Mortality and causes of death in patients with Parkinson's disease: a nationwide population-based cohort study.

Objective: Parkinson's disease (PD) is a neurodegenerative disease involving multiple systems that can affect mortality. This study aimed to compare all-cause and cause-specific mortality between people with PD and without PD. Methods: This population-based prospective cohort study is based on Korean National Health Insurance Service data. The primary outcome was the hazard ratio (HR) of all-cause and cause-specific mortality for PD from 2010 to 2019. Cox proportional hazards regression was applied to calculate HRs under crude and three adjusted models with epidemiologic variables. Results: A total of 8,220 PD patients and 41,100 age- and sex-matched controls without PD were registered. Ten-year mortality was 47.9% in PD patients and 20.3% in non-PD controls. The mortality rate was higher among older and male participants. The leading cause of death in PD was nervous system diseases (38.73%), and 97.1% of those were extrapyramidal and movement disorders, followed by circulatory diseases (15.33%), respiratory diseases (12.56%), and neoplasms (9.7%). PD contributed to an increased risk of all-cause death with an HR of 2.96 (95% CI = 2.84-3.08). HRs of death for PD were 3.07 (95% CI = 2.74-3.45) from respiratory diseases, 1.93 (95% CI = 1.75-2.13) from circulatory diseases, 2.35 (95% CI = 2.00-2.77) from external causes, and 2.69 (95% CI = 2.10-3.43) from infectious diseases. Conclusion: These results showed that PD was related to a higher risk of mortality in all ages and sexes. The leading causes of death in PD were nervous, circulatory, respiratory, infectious diseases, and external causes.

Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data.

BACKGROUND AND PURPOSE: Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer's disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. METHODS: We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. RESULTS: Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18-9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. CONCLUSIONS: Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

Dynamic Changes of Carotid Atherosclerosis and Their Relation with Stroke Recurrence in Patients with Stroke or Transient Ischemic Attack.

BACKGROUND AND PURPOSE: The purpose of this study was to show dynamic changes in carotid and vertebral artery using carotid Doppler ultrasonography (DUS) through a long-term follow- up exam, and determine their associations with stroke recurrence. METHODS: We consecutively enrolled stroke or transient ischemic attack (TIA) patients who had undergone DUS more than twice with intervals of three months or more. Stroke recurrence during follow-up was also investigated by reviewing medical records. Progress or regress of plaque was defined as more than 0.1 mm change from the initial scan with a semi-quantitative measurement. The development of new plaque was also regarded as plaque progress. Increased intima-media thickness and plaque presence were interpreted at the initial and follow-up scans. Factors related to progression or regression were analyzed. The relationship between plaque change and stroke recurrence was investigated. RESULTS: A total of 201 patients were enrolled (186 ischemic stroke patients and 15 TIA patients). There were 61 (30.3%) females. Their mean age was 64.2 ± 9.9 years. During a follow-up of 35.0 ± 22.6 (mean ± SD) months, plaque progress was observed in 92 (45.8%) and plaque regress in 13 (6.5%). Stroke recurred in 18 patients. Plaque progression showed no significant association with age, risk factors, statin use, or subtype. After adjustment of age, sex, diabetes, and stroke subtype, multiple logistic regression showed a significant association of plaque progression with stroke recurrence (odds ratio: 3.8, 95% confidence interval: 1.1 to 13.1, p = 0.034). Patients with plaque regress were significantly younger than those without plaque regress (57.8 years vs. 64.6 years, p = 0.041). CONCLUSION: Plaque progression occurred in 46% of stroke or TIA patients. Plaque progression was significantly associated with clinical stroke recurrence. Plaque regressed in 6.5% of patients. Patients with regression were younger than those without.

Newly diagnosed diabetes has high risk for cardiovascular outcome in ischemic stroke patients.

