A novel birnavirus identified as the causative agent of summer atrophy of pearl oyster (Pinctada fucata (Gould)).

The Akoya pearl oyster (Pinctada fucata (Gould)) is the most important species for pearl cultivation in Japan. Mass mortality of 0-year-old juvenile oysters and anomalies in adults, known as summer atrophy, have been observed in major pearl farming areas during the season when seawater temperatures exceed about 20 °C since 2019. In this study, we identified a novel birnavirus as the pathogen of summer atrophy and named it Pinctada birnavirus (PiBV). PiBV was first presumed to be the causative agent when it was detected specifically and frequently in the infected oysters in a comparative metatranscriptomics of experimentally infected and healthy pearl oysters. Subsequently, the symptoms of summer atrophy were reproduced by infection tests using purified PiBV. Infection of juvenile oysters with PiBV resulted in an increase in the PiBV genome followed by the atrophy of soft body and subsequent mortality. Immunostaining with a mouse antiserum against a recombinant PiBV protein showed that the virus antigen was localized mainly in the epithelial cells on the outer surface of the mantle. Although the phylogenetic analysis using maximum likelihood method placed PiBV at the root of the genus Entomobirnavirus, the identity of the bi-segmented, genomic RNA to that of known birnaviruses at the full-length amino acid level was low, suggesting that PiBV forms a new genus. The discovery of PiBV will be the basis for research to control this emerging disease.

Exploration of neuroanatomical characteristics to differentiate prodromal Alzheimer's disease from cognitively unimpaired amyloid-positive individuals.

Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the whole-brain level that differentiate prodromal Alzheimer's disease (AD) from cognitively unimpaired amyloid-positive individuals (CU A+) in relation to amyloid deposition and regional atrophy. We included 45 CU A+ participants and 135 participants with amyloid-positive prodromal AD matched 1:3 by age, sex, and education. All participants underwent 18F-florbetaben positron emission tomography and 3D structural T1-weighted magnetic resonance imaging. We compared the standardized uptake value ratios (SUVRs) and volumes in 80 regions of interest (ROIs) between CU A+ and prodromal AD groups using independent t-tests, and employed the least absolute selection and shrinkage operator (LASSO) logistic regression model to identify ROIs associated with prodromal AD in relation to amyloid deposition, regional atrophy, and their interaction. After applying False Discovery Rate correction at < 0.1, there were no differences in global and regional SUVR between CU A+ and prodromal AD groups. Regional volume differences between the two groups were observed in the amygdala, hippocampus, entorhinal cortex, insula, parahippocampal gyrus, and inferior temporal and parietal cortices. LASSO logistic regression model showed significant associations between prodromal AD and atrophy in the entorhinal cortex, inferior parietal cortex, both amygdalae, and left hippocampus. The mean SUVR in the right superior parietal cortex (beta coefficient = 0.0172) and its interaction with the regional volume (0.0672) were also selected in the LASSO model. The mean SUVR in the right superior parietal cortex was associated with an increased likelihood of prodromal AD (Odds ratio [OR] 1.602, p = 0.014), particularly in participants with lower regional volume (OR 3.389, p < 0.001). Only regional volume differences, not amyloid deposition, were observed between CU A+ and prodromal AD. The reduced volume in the superior parietal cortex may play a significant role in the progression to prodromal AD through its interaction with amyloid deposition in that region.

[Features of the clinical and neuroimaging picture in patients with early-onset Alzheimer's disease]. / Osobennosti klinicheskoi i neirovizualizatsionnoi kartiny u patsientov s bolezn'yu Al'tsgeimera s rannim nachalom.

The most common cause of severe cognitive impairment in adults is Alzheimer's disease (AD). Depending on the age of onset, AD is divided into early (<65 years) and late (≥65 years) forms. Early-onset AD (EOAD) is significantly less common than later-onset AD (LOAD) and accounts for only about 5-10% of cases. However, its medical and social significance, as a disease leading to loss of ability to work and legal capacity, as well as premature death in patients aged 40-64 years, is extremely high. Patients with EOAD compared with LOAD have a greater number of atypical clinical variants - 25% and 6-12.5%, respectively, which complicates the differential diagnosis of EOAD with other neurodegenerative diseases. However, the typical classical amnestic variant predominates in both EOAD and LOAD. Also, patients with EOAD have peculiarities according to neuroimaging data: when performing MRI of the brain, patients with EOAD often have more pronounced parietal atrophy and less pronounced hippocampal atrophy compared to patients with LOAD. The article pays attention to the features of the clinical and neuroimaging data in patients with EOAD; a case of a patient with EOAD is presented.

