brain areas. The experimental results indicate that compared with several existing advanced methods, the CERF method can further improve the diagnosis of PD and healthy control, and can achieve a significant effect. More importantly, we find that there are some interesting associations between brain areas and genes in PD patients. Based on these associations, we notice that PD-related brain areas include angular gyrus, thalamus, posterior cingulate gyrus and paracentral lobule, and risk genes mainly include C6orf10, HLA-DPB1 and HLA-DOA. These discoveries have a significant contribution to the early prevention and clinical treatments of PD.

     

Supine hypertension in Parkinson’s disease and multiple system atrophy

Objective

Supine hypertension (SH) is a feature of cardiovascular autonomic failure that often accompanies orthostatic hypotension and may represent a negative prognostic factor in parkinsonian syndromes. Here we investigated the frequency rate as well as the clinical and tilt test correlates of SH in Parkinson’s disease (PD) and multiple system atrophy (MSA).

Methods

197 PD (33 demented) and 78 MSA (24 MSA-Cerebellar, 54 MSA-Parkinsonian) patients who had undergone a tilt test examination were retrospectively included. Clinical-demographic characteristics were collected from clinical records at the time of the tilt test examination.

Results

SH (>140 mmHg systolic, >90 mmHg diastolic) occurred in 34 % of PD patients (n = 66, mild in 71 % of patients, moderate in 27 %, severe in 2 %) and 37 % of MSA ones (n = 29, mild in 55 % of patients, moderate in 17 %, severe in 28 %). No difference was observed in SH frequency between demented versus gender-, age- and disease duration-matched non-demented PD patients, or between patients with the parkinsonian (MSA-P) versus the cerebellar (MSA-C) variant of MSA. In PD, SH was associated with presence of cardiovascular comorbidities (p = 0.002) and greater systolic (p = 0.007) and diastolic (p = 0.002) orthostatic blood pressure fall. Orthostatic hypotension (p = 0.002), and to a lesser degree, lower daily dopaminergic intake (p = 0.01) and use of anti-hypertensive medications (p = 0.04) were associated with SH in MSA.

Interpretation

One-third of PD and MSA patients suffer from mild to severe SH, independently of age, disease duration or stage. In PD, cardiovascular comorbidities significantly contribute to the development of SH, while in MSA, SH appears to reflect cardiovascular autonomic failure.

     

Profiling cognitive and neuropsychiatric heterogeneity in Parkinson’s disease

BackgroundParkinson’s disease (PD) is a highly heterogeneous disease, in which motor symptom subtypes are often-described. While it is recognized that motor, cognitive and affective neuropsychiatric symptoms negatively influence the patients’ quality of life, it is currently unknown how these symptoms contribute to phenotypic subtypes. The objective of this study was to assess subtypes of motor, cognitive and affective symptoms in PD.MethodsA hierarchical cluster analysis was conducted on clinical data of 226 PD patients screened at the VU University Medical Center using comprehensive assessment of cognitive, affective and motor symptoms. Subsequent linear discriminant analyses were conducted to investigate discriminating constructs between clusters.ResultsThe cluster analysis yielded four clusters: (1) a young-age (59.9 years), mildly affected cluster (N = 86), (2) an old-age (72.3 years) cluster with severe motor and non-motor symptoms (N = 15), (3) a cluster (age 64.7 years) with mild motor symptoms, below-average executive functioning and affective symptoms (N = 46) and (4) a cluster (age 64.8 years) with severe motor symptoms, affective symptoms and below-average verbal memory (N = 79).ConclusionsCluster 1 and 2 seem to represent opposite ends of the PD disease stages. Patients in clusters 3 and 4 had similar age, educational level and disease duration but different symptom profiles – we therefore suggest that these clusters represent different pathways of disease progression, presumably with distinct underlying pathology localization. Future research on the neuropathophysiological characteristics of these two clusters and monitoring of disease progression is required.     

Characterization of gait variability in multiple system atrophy and Parkinson’s disease

Journal of Neurology - Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. We compared...     

Automated brain volumetric program measuring regional brain atrophy in diagnosis of mild cognitive impairment and Alzheimer’s disease dementia

Brain Imaging and Behavior - A quantitative analysis of brain volume can assist in the&nbsp;diagnosis of Alzheimer’s disease (AD) which is&nbsp;ususally accompanied by brain atrophy....     

Mild cognitive impairment in Parkinson’s disease

Parkinson’s disease (PD) has initially been described as a clinical syndrome, although its exact definition has changed over the past centuries. The identification of the pathological changes added another level of complexity, with Lewy bodies, synuclein deposits and neuronal loss in the substantia nigra being used alternatively as criteria. A third level of complexity was added with the recognition of genetic mutations resulting in Parkinsonism, sometimes with and sometimes without Lewy bodies or synuclein deposition. Lastly, frequent additional important pre-motor manifestations, particularly depression, anosmia and sleep-associated phenomena have been described. These different points of view on the definition of PD have important implications on the study of the etiology and even the therapy of PD. Cognitive impairment is also an important feature of PD, while the spectrum of deficits ranges from none to severe dementia. The no-man land in-between normal cognition and dementia has been termed mild cognitive impairment in PD. At present, this term lacks heuristic value or clinical utility, and remains a target for scientific research.     