We investigated cardiovascular outcomes in ischemic stroke patients with newly diagnosed diabetes mellitus (DM) compared with those of patients with previously known DM and no DM using the glycosylated hemoglobin (HbA1c) criteria. The relationship between new DM diagnosis and cardiovascular risk remains unclear to date. We performed post hoc analysis using the data of participants from the Prevention of Cardiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO) trial. Newly diagnosed DM was defined as HbA1c of ≥ 6.5% without known DM history. The outcome was the incidence of composite cardiovascular events, including stroke (ischemic and hemorrhagic), myocardial infarction, and cardiovascular death. In total, 1306 patients were included; 38 patients (2.9%) had newly diagnosed DM; 438 patients (33.5%), known DM; and 830 patients (63.6%), no DM. In patients with newly diagnosed DM, known DM, and no DM, the incidence of ischemic stroke was 8.93, 3.79, and 2.64 per 100 person-years (log-rank test; p = 0.0092), while that of composite cardiovascular events was 8.93, 5.92, and 3.87 per 100 person-years (p = 0.025), respectively. Newly diagnosed DM was an important risk factor for ischemic stroke and composite cardiovascular events after ischemic stroke.Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01013532.

Differentiation of hemorrhagic infarction from primary intracerebral hemorrhage in the chronic period.

Regarding incidentally found old hemorrhagic foci on gradient-echo magnetic resonance imaging (GRE), it is difficult to distinguish whether the foci are the consequence of hemorrhagic infarction (HI) or primary intracerebral hemorrhage (PICH). We analyzed the radiological characteristics of patients with a definite history of HI or PICH by reviewing long-term follow-up GRE. We retrospectively enrolled patients with HI or PICH, verified by clinical history and radiological findings, who had undergone follow-up GRE at least 3 months after the first imaging. The shape of the hemorrhagic lesion was classified as "cavitation" or "no cavitation." The shape of the hemosiderin rim was classified as total dark rim and partial dark rim. Hyperintense perilesional signal was determined when an obvious hyperintensity on T2-weighted image was present. Further, we compared the radiological characteristics between HI and PICH. In total, 69 patients (38 with HI and 31 with PICH) were enrolled, of whom 45 (65%) were men. The mean patient age was 65.5 ± 12.7 years. The mean time interval from the initial stroke onset to the follow-up image was 56.2 months. Hyperintense perilesional signal was observed in 38 patients; it was associated with HI (33/38 vs. 5/31, p < 0.001). Furthermore, partial dark rim was associated with HI (34/40 vs. 4/29, p < 0.001). Cavitation was more frequently observed in patients with HI than in those with PICH (36/60 vs. 2/9, p = 0.068). Presence of hyperintense perilesional signal and partially encasing dark hemosiderin rim suggest that chronic hemorrhagic foci are the sequelae of HI, not PICH.

Coexistence of Cerebral Microbleeds and Amyloid Pathology in Patients with Cognitive Complaints.

BACKGROUND AND PURPOSE: We investigated the prevalence of amyloid positivity and cerebral microbleeds (CMBs) in subjects with cognitive complaints with the aim of identifying differences in clinical parameters and cognitive function according to the pattern of coexistence. METHODS: We retrospectively enrolled 200 subjects with memory impairment and applied both standardized ¹8F-florbetaben PET and brain MRI, including susceptibility-weighted imaging. The amyloid burden was visually classified as positive or negative, and the number and location of CMBs were also analyzed visually. Descriptive analysis was performed for the prevalence of amyloid positivity and CMBs. The relationship between the coexisting pattern of those two findings and clinical parameters including the results of neuropsychiatric tests was analyzed. RESULTS: Positive amyloid PET scans were exhibited by 102 (51.5%) of the 200 patients, and 51 (25.5%) of them had CMBs, which were mostly located in lobar areas in the patients with positive amyloid scans. The patients with CMBs were older and had a higher burden of white-matter hyperintensities than the patients without CMBs. The patients with CMBs also performed worse in confrontation naming and frontal/executive function. When classified by topographical region, parietal CMBs (odds ratio=3.739, p=0.024) were significantly associated with amyloid positivity. CONCLUSIONS: The prevalence of CMBs was higher in patients with cognitive decline than in the general population. CMBs play distinctive roles in affecting clinical parameters and neuropsychological profiles according to the coexistence of amyloid pathology.

Early Functional Connectivity Predicts Recovery from Visual Field Defects after Stroke.