The Association between Dietary Protein Intake and Sources and the Rate of Longitudinal Changes in Brain Structure.

Few studies have examined dietary protein intake and sources, in combination with longitudinal changes in brain structure markers. Our study aimed to examine the association between dietary protein intake and different sources of dietary protein, with the longitudinal rate of change in brain structural markers. A total of 2723 and 2679 participants from the UK Biobank were separately included in the analysis. The relative and absolute amounts of dietary protein intake were calculated using a 24 h dietary recall questionnaire. The longitudinal change rates of brain structural biomarkers were computed using two waves of brain imaging data. The average interval between the assessments was three years. We utilized multiple linear regression to examine the association between dietary protein and different sources and the longitudinal changes in brain structural biomarkers. Restrictive cubic splines were used to explore nonlinear relationships, and stratified and sensitivity analyses were conducted. Increasing the proportion of animal protein in dietary protein intake was associated with a slower reduction in the total hippocampus volume (THV, ß: 0.02524, p < 0.05), left hippocampus volume (LHV, ß: 0.02435, p < 0.01) and right hippocampus volume (RHV, ß: 0.02544, p < 0.05). A higher intake of animal protein relative to plant protein was linked to a lower atrophy rate in the THV (ß: 0.01249, p < 0.05) and LHV (ß: 0.01173, p < 0.05) and RHV (ß: 0.01193, p < 0.05). Individuals with a higher intake of seafood exhibited a higher longitudinal rate of change in the HV compared to those that did not consume seafood (THV, ß: 0.004514; p < 0.05; RHV, ß: 0.005527, p < 0.05). In the subgroup and sensitivity analyses, there were no significant alterations. A moderate increase in an individual's intake and the proportion of animal protein in their diet, especially from seafood, is associated with a lower atrophy rate in the hippocampus volume.

Protective role of pretreatment with Anisodamine against sepsis-induced diaphragm atrophy via inhibiting JAK2/STAT3 pathway.

There is an increasing tendency for sepsis patients to suffer from diaphragm atrophy as well as mortality. Therefore, reducing diaphragm atrophy could benefit sepsis patients' prognoses. Studies have shown that Anisodamine (Anis) can exert antioxidant effects when blows occur. However, the role of Anisodamine in diaphragm atrophy in sepsis patients has not been reported. Therefore, this study investigated the antioxidant effect of Anisodamine in sepsis-induced diaphragm atrophy and its mechanism. We used cecal ligation aspiration (CLP) to establish a mouse septic mode and stimulated the C2C12 myotube model with lipopolysaccharide (LPS). After treatment with Anisodamine, we measured the mice's bodyweight, diaphragm weight, fiber cross-sectional area and the diameter of C2C12 myotubes. The malondialdehyde (MDA) levels in the diaphragm were detected using the oxidative stress kit. The expression of MuRF1, Atrogin1 and JAK2/STAT3 signaling pathway components in the diaphragm and C2C12 myotubes was measured by RT-qPCR and Western blot. The mean fluorescence intensity of ROS in C2C12 myotubes was measured by flow cytometry. Meanwhile, we also measured the levels of Drp1 and Cytochrome C (Cyt-C) in vivo and in vitro by Western blot. Our study revealed that Anisodamine alleviated the reduction in diaphragmatic mass and the loss of diaphragmatic fiber cross-sectional area and attenuated the atrophy of the C2C12 myotubes by inhibiting the expression of E3 ubiquitin ligases. In addition, we observed that Anisodamine inhibited the JAK2/STAT3 signaling pathway and protects mitochondrial function. In conclusion, Anisodamine alleviates sepsis-induced diaphragm atrophy, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway.

Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles.

