Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a ...coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.
Coronavirus disease 2019 (COVID‐19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory ...distress. Here, we described the case of a 60‐year‐old patient with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS‐CoV‐2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin‐8 and tumor necrosis factor‐α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high‐dose steroid treatment, thus arguing for an inflammatory‐mediated brain involvement related to COVID‐19. ANN NEUROL 2020;88:423–427.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Parkinson's disease (PD) is characterized by heterogeneity in clinical syndromes, prognosis, and pathophysiology mechanisms. Gender differences in neural anatomy and function are emerging as ...fundamental determinants of phenotypic variability. Different clinical subtypes, defined as mild motor predominant, intermediate, and diffuse-malignant, have been recently proposed in PD.
This study investigated gender influence on clinical features, dopaminergic dysfunction, and connectivity in patients with de novo idiopathic PD stratified according to the clinical criteria for subtypes (i.e., mild motor, intermediate, and diffuse-malignant). We included 286 drug-naïve patients (Males/Females: 189/97, age mean ± standard deviation: 61.99 ± 9.67; disease duration: 2.08 ± 2.21) with available 123IFP-CIT-SPECT and high-resolution T1-weighted MRI from the Parkinson's Progression Markers Initiative. We assessed gender differences for clinical and cognitive features, and dopaminergic presynaptic dysfunction in striatal or extra-striatal regions using molecular analysis of 123IFP-CIT-bindings. We applied an advanced multivariate analytical approach – partial correlations molecular connectivity analyses – to assess potential gender differences in the vulnerability of the nigrostriatal and mesolimbic dopaminergic pathways.
In the mild motor and intermediate subtypes, male patients with idiopathic PD showed poorer cognitive performances than females, who – in contrast – presented more severe anxiety symptoms. The male vulnerability emerged also in the motor system in the same subtypes with motor impairment associated with a lower dopamine binding in the putamen and more severe widespread connectivity alterations in the nigrostriatal dopaminergic pathway in males than in females. In the diffuse-malignant subtype, males showed more severe motor impairments, consistent with a lower dopamine uptake in the putamen than females. On the other hand, a severe dopaminergic depletion in several dopaminergic targets of the mesolimbic pathway, together with extensive altered connectivity in the same system, characterized females with idiopathic PD in all the subtypes. The anxiety level was associated with a lower dopaminergic binding in the amygdala only in females.
This study provides evidence on gender differences in idiopathic PD across clinical subtypes, and, remarkably, since the early phase. The clinical correlations with the nigrostriatal or mesolimbic systems in males and females support different vulnerabilities and related disease expressions. Gender differences must be considered in a precision medicine approach to preventing, diagnosing, and treating idiopathic PD.
•Dopaminergic systems show specific gender-related vulnerability in PD.•Males present a prevalent nigrostriatal derangement associated with motor symptoms severity.•Females show major changes in the mesolimbic system also related to anxiety levels.•Males and females maintain these different PD expressions regardless of the clinical subtypes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such ...treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer’s disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.
•Increased NfL in CSF and blood of proteopathic neurodegenerative diseases•Increased NfL in CSF and blood coincides with onset of proteopathic lesions in brain•NfL as disease progression and treatment response marker•Translational value and predictability of current mouse models in clinical settings
Bacioglu et al. (2016) report NfL increases in CSF and blood of murine models and human α-synucleinopathies, tauopathies, and β-amyloidosis. NfL in bodily fluid constitutes a biomarker of neurodegeneration reflecting the translational value and potential impact of current mouse models in clinical settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The final steps of the O2 cascade during exercise depend on the product of the microvascular‐to‐intramyocyte PO2${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ...(DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$). Non‐invasive methods to determine DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (mV̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$) recovery rate constant (k), measured by near‐infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW), and hypothesized that: (i) k in well oxygenated muscle (kHIGH) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH – kLOW) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half‐maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s−1 mg−1 (∼5.8 ml min−1 100 g−1). CD ranged 348 to 586 mm–2. kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min–1, P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = –0.10, P = 0.755). Δk ranged –0.26 to –2.55 min–1, and correlated with CD (r = –0.68, P = 0.015). mV̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$. Assessment of muscle k and ∆k using NIRS provides a non‐invasive window on muscle oxidative and O2 diffusing capacity.
Key points
We determined post‐exercise recovery kinetics of quadriceps muscle oxygen uptake (mV̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$) measured by near‐infrared spectroscopy (NIRS) in humans under conditions of both non‐limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables.
The mV̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (kHIGH) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity.
kHIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80).
∆k was negatively correlated with capillary density (r = −0.68) of biopsy samples.
