Elevated caudate connectivity in cognitively normal Parkinson's disease patients.

Mild cognitive impairment (MCI) is common in Parkinson's disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson's patients. We recruited 18 Parkinson's disease patients-10 PDNC [normal cognition Parkinson's disease; Montreal Cognitive Assessment (MoCA) ≥ 26], 8 PDLC (low cognition Parkinson's disease; MoCA < 26) -and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer's disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson's patient groups, but not in healthy control subjects. Interestingly, PDNC's functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer's disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson's disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson's disease. Our findings support and complement the dual syndrome hypothesis.

Orthostatic hypotension and dementia incidence: links and implications.

Orthostatic hypotension (OH) is a common condition, particularly in patients with α-synucleinopathies such as Parkinson's disease, and has a significant impact on activities of daily living and quality of life. Recent data suggest an association with cognitive impairment. Herein, we review the evidence that OH increases the odds of incident mild cognitive impairment and dementia. Potential mechanisms underlying the putative relationship are discussed, including cerebral hypoperfusion, supine hypertension, white matter hyperintensities, and neurodegeneration. Finally, we highlight the challenges with respect to treatment and the negative impact on the quality of life and long-term prognosis presented by the coexistence of OH and dementia. Large population-based studies have reported that OH is associated with about a 20% increased risk of dementia in the general population, while smaller cohort studies suggest an even greater effect in patients with α-synucleinopathies (3- to 7-fold higher than controls). Ultimately, OH exposure is difficult to quantify, predominantly limited to pressure regulation during a one-time orthostatic challenge, and the causative association with dementia may turn out to be bidirectional, especially in α-synucleinopathies. Early diagnosis and treatment of OH may improve long-term prognosis.

Educational Needs and Considerations for a Visual Educational Tool to Discuss Parkinson's Disease.

BACKGROUND: In our clinical experience, people with Parkinson's disease (PwP) and their caregivers have difficulty understanding the complexities of the disease, which has a multitude of symptoms and involved therapies. We undertook a needs assessment to understand the need for, and to guide the development of, an educational tool. METHODS: We invited PwP, caregivers and health care providers (HCP) from across Canada to participate in an online survey to determine the need and desired content for such a tool. RESULTS: Respondents included 450 PwP, 335 caregivers, and 96 HCP from across Canada. 86.5% of HCP reported that it was "very important" for patients to understand issues in PD and 84.4% would use a visual aid to explain these issues. Results showed that 81.9-95.7% of caregivers and PwP were not "very satisfied" with the explanations of all domains in PD. Non-motor symptoms and cognitive issues were highly ranked by all groups as difficult to understand or explain. Older PwP (those with PD for less than 5 years and those who reported that their HCP spent less than 15 minutes counselling in each clinic visit) were less likely to fully understand and be satisfied with the explanations of most issues in PD. INTERPRETATION: There is a need for better patient education when discussing PD issues in the clinical setting. Older PwP that have been recently diagnosed have the greatest educational needs. Potential users indicate that a visual aid would help and non-motor symptoms, particularly cognitive issues, need to be a focus of such a tool.

Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2.

OBJECTIVE: To delineate the natural history, diagnosis, and treatment response of Parkinson disease (PD) in individuals with 22q11.2 deletion syndrome (22q11.2DS), and to determine if these patients differ from those with idiopathic PD. METHODS: In this international observational study, we characterized the clinical and neuroimaging features of 45 individuals with 22q11.2DS and PD (mean follow-up 7.5 ± 4.1 years). RESULTS: 22q11.2DS PD had a typical male excess (32 male, 71.1%), presentation and progression of hallmark motor symptoms, reduced striatal dopamine transporter binding with molecular imaging, and initial positive response to levodopa (93.3%). Mean age at motor symptom onset was relatively young (39.5 ± 8.5 years); 71.4% of cases had early-onset PD (<45 years). Despite having a similar age at onset, the diagnosis of PD was delayed in patients with a history of antipsychotic treatment compared with antipsychotic-naive patients (median 5 vs 1 year, p = 0.001). Preexisting psychotic disorders (24.5%) and mood or anxiety disorders (31.1%) were common, as were early dystonia (19.4%) and a history of seizures (33.3%). CONCLUSIONS: Major clinical characteristics and response to standard treatments appear comparable in 22q11.2DS-associated PD to those in idiopathic PD, although the average age at onset is earlier. Importantly, treatment of preexisting psychotic illness may delay diagnosis of PD in 22q11.DS patients. An index of suspicion and vigilance for complex comorbidity may assist in identifying patients to prioritize for genetic testing.