Glial fibrillary acidic protein (GFAP), a proxy of astrocyte reactivity, has been proposed as biomarker of Alzheimer's disease. However, there is limited information about the correlation between blood biomarkers and post-mortem neuropathology. In a single-centre prospective clinicopathological cohort of 139 dementia patients, for which the time-frame between GFAP level determination and neuropathological assessment was exceptionally short (on average 139 days), we analysed this biomarker, measured at three time points, in relation to proxies of disease progression such as cognitive decline and brain weight. Most importantly, we investigated the use of blood GFAP to detect the neuropathological hallmarks of Alzheimer's disease, while accounting for potential influences of the most frequent brain co-pathologies. The main findings demonstrated an association between serum GFAP level and post-mortem tau pathology (ß = 12.85; P < 0.001) that was independent of amyloid deposits (ß = 13.23; P = 0.02). A mediation analysis provided additional support for the role of astrocytic activation as a link between amyloid and tau pathology in Alzheimer's disease. Furthermore, a negative correlation was observed between pre-mortem serum GFAP and brain weight at post-mortem (r = -0.35; P < 0.001). This finding, together with evidence of a negative correlation with cognitive assessments (r = -0.27; P = 0.005), supports the role of GFAP as a biomarker for disease monitoring, even in the late phases of Alzheimer's disease. Moreover, the diagnostic performance of GFAP in advanced dementia patients was explored, and its discriminative power (area under the receiver operator characteristic curve at baseline = 0.91) in differentiating neuropathologically-confirmed Alzheimer's disease dementias from non-Alzheimer's disease dementias was determined, despite the challenging scenario of advanced age and frequent co-pathologies in these patients. Independently of Alzheimer's disease, serum GFAP levels were shown to be associated with two other pathologies targeting the temporal lobes-hippocampal sclerosis (ß = 3.64; P = 0.03) and argyrophilic grain disease (ß = -6.11; P = 0.02). Finally, serum GFAP levels were revealed to be correlated with astrocyte reactivity, using the brain GFAP-immunostained area as a proxy (ρ = 0.21; P = 0.02). Our results contribute to increasing evidence suggesting a role for blood GFAP as an Alzheimer's disease biomarker, and the findings offer mechanistic insights into the relationship between blood GFAP and Alzheimer's disease neuropathology, highlighting its ties with tau burden. Moreover, the data highlighting an independent association between serum GFAP levels and other neuropathological lesions provide information for clinicians to consider when interpreting test results. The longitudinal design and correlation with post-mortem data reinforce the robustness of our findings. However, studies correlating blood biomarkers and neuropathological assessments are still scant, and further research is needed to replicate and validate these results in diverse populations.

Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy.

INTRODUCTION: We aimed to assess the effect of antidepressant use on dementia risk, cognitive decline, and brain atrophy. METHODS: In this prospective cohort study, we included 5511 dementia-free participants (Mini-Mental State Examination [MMSE] > 25) of the Rotterdam study (57.5% women, mean age 70.6 years). Antidepressant use was extracted from pharmacy records from 1991 until baseline (2002-2008). Incident dementia was monitored from baseline until 2018, with repeated cognitive assessment and magnetic resonance imaging (MRI) every 4 years. RESULTS: Compared to never use, any antidepressant use was not associated with dementia risk (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.92-1.41), or with accelerated cognitive decline or atrophy of white and gray matter. Compared to never use, dementia risk was somewhat higher with tricyclic antidepressants (HR 1.36, 95% CI 1.01-1.83) than with selective serotonin reuptake inhibitors (HR 1.12, 95% CI 0.81-1.54), but without dose-response relationships, accelerated cognitive decline, or atrophy in either group. DISCUSSION: Antidepressant medication in adults without indication of cognitive impairment was not consistently associated with long-term adverse cognitive effects. HIGHLIGHTS: Antidepressant medications are frequently prescribed, especially among older adults. In this study, antidepressant use was not associated with long-term dementia risk. Antidepressant use was not associated with cognitive decline or brain atrophy. Our results support safe prescription in an older, cognitively healthy population.

Cross-sectional associations between multisensory impairment and brain volumes in older adults: Baltimore Longitudinal Study of Aging.