BACKGROUND AND PURPOSE: We aimed to assess whether early resting-state functional connectivity (RSFC) changes measured via functional magnetic resonance imaging (fMRI) could predict recovery from visual field defect (VFD) in acute stroke patients. METHODS: Patients with VFD due to acute ischemic stroke in the visual cortex and age-matched healthy controls were prospectively enrolled. Serial resting-state (RS)-fMRI and Humphrey visual field (VF) tests were performed within 1 week and at 1 and 3 months (additional VF test at 6 months) after stroke onset in the patient group. The control group also underwent RS-fMRI and a Humphrey VF test. The changes in RSFCs and VF scores (VFSs) over time and their correlations were investigated. RESULTS: In 32 patients (65±10 years, 25 men), the VFSs were lower and the interhemispheric RSFC in the visual cortices was decreased compared to the control group (n=15, 62±6 years, seven men). The VFSs and interhemispheric RSFC in the visual cortex increased mainly within the first month after stroke onset. The interhemispheric RSFC and VFSs were positively correlated at 1 month after stroke onset. Moreover, the interhemispheric RSFCs in the visual cortex within 1 week were positively correlated with the follow-up VFSs. CONCLUSIONS: Interhemispheric RSFCs in the visual cortices within 1 week after stroke onset may be a useful biomarker to predict long-term VFD recovery.

Evolution of acute lacunar lesions in terms of size and shape: a PICASSO sub-study.

The imaging definition of lacunar infarcts is variable, particularly regarding their size and the presence of cavitation. We investigated the changes of diameter and evolution pattern of acute lacunar infarcts, and the factors associated with the evolution pattern. Patients with acute single subcortical hemispheric or brainstem ischemic lesions of penetrating arterial territories were included. Maximal diameters on initial diffusion-weighted image (DWI) and follow-up fluid-attenuated inversion recovery image (FLAIR), which performed > 12 months after initial DWI, were semi-automatically measured. Clinical characteristics were compared according to evolution patterns on follow-up FLAIR, classified as cavitated, focal lesion without cavitation, and disappeared. Five hundred nine patients were included. Mean time to follow-up was 31.3 ± 13.7 months. Mean diameter of acute lacunar lesions decreased from 12.9 ± 4.4 to 8.5 ± 4.8 mm during follow-up. Lesions of 58.2% patients remained as cavitated, 18.3% as focal lesion without cavitation, and 23.6% disappeared. Initial NIHSS score (p = 0.005), diameter of initial lesion (p < 0.001), number of slices showing acute lesion on DWI (p < 0.001), progression of white matter lesion (p < 0.001), number of acute lesions involving gray matter (p = 0.008) and lesion location (p < 0.001) were different among three groups. After adjustment for covariates, diameter of the acute lesion, initial number of old lacunes, and anterior lesion location were associated with the appearance of cavitation. Initial lesion diameter and posterior lesion location were associated with the disappearance. We observed reduction of the acute lacunar lesion diameter in 86%. There were predictive factors of disappearance and cavitation of acute lacunar infarction.

Different Cortical Thinning Patterns Depending on Their Prognosis in Individuals with Subjective Cognitive Decline.

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) may be the first stage corresponding to subtle cognitive changes in patients with Alzheimer's disease (AD) spectrum disorders. We evaluated the differences in cortical thinning patterns among patients with SCD who progressed to mild cognitive impairment or dementia (pSCD), those who remained stable (sSCD), and healthy normal controls (NCs). METHODS: We retrospectively recruited SCD subjects (14 pSCD and 21 sSCD cases) and 29 NCs. Structural 3-dimensional-T1-weighted magnetic resonance imaging was performed using a single 1.5 Tesla scanner. Freesurfer software was used to map cortical thickness for group comparisons. RESULTS: Compared with NC group, the sSCD group showed diffuse cortical atrophy associated with bilateral fronto-parieto-temporal area. The pSCD group showed further characteristic cortical atrophy in AD-vulnerable regions including the inferior parieto-temporal and middle temporal areas. Cortical thinning in the bilateral medial frontal areas was observed in patients with sSCD and involved the right inferior temporal and left precentral areas in those with pSCD. CONCLUSIONS: Our study showed that SCD subjects exhibit different cortical thinning patterns depending on their prognosis.