'Under pressure': is there a link between orthostatic hypotension and cognitive impairment in α-synucleinopathies?

Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are characterised by abnormal neuroglial α-synuclein accumulation. These α-synucleinopathies have in common parkinsonism and non-motor features including orthostatic hypotension (OH) and cognitive impairment. However, the nature of the relationship between OH and cognitive impairment is unclear. We therefore systematically reviewed the literature for evidence of an association between OH and cognitive impairment in α-synucleinopathies and discuss possible mechanisms and implications of this relationship. Abstracts from 313 original research articles were surveyed, and a total of 132 articles were considered for this review. Articles were stratified as: 'direct-evidence studies' based on the direct assessment for a relationship between OH and cognitive impairment in α-synucleinopathies, and 'indirect-evidence studies' based on an association being referred to as a secondary outcome. Ten 'direct-evidence papers' were identified, seven of which reported a positive association between OH and cognitive impairment, while seven of 12 'indirect-evidence papers' similarly did as well. The papers that reported no association between OH and cognitive impairment used less sensitive measures of cognition. A relationship between OH and cognitive impairment in patients with α-synucleinopathies exists, but the underlying mechanisms remain unclear. Three hypotheses are proposed: (1) OH and cognitive impairment occur concurrently due to diffuse brain and peripheral deposition of α-synuclein, (2) OH-mediated cerebral hypoperfusion impairs cognition and (3) the two act synergistically to accelerate cognitive decline. Longitudinal neuroimaging studies and clinical trials may help clarify the nature of this relationship.

Clinical features of dog- and bat-acquired rabies in humans.

BACKGROUND: Clinical differences in rabies due to canine and bat rabies virus variants have been noted, but no detailed studies have been reported to support these observations. METHODS: Using the Morbidity and Mortality Weekly Report and PubMed, we identified 142 case reports of rabies from North America, South America, Europe, Africa, and Asia. We systematically abstracted 126 selected data elements and compared clinical features and investigation results in dog- and bat-acquired cases of rabies. RESULTS: Survivors and cases acquired from aerosolized viral exposure or tissue/organ transplant were excluded (n = 20). Of 122 cases, 49 (40.2%) were dog-acquired and 54 (44.3%) were bat-acquired. Bat-acquired cases of rabies were more often misdiagnosed and lacked a bite history. Encephalopathy, hydrophobia, and aerophobia were more common in dog-acquired rabies. Abnormal cranial nerve, motor, and sensory examinations, tremor, myoclonus, local sensory symptoms, symptoms at the exposure site, and local symptoms in the absence of a bite or scratch were more common in patients with bat-acquired rabies, as was increased cerebrospinal fluid protein (P = .031). Patients with paralytic rabies had longer survival times than those with encephalitic rabies, and also had shorter incubation periods if they had received postexposure prophylaxis. CONCLUSIONS: Clinical differences in dog- and bat-acquired rabies may reflect differences in the route of viral spread of rabies virus variants in the nervous system, although certain variants could cause more severe dysfunction in neuronal subpopulations. Recognition that bat-acquired rabies may present with different clinical manifestations than dog-acquired rabies may help improve the early diagnosis of rabies.

Prolonged survival and serial magnetic resonance imaging/magnetic resonance spectroscopy changes in infantile Krabbe disease.

Krabbe disease may present during infancy, late infancy, or adulthood. Earlier-onset disease is associated with shorter survival times. We present a case of infantile onset Krabbe disease with prolonged survival, initial intracranial optic nerves and optic chiasm hypertrophy, and serial changes on cranial magnetic resonance imaging and magnetic resonance spectroscopy.