Identification of Parkinson's disease subtypes with distinct brain atrophy progression and its association with clinical progression.

Background: Parkinson's disease (PD) patients suffer from progressive gray matter volume (GMV) loss, but whether distinct patterns of atrophy progression exist within PD are still unclear. Objective: This study aims to identify PD subtypes with different rates of GMV loss and assess their association with clinical progression. Methods: This study included 107 PD patients (mean age: 60.06 ± 9.98 years, 70.09% male) with baseline and ≥ 3-year follow-up structural MRI scans. A linear mixed-effects model was employed to assess the rates of regional GMV loss. Hierarchical cluster analysis was conducted to explore potential subtypes based on individual rates of GMV loss. Clinical score changes were then compared across these subtypes. Results: Two PD subtypes were identified based on brain atrophy rates. Subtype 1 (n = 63) showed moderate atrophy, notably in the prefrontal and lateral temporal lobes, while Subtype 2 (n = 44) had faster atrophy across the brain, particularly in the lateral temporal region. Furthermore, subtype 2 exhibited faster deterioration in non-motor (MDS-UPDRS-Part Ⅰ, ß = 1.26 ± 0.18, P = 0.016) and motor (MDS-UPDRS-Part Ⅱ, ß = 1.34 ± 0.20, P = 0.017) symptoms, autonomic dysfunction (SCOPA-AUT, ß = 1.15 ± 0.22, P = 0.043), memory (HVLT-Retention, ß = -0.02 ± 0.01, P = 0.016) and depression (GDS, ß = 0.26 ± 0.083, P = 0.019) compared to subtype 1. Conclusion: The study has identified two PD subtypes with distinct patterns of atrophy progression and clinical progression, which may have implications for developing personalized treatment strategies.

Diagnostic value of early bedside ultrasound measurement of quadriceps femoris on in-hospital mortality of septic patients / 中华危重病急救医学

Objective:To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality.Methods:A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients.Results:A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95% CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. Conclusions:For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.

Genome-wide association study of hippocampal atrophy rate in non-demented elders.

Hippocampal atrophy rate has been correlated with cognitive decline and its genetic modifiers are still unclear. Here we firstly performed a genome-wide association study (GWAS) to identify genetic loci that regulate hippocampal atrophy rate. Six hundred and two non-Hispanic Caucasian elders without dementia were included from the Alzheimer's Disease Neuroimaging Initiative cohort. Three single nucleotide polymorphisms (SNPs) (rs4420638, rs56131196, rs157582) in the TOMM40-APOC1 region were associated with hippocampal atrophy rate at genome-wide significance and 3 additional SNPs (in TOMM40 and near MIR302F gene) reached a suggestive level of significance. Strong linkage disequilibrium between rs4420638 and rs56131196 was found. The minor allele of rs4420638 (G) and the minor allele of rs157582 (T) showed associations with lower Mini-mental State Examination score, higher Alzheimer Disease Assessment Scale-cognitive subscale 11 score and smaller entorhinal volume using both baseline and longitudinal measurements, as well as with accelerated cognitive decline. Moreover, rs56131196 (P = 1.96 × 10-454) and rs157582 (P = 9.70 × 10-434) were risk loci for Alzheimer's disease. Collectively, rs4420638, rs56131196 and rs157582 were found to be associated with hippocampal atrophy rate. Besides, they were also identified as genetic loci for cognitive decline.

Self-reported urinary impairment identifies 'fast progressors' in terms of neuronal loss in multiple system atrophy.