Cerebral Microbleeds in a Stroke Prevention Clinic.

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores <300 cm3 at both baseline (12.6 ± 11.7 vs. 4.9 ± 2.2, p = 0.02) and follow-up (14.1 ± 11.8 vs. 5.6 ± 2.4, p = 0.03) MRI evaluations. Patients with CMB had a relatively benign overall clinical course. The association between CMB burden and intracranial calcification warrants further study.

Cerebrovascular Hemodynamics on Transcranial Doppler Ultrasonography and Cognitive Decline in Mild Cognitive Impairment.

BACKGROUND/OBJECTIVE: Vascular risk factors and neurovascular dysfunction may be closely related to cognitive impairment and dementia. In this study, we evaluated the association between hemodynamic markers and longitudinal cognitive changes in patients with mild cognitive impairment (MCI). Furthermore, we investigated whether hemodynamic markers could predict the risk of progression to Alzheimer's disease (AD) in patients with MCI. METHODS: A total of 68 subjects with amnestic MCI were recruited. Using transcranial Doppler (TCD) ultrasonography, cerebrovascular reactivity was evaluated with a breath-holding test (breath holding index; BHI) in addition to the mean flow velocity (MFV) and pulsatility index (PI) of the middle cerebral artery. We followed subjects for 24 months and each subject underwent neuropsychological testing and TCD ultrasonography, annually. According to the follow-up neuropsychological studies and clinical interviews at 12 months, we divided the patients with MCI into two groups: patients with stable cognitive performance and patients who progressed to AD. RESULTS: Lower BHI and higher PI were observed in patients who progressed to AD. The changes of MMSE score over the first 12 months correlated with lower baseline MMSE score and changes of MFV and BHI. The changes of MMSE score over 24 months were closely related to higher baseline resistance index and PI values. Multivariate logistic regression showed that abnormal baseline BHI value could predict a conversion from MCI to AD. CONCLUSIONS: We confirmed there is a close association between hemodynamic changes represented by TCD markers and cognitive decline, supporting the clinical value of hemodynamic markers in predicting MCI patients who will progress to AD.

Safety and Efficacy of Anti-dementia Agents in the Extremely Elderly Patients with Dementia.

BACKGROUND: There are debates on representation and generalizability of previous randomized controlled trials about anti-dementia agents in the oldest old population. In this context, we aimed to investigate the efficacy and safety of anti-dementia agents in the very elderly patients with dementia. METHODS: We conducted a retrospective study of patients with dementia 1) who were 85 years or older, 2) got started anti-dementia agents, and 3) went through follow-up evaluation about one year thereafter. As a control, patients with dementia who were less than 85 years old with similar inclusion criteria were randomly selected during the same period. The adverse drug effects and discontinuation rates were investigated with self-reported complaint after starting or increasing anti-dementia drugs. For efficacy outcome, we also analyzed the change in neuropsychological results during follow-up period. RESULTS: A total of 77 dementia patients who were at least 85 years were enrolled. As a control group, 78 patients with dementia who were younger than 85 was analyzed. The adverse drug effects were observed in 26 (33.3%) patients in the younger old and in 26 (33.8%) in the oldest old (P = 0.095). Twenty-one patients (26.9%) in the younger old group and 13 patients (16.9%) in the oldest old group discontinued their medication (P = 0.131). There were no differences between the two groups about changes of Mini-Mental State Examination and Instrumental Activity of Daily Living scores over time. CONCLUSION: The use of anti-dementia agents in the oldest old dementia patients may be safe and effective as the younger old dementia patients.

The Fate of Acute Lacunar Lesions in Terms of Shape and Size.