Sensory impairment and brain atrophy is common among older adults, increasing the risk of dementia. Yet, the degree to which multiple co-occurring sensory impairments (MSI across vision, proprioception, vestibular function, olfactory, and hearing) are associated with brain morphometry remain unexplored. Data were from 208 cognitively unimpaired participants (mean age 72 ± 10 years; 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Multiple linear regression models were used to estimate cross-sectional associations between MSI and regional brain imaging volumes. For each additional sensory impairment, there were associated lower orbitofrontal gyrus and entorhinal cortex volumes but higher caudate and putamen volumes. Participants with MSI had lower mean volumes in the superior frontal gyrus, orbitofrontal gyrus, superior parietal lobe, and precuneus compared to participants with < 2 impairments. While MSI was largely associated with lower brain volumes, our results suggest the possibility that MSI was associated with higher basal ganglia volumes. Longitudinal analyses are needed to evaluate the temporality and directionality of these associations.

The impact of physical exercise on hippocampal atrophy in mild cognitive impairment and Alzheimer's disease: a meta-analysis.

Physical activity (PA) is a promising therapeutic for Alzheimer's disease (AD). Only a handful of meta-analyses have studied the impact of PA interventions on regional brain volumes, and none to date has solely included studies on effect of PA on regional brain volumes in individuals with cognitive impairment (CI). In this meta-analysis, we examined whether there is support for the hypothesis that PA interventions positively impact hippocampal volume (HV) in individuals with CI. We also assessed whether the level of CI [mild CI (MCI) vs. AD] impacted this relationship. We identified six controlled trials that met inclusion criteria. These included 236 participants with AD, MCI, or preclinical AD. Data were extracted and analyzed following Cochrane guidelines. We used a random-effects model to estimate the mean change in HV pre- and post-exercise intervention. Forest plots, Hedges' g funnel plots, and Egger's test were used to assess unbiasedness and visualize intervention effects, and Tau 2 , Cochran's Q, and I 2 were calculated to assess heterogeneity. The primary analysis revealed a significant positive effect of PA on total HV. However, sub-group analyses indicated a significant preservation of HV only in individuals with MCI, but not in those with AD. Egger's test indicated no evidence of publication bias. Subgroup analyses also revealed significant heterogeneity only within the MCI cohort for the total and left HV. PA demonstrated a moderate, significant effect in preserving HV among individuals with MCI, but not AD, highlighting a therapeutic benefit, particularly in earlier disease stages.

Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology.

INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aß) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aß, as assessed by 18F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape. RESULTS: Frontal WMH, occipital WMH, and Aß were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aß. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aß-vulnerable subregions. DISCUSSION: Hippocampal degeneration is differentially sensitive to SVD and Aß pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia.

Longitudinal optical coherence tomography indices in idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) may result in optic nerve fiber loss and even atrophy. The timing of the optical coherence tomography (OCT) indices reaching the lowest point (nadir) and the factors that predict the patient's anatomical outcome are not known. We aimed to determine the timing and the factors that affect nadir retinal nerve fiber layer (RNFL) thickness. The medical records of 99 IIH patients who were treated from December 2009 to January 2020 were retrospectively reviewed. The mean RNFL thickness at presentation was 263.5 ± 106.4 µm. The mean time to nadir was 7.9 ± 6.3 months. The average RNFL and ganglion cell complex (GCC) thickness at the nadir were 92.6 ± 14.5 µm (47% showed thinning) and 77.9 ± 27.8 µm (70% showed thinning), respectively. The Frisén disc edema stage and average RNFL thickness at baseline correlated with a longer time to nadir, (r = 0.28 P = 0.003 and r = 0.24, P = 0.012, respectively). The nadir average RNFL thickness and the nadir average GCC thickness (r = 0.32, P = 0.001, r = 0.29, P = 0.002, respectively) correlated with the baseline visual field mean deviation. The final anatomical outcome of IIH episodes in this study resulted in RNFL and GCC thinning. The time to RNFL nadir and its values correlated with IIH severity at presentation.

Growth impairment in children with atrophic autoimmune thyroiditis and pituitary hyperplasia.

BACKGROUND: Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. METHODS: Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations. RESULTS: At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex. CONCLUSIONS: This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.

Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis.