NIRS provides non‐invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo.
figure legend A NIRS probe was positioned on vastus lateralis muscle and used to assess both muscle oxidative and oxygen diffusing capacity in vivo by intermittent arterial occlusions. Timing and duration of each occlusion were manipulated to maintain tissue saturation index within a 10 percentage range either below (LOW) or above (HIGH) half‐maximal desaturation. Recovery rate constant (k) of muscle oxygen consumption (mV̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$) obtained by NIRS was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles. Changes in recovery rate constant (k) were correlated with capillary density calculated from cross‐section of muscle samples obtained by immunofluorescence.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. Background Lamin A/C ( LMNA ) gene mutations cause a variety of phenotypes. In the cardiology ...setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases. Methods Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype. Results Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for ≥10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death. Conclusions Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
OBJECTIVETo evaluate the statistical parametric mapping (SPM) procedure for fluorodeoxyglucose (FDG)-PET imaging as a possible single-subject marker of progression to dementia in Parkinson disease ...(PD).
METHODSFifty-four consecutive patients with PD without dementia (age at onset of 59.9 ± 10.1 years, disease duration of 5.3 ± 3.4 years) entered the study. The patients underwent an extensive motor and cognitive assessment and a single-subject FDG-PET SPM evaluation at baseline. A 4-year follow-up provided disease progression and dementia diagnosis.
RESULTSThe FDG-PET SPM was evaluated by 2 expert raters allowing the identification of a “typical PD pattern” in 29 patients, whereas 25 patients presented with “atypical patterns,” namely, dementia with Lewy bodies (DLB)-like (n = 12), Alzheimer disease (AD)-like (n = 6), corticobasal syndrome (CBS)-like (n = 5), and frontotemporal dementia (FTD)-like (n = 2). At 4-year follow-up, 13 patients, all showing atypical brain metabolic patterns at baseline, progressed to dementia (PD dementia). The DLB- and AD-like SPM patterns were the best predictor for incident dementia (p < 0.005, sensitivity 85%, specificity 88%), independently from demographics or cognitive baseline classification.
CONCLUSIONSThis study suggests that FDG-PET SPM at the single-subject level might help in identifying patients with PD at risk of developing dementia.
Success in sprint kayaking depends on the propulsive power generated by trunk, pelvis, shoulder and lower limb movements. However, no studies have examined whole-body kinematics over a simulated ...distance. We aimed to study the changes in movement patterns of kayakers performing a 500-m kayak sprint. Eleven young K1 sprint kayakers (three females; age: 16.5 ± 1.9 years, height: 174.1 ± 7.1 cm and weight: 66.1 ± 6.2 kg) performed an incremental test on a kayak ergometer to assess their Peak Oxygen Uptake (V̇O
2peak
). They then performed a 500-m sprint trial on the same ergometer, and the positions of 40 reflective markers were recorded to assess whole-body kinematics. Joint angles over time were computed for the trunk and right shoulder, hip, knee, and ankle. Changes of joint kinematics during the test were assessed with Statistical Parametric Mapping, calculating at each time node the linear regression between joint angles waveforms and the time of the rowing cycle, p < .05. Cardiometabolic responses confirmed that the participants achieved a maximal effort (V̇O
2
and HR reached 99 ± 11% and 94 ± 6% of peak values, respectively). Paddle velocity negatively correlated with sprint time. The shoulder (elevation, rotation and flexion), trunk (lateral flexion and rotation) and hip (abduction) angles significantly changed over time in different phases of the stroke cycle during the simulated sprint. No significant differences over time were found for knee and ankle flexion. A high-intensity sprint may affect the shoulder, trunk and hip kinematics of kayak paddling. The kinematic analysis of kayakers' paddling during simulated metabolic-demanding tasks can provide useful insights to coaches and athletes.
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FSPLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To explore the effects of PD pathology on brain connectivity, we characterized with an emergent computational approach the brain metabolic connectome using 18FFDG-PET in early idiopathic PD patients. ...We applied whole-brain and pathology-based connectivity analyses, using sparse-inverse covariance estimation in thirty-four cognitively normal PD cases and thirty-four age-matched healthy subjects for comparisons. Further, we assessed high-order resting state networks by interregional correlation analysis. Whole-brain analysis revealed altered metabolic connectivity in PD, with local decreases in frontolateral cortex and cerebellum and increases in the basal ganglia. Widespread long-distance decreases were present within the frontolateral cortex as opposed to connectivity increases in posterior cortical regions, all suggestive of a global-scale connectivity reconfiguration. The pathology-based analyses revealed significant connectivity impairment in the nigrostriatal dopaminergic pathway and in the regions early affected by α-synuclein pathology. Notably, significant connectivity changes were present in several resting state networks especially in frontal regions. These findings expand previous imaging evidence of altered connectivity in cognitively stable PD patients by showing pathology-based connectivity changes and disease-specific metabolic architecture reconfiguration at multiple scale levels, from the earliest PD phases. These alterations go well beyond the known striato-cortical connectivity derangement supporting in vivo an extended neural vulnerability in the PD synucleinopathy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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