BACKGROUND: The description of lacunar infarcts on imaging is widely variable. In particular, there are fewer agreements on lacunar lesion size and the presence of cavitation. In this regard, we investigated the changes in size and shape of acute ischemic lesion that is possibly considered as small vessel occlusion on long-term follow-up. METHODS: Patients with acute single subcortical ischemic lesion on penetrating arterial territories and without definite cause of cardioembolism and large vessel disease were included. Magnetic resonance imaging (MRI) was performed during an acute stroke period and approximately 1 year after the stroke. Maximal diameters on diffusion-weighted image and on follow-up (T2 or fluid attenuation inversion recovery) were measured. The change in lesion diameter over time was analyzed. Regarding the change in shape, lacunar lesions on follow-up were classified as either "disappeared," "cavitated," or "white matter lesion." RESULTS: A total of 64 patients were included. The mean age was 64.94 ± 11.29 years and 32 patients were male. The mean time interval between initial and follow-up MR scan was 23.39 ± 14.88 months. The mean diameter of acute lacunar lesion was 14.11 ± 5.77 mm. On follow-up, the mean diameter reduced to 7.76 ± 5.19 mm. The mean percentage of final diameter over initial diameter was 53.57 ± 26.45%. All of the lesions were less than 15 mm on follow-up. Regarding the shape of the lesion on follow-up, the lesions of 33 (51.6%) patients remained cavitated, the lesions of 14 (21.9%) patients remained as white matter lesions, and the lesions of 17 (26.6%) patients disappeared. There were no differences on clinical characteristics between patients with cavitation and those without. CONCLUSIONS: The diameter of acute lacunar lesions on initial diffusion-weighted MRI was markedly reduced on follow-up. In 52% of the patients, acute lacunar lesions were cavitated.

Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: Data from a nationwide registry in Korea.

We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause.

Previous and Recent Evidence of Endovascular Therapy in Acute Ischemic Stroke.

The ideal therapy of acute ischemic stroke is achieved by early recanalization that finally leads to good clinical outcome. The recombinant intravenous tissue plasminogen activator (rtPA) within 4.5 hours was approved as an important thrombolytic treatment. However, the recanalization rate was low in patients with a large artery occlusion. The efficacy of intravenous rtPA regarding recanalization of a large artery occlusion was limited. In several clinical trials, pharmacological and mechanical intra-arterial thrombolytic therapy showed improved recanalization rates, but the favorable outcome had not been achieved. Through those trials and errors, researchers have learned that speed of treatment initiation, patient selection by documentation of large artery occlusion and the use of effective devices could be crucial for good clinical outcomes. Finally, five recent randomized controlled trials of endovascular therapy compared to standard medical care have been published. The superiority of endovascular thrombolysis to standard medical care was proved. In this article, we reviewed previous and recent clinical evidence about endovascular thrombolytic therapy of acute ischemic stroke.

Readout-segmented echo-planar imaging in diffusion-weighted MR imaging of acute infarction of the brainstem and posterior fossa: comparison of single-shot echo-planar diffusion-weighted sequences.

OBJECTIVE: The purpose of this study was to evaluate the clinical usefulness of readout-segmented echo-planar imaging (rs-EPI) in the diagnosis of acute infarction of the brainstem and posterior fossa, by comparing its results with those of single-shot echo-planar imaging (ss-EPI) at 3-T magnetic resonance imaging. MATERIALS AND METHODS: Twenty-nine patients with acute infarctions of the brainstem and posterior fossa underwent both ss-EPI and rs-EPI. Two readers independently assessed two sets of diffusion-weighted (DW) images for the qualitative comparison of image quality. Signal-to-noise ratio (SNR), lesion contrast, and contrast-to-noise ratio (CNR) were calculated for the assessment of image parameters. RESULTS: There were no significant differences in the conspicuity of acute infarction upon qualitative comparison; however, distinctions of anatomical structures, susceptibility artifact, the presence of uncertain high signal intensity in the brain parenchyma, and overall image quality were significantly better in rs-EPI DW images. There were no significant differences in SNR, lesion contrast, CNR, and apparent diffusion coefficient values of acute infarction and normal thalamus between rs-EPI and ss-EPI. CONCLUSION: rs-EPI DWI is a clinically useful technique for evaluating lesions in the brainstem and posterior fossa by producing high-resolution DW images with reduced susceptibility artifact. However, there are no significant differences in the conspicuity of acute infarctions in the brainstem and posterior fossa between rs-EPI and ss-EPI.