INTRODUCTION: MSA is an adult-onset, sporadic, progressive parkinsonian syndrome characterised by the presence of akinesia, cerebellar dysfunction, autonomic failure and pyramidal signs. Annualized-whole-brain atrophy rate (a-WBAR) is an informative way to quantify disease progression. In this longitudinal work we investigate the correlations of a-WBAR with clinical scales for motor impairment, autonomic disability and cognitive decline in MSA and explore how atrophy progresses within the brain. METHOD: Fourty-one MSA patients were studied using Structural Imaging Evaluation with Normalization of Atrophy (SIENA). SIENA is an MRI-based algorithm that quantifies brain tissue volume. Clinical parameters were explored using the 18-item Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr Scale, the Frontal Assessment Battery and the Natural History and Neuroprotection in Parkinson Plus Syndromes scale (sub-items for orthostatic and urinary functions). RESULTS: The mean (±SD) age was 60.4 years ±â€¯7.7 and a-WBAR was 1.65% ±â€¯0.9. Demographics and clinical ratings at the time of the first scan were non-significantly associated with a-WBAR. The only exception was the baseline urinary score with a weak but significant association (R2 = 0.15, p = 0.04). Progression of grey matter atrophy was detected in the left superior temporal gyrus, right middle frontal gyrus, right frontopolar region and midbrain. CONCLUSION: Urinary impairment at baseline may help to identify 'fast progressors' in terms of neuronal loss, particularly in the frontal and temporal lobes. Thus, urinary impairment should be recognized as a key target for disease modifying therapeutic interventions in MSA.

Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis.

BACKGROUND: Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. OBJECTIVE: Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. METHODS: We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. RESULTS: Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSFIgA and CSFIgM showed higher functional disability at follow-up. CONCLUSION: CSF markers of blood-brain barrier integrity and specific immune response forecast emerging gray matter pathology and disease progression in MS.

Rrelationship between liver volume atrophy rate,liver stiffness measurements and Child-Turcotte-Pugh value with Laennec histopathological classification in patients with hepatitis B cirrhosis / 重庆医学

Objective To explore the relationship between the liver volume atrophy rate,liver stiffness measurements(LSM) and Child-Turcotte-Pugh(CTP) value with the Laennec histopathological classification in the patients with hepatitis B cirrhosis and its value in the quantitative diagnosis of liver cirrhosis degree.Methods The clinicopathological data of liver biopsy tissue pathological slides,FibroScan,CT examination and hematological detection in 32 cases of hepatitis B cirrhosis were retrospectively analyzed.Liver cirrhosis was divided into mild,moderate and severe according to the Laennec liver cirrhosis histopathological classification.Then the relationship between the liver volume atrophy rate,LSM and CTP score with liver cirrhosis histopathological.Results Among 32 cases,9 cases(28.12％) were mild,12 cases(37.50％) were moderate and 11 cases(34.38％) were severe.The liver volume atrophy rates of mild,moderate and severe groups were (16.75±2.20)％,(23.11±6.67)％ and(35.55±5.70)％ respectively;LSM were(14.96±3.36),(20.21± 3.07),(37.03 ± 16.44) kPa respectively,the difference among 3 groups was statistically significant (P＜ 0.01).The CTP scores had no statistical difference among the 3 groups were(P＞0.05).The cirrhosis histopathological grade had the positive correlation with the liver volume atrophy rate and LSM(r=0.93,0.74,P＜0.01),however had no obvious correlation with the CTP scores(r=0.27,P＞0.05);the liver volume atrophy rate was positively correlated with LSM and CTP score(r=0.90,0.91,P＜0.01);while LSM had no obvious correlation with CTP score (r =0.15,P ＞ 0.05).Conclusion The more severe the cirrhosis histoathological grade,the bigger the liver volume atrophy rate and the higher the FibroScan detection value;the liver volume atrophy rate and LSM may serve as the quantitative diagnosis indicators of liver fibrosis histopathological severity.

Retrospective Diagnosis of Parkinsonian Syndromes Using Whole-Brain Atrophy Rates.

Objective: The absence of markers for ante-mortem diagnosis of idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) results in these disorders being commonly mistaken for each other, particularly in the initial stages. We aimed to investigate annualized whole-brain atrophy rates (a-WBAR) in these disorders to aid in the diagnosis between IPD vs. PSP and MSA. Methods: Ten healthy controls, 20 IPD, 39 PSP, and 41 MSA patients were studied using Structural Imaging Evaluation with Normalization of Atrophy (SIENA). SIENA is an MRI-based algorithm that quantifies brain tissue volume and does not require radiotracers. SIENA has been shown to have a low estimation error for atrophy rate over the whole brain (0.5%). Results: In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17-0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32-0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.93% ± 1.1 (CI 95% 1.5-2.2). In MSA a-WBAR was 1.65% ± 0.9 (CI 95%1.37-1.93). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in IPD (p < 0.001). a-WBAR 0.6% differentiated patients with IPD from those with PSA and MSA with 91% sensitivity and 80% specificity. Conclusions: a-WBAR within the normal range is unlikely to be observed in PSP or MSA. a-WBAR may add a potential retrospective application to improve the diagnostic accuracy of MSA and PSP vs. IPD during the first year of clinical assessment.