Deep brain stimulation in Parkinson’s disease

Throughout the past decade, there has been a marked increase in surgical therapies, primarily deep brain stimulation (DBS), for the treatment of advanced Parkinson’s disease (PD). DBS of the thalamus has been shown to be effective in reducing parkinsonian tremor; however, it is not the treatment of choice for PD given the progression of other symptoms such as rigidity and bradykinesia. Stimulation of the globus pallidus or the subthalamic nucleus is safe and efficacious in the long-term treatment of all cardinal symptoms of PD, and they are currently the surgeries of choice. Serious adverse events with DBS can occur in 1% to 2% of patients, infection in 5% to 8% of patients, and hardware complications in approximately 25% of patients. Complications associated with DBS are related to the experience of the surgical center. Referring physicians and patients should be aware of the number of surgical procedures and complication rates of any prospective surgical center.     

Differences in cognitive performance in nondemented Parkinson’s disease: A latent profile analysis of cognitive subtypes

Introduction: Cognitive impairments are common in Parkinson’s disease (PD) patients without dementia. These deficits are quite heterogeneous, which makes it difficult to recognize and treat them. For this reason, many authors have attempted to classify patients into more homogeneous groups with diverse results. The present study was designed to analyze the cognitive heterogeneity in PD patients using a novel data-driven approach, latent profile analysis (LPA), to classify patients according to cognitive characteristics. This methodology, which has been used in previous studies focused on motor and psychiatric symptomatology, seems to be better than traditional cluster analysis for the establishment and comparison between different subgroups because it does not require prior decision making about some theoretical or methodological aspects.

Method: LPA was applied to 71 PD patients evaluated with a broad neuropsychological battery including different memory and executive function tests. The clusters obtained from the analysis were described by making comparisons with a control group of 51 healthy subjects matched in age, sex, and educational level.

Results: The LPA resulted in a four-cluster solution, which could be described as: (a) executive dysfunction (32.4%), (b) memory and executive dysfunction (28.2%), (c) memory dysfunction (23.9%), and (d) noncognitive dysfunction (15.5%). These four PD cluster differ in age and Mini-Mental State Examination (MMSE) score. However, there were no differences between clusters in disease duration, clinical impression of severity index, depression, and cognitive reserve.

Conclusions: LPA is a very interesting method for the establishment of more homogeneous groups of PD patients based on their neuropsychological characteristics. Moreover, the distinction between different cognitive profiles will allow us to design interventions better adapted to each patient.     

Do cognitive patterns of brain magnetic activity correlate with hippocampal atrophy in Alzheimer's disease?

BACKGROUND: Many reports support the clinical validity of volumetric MRI measurements in Alzheimer's disease. OBJECTIVE: To integrate functional brain imaging data derived from magnetoencephalography (MEG) and volumetric data in patients with Alzheimer's disease and in age matched controls. METHODS: MEG data were obtained in the context of a probe-letter memory task. Volumetric measurements were obtained for lateral and mesial temporal lobe regions. RESULTS: As expected, Alzheimer's disease patients showed greater hippocampal atrophy than controls bilaterally. MEG derived indices of the degree of activation in left parietal and temporal lobe areas, occurring after 400 ms from stimulus onset, correlated significantly with the relative volume of lateral and mesial temporal regions. In addition, the size of the right hippocampus accounted for a significant portion of the variance in cognitive scores independently of brain activity measures. CONCLUSIONS: These data support the view that there is a relation between hippocampal atrophy and the degree of neurophysiological activity in the left temporal lobe.     

Marked brain asymmetry with intact cognitive functioning in idiopathic Parkinson’s disease: a longitudinal analysis

Objective: A 71-year-old (MN) with an 11-year history of left onset tremor diagnosed as Parkinson’s disease (PD) completed longitudinal brain magnetic resonance imaging (MRI) and neuropsychological testing. MRI scans showed an asymmetric caudate nucleus (right < left volume). We describe this asymmetry at baseline and the progression over time relative to other subcortical gray, frontal white matter, and cortical gray matter regions of interest. Isolated structural changes are compared to MN’s cognitive profiles. Method: MN completed yearly MRIs and neuropsychological assessments. For comparison, left onset PD (n = 15) and non-PD (n = 43) peers completed the same baseline protocol. All MRI scans were processed with FreeSurfer and the FMRIB Software Library to analyze gray matter structures and frontal fractional anisotropy (FA) metrics. Processing speed, working memory, language, verbal memory, abstract reasoning, visuospatial, and motor functions were examined using reliable change methods. Results: At baseline, MN had striatal volume and frontal lobe thickness asymmetry relative to peers with mild prefrontal white matter FA asymmetry. Over time only MN’s right caudate nucleus showed accelerated atrophy. Cognitively, MN had slowed psychomotor speed and visuospatial-linked deficits with mild visuospatial working memory declines longitudinally. Conclusions: This is a unique report using normative neuroimaging and neuropsychology to describe an individual diagnosed with PD who had striking striatal asymmetry followed secondarily by cortical thickness asymmetry and possible frontal white matter asymmetry. His decline and variability in visual working memory could be linked to ongoing atrophy of his right caudate nucleus.     

Sex differences in brain atrophy and cognitive impairment in Parkinson’s disease patients with and without probable rapid eye movement sleep behavior disorder

Journal of Neurology - The presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson’s disease (PD), but the...