A comparison of measurement methods of hippocampal atrophy rate for predicting Alzheimer's dementia in the Aberdeen Birth Cohort of 1936.

INTRODUCTION: Various methods are available to measure hippocampal atrophy rate. We compared methods to predict Alzheimer's dementia. METHODS: Participants with brain imaging at ages 69 and 73 years were identified from a previous study. Simple manual measures and computationally automated volumetry were performed. Receiver operating characteristics assessed the predictive ability of each method at baseline and on logit regression analysis of two serial scans. RESULTS: Ten of 149 participants developed Alzheimer's dementia and had lower baseline volumes (3647 vs. 4194 mm3P = .002), rates of volume loss (-126 vs. -36 mm3/y; P = .001), and rates of loss in hippocampal fraction (-8.55 vs. -2.35 x 10-5/y; P = .001). Baseline volume with a rate of change gave the highest area under the curve value of 0.96. DISCUSSION: Automated volumetry measuring hippocampal size at age 69 years and subsequent rate of change predicts Alzheimer's dementia development.

CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults.

Cerebrospinal fluid (CSF) neurofilament light (NFL) is a marker of axonal degeneration. We tested whether CSF NFL levels predict hippocampal atrophy rate in cognitively healthy older adults independently of the established CSF Alzheimer's disease (AD) biomarkers, ß-amyloid 1-42, and phosphorylated tau (P-tau). We included 144 participants in a 2-year longitudinal study with baseline CSF measures and 2 magnetic resonance images. Eighty-eight participants had full data available. A subgroup of 36 participants with very low AD risk was also studied. NFL predicted hippocampal atrophy rate independently of age, ß-amyloid 1-42, and P-tau. Including NFL, P-tau, and age in the same model, higher NFL and lower P-tau predicted higher hippocampal atrophy (R2 = 0.20, NFL: ß = -0.34; p = 0.003; P-tau: ß = 0.27; p = 0.009). The results were upheld in the participants with very low AD risk. NFL predicted neurodegeneration in older adults with very low AD probability. We suggest that factors previously shown to be important for brain degeneration in mild cognitive impairment may also impact changes in normal aging, demonstrating that NFL is likely to indicate AD-independent, age-expected neurodegeneration.

Variables associated with hippocampal atrophy rate in normal aging and mild cognitive impairment.

The goal of this study was to identify factors contributing to hippocampal atrophy rate (HAR) in clinically normal older adults (NC) and participants with mild cognitive impairment (MCI). Longitudinal HAR was measured on T1-weighted magnetic resonance imaging, and the contribution of age, gender, apolipoprotein E (ApoE) ε4 status, intracranial volume, white matter lesions, and ß-amyloid (Aß) levels to HAR was determined using linear regression. Age-related effects of HAR were compared in Aß positive (Aß+) and Aß negative (Aß-) participants. Age and Aß levels had independent effects on HAR in NC, whereas gender, ApoE ε4 status, and Aß levels were associated with HAR in MCI. In multivariable models, Aß levels were associated with HAR in NC; ApoE ε4 and Aß levels were associated with HAR in MCI. In MCI, age was a stronger predictor of HAR in Aß- versus Aß+ participants. HAR was higher in Aß+ participants, but most of the HAR was because of factors other than Aß status. Age-related effects on HAR did not differ between NC versus MCI participants with the same Aß status. Therefore, we conclude that even when accounting for other covariates, Aß status, and not age, is a significant predictor of HAR; and that most of the HAR is not accounted for by Aß status in either NC or MCI.

Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22), compared with AD (n = 30) and elderly nondemented control subjects (n = 15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to control subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole brain, temporoparietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and these rates can be used as biomarkers of AD progression in patients with LB pathology.