While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS. Leveraging our dataset with over 800 participants enrolled for more than 12 years, we find that IPL atrophy directly precedes progression and propose that synaptic loss is predictive of functional decline. Using a blood proteome-wide analysis, we demonstrate a strong correlation between demyelination, glial activation, and synapse loss independent of neuroaxonal injury. In summary, monitoring synaptic injury is a biologically relevant approach that reflects a potential driver of progression.

Characteristics of beta parapapillary atrophy in primary angle-closure suspect.

OBJECTIVE: To investigate the characteristics of beta parapapillary atrophy (ß-PPA) in patients with primary angle-closure suspect (PACS). METHODS AND ANALYSIS: In total, 215 and 259 eyes with PACS and non-PACS (NPACS), respectively, were enrolled in this observational, cross-sectional study. Stereoscopic fundus and optical coherence tomography images were used to characterise ß-PPA; the former was also used to measure the major ß-PPA parameters. Univariate and multiple logistic regression analyses were used to identify the factors correlated with the presence of ß-PPA and with ß-PPA parameters. RESULTS: The ß-PPA occurrence rates were 48.80% and 44.40% in the PACS and NPACS groups, respectively, with no significant difference between groups. Compared with that in the NPACS group, the ß-PPA area was significantly larger (p=0.005) in the PACS group, but the angular extent and maximum radial length did not differ between groups (p=0.110 and 0.657, respectively) after adjusting for age and axial length. The presence of ß-PPA was associated with older age (OR 1.057, 95% CI 1.028 to 1.088, p<0.001) and larger disc area (OR 1.716, 95% CI 1.170 to 2.517, p=0.006). A larger ß-PPA area was associated with older age (p=0.014), greater vertical cup-to-disc ratio (p=0.028), larger disc area (p<0.001) and PACS diagnosis (p=0.035). CONCLUSION: 48.80% of participants with PACS had ß-PPA, which is slightly larger than NPACS. The area of ß-PPA was larger in PACS, while the angular extent and maximum radial length did not differ between groups.

Predictors of multiple sclerosis progression: A systematic review of conventional magnetic resonance imaging studies.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic neurodegenerative disorder that affects the central nervous system (CNS) and results in progressive clinical disability and cognitive decline. Currently, there are no specific imaging parameters available for the prediction of longitudinal disability in MS patients. Magnetic resonance imaging (MRI) has linked imaging anomalies to clinical and cognitive deficits in MS. In this study, we aimed to evaluate the effectiveness of MRI in predicting disability, clinical progression, and cognitive decline in MS. METHODS: In this study, according to PRISMA guidelines, we comprehensively searched the Web of Science, PubMed, and Embase databases to identify pertinent articles that employed conventional MRI in the context of Relapsing-Remitting and progressive forms of MS. Following a rigorous screening process, studies that met the predefined inclusion criteria were selected for data extraction and evaluated for potential sources of bias. RESULTS: A total of 3028 records were retrieved from database searching. After a rigorous screening, 53 records met the criteria and were included in this study. Lesions and alterations in CNS structures like white matter, gray matter, corpus callosum, thalamus, and spinal cord, may be used to anticipate disability progression. Several prognostic factors associated with the progression of MS, including presence of cortical lesions, changes in gray matter volume, whole brain atrophy, the corpus callosum index, alterations in thalamic volume, and lesions or alterations in cross-sectional area of the spinal cord. For cognitive impairment in MS patients, reliable predictors include cortical gray matter volume, brain atrophy, lesion characteristics (T2-lesion load, temporal, frontal, and cerebellar lesions), white matter lesion volume, thalamic volume, and corpus callosum density. CONCLUSION: This study indicates that MRI can be used to predict the cognitive decline, disability progression, and disease progression in MS patients over time.

Peripapillary atrophy area predicts the decrease of macular choroidal thickness in young adults during myopia progression.

OBJECTIVE: This study aimed to investigate the influence of peripapillary atrophy (PPA) area and axial elongation on the longitudinal changes in macular choroidal thickness (ChT) in young individuals with myopia. METHODS AND ANALYSIS: In this longitudinal investigation, 431 eyes-342 categorised as non-high myopia (non-HM) and 89 as HM-were examined for 2 years. Participants were examined with swept-source optical coherence tomography. The macular ChT, PPA area and axial length (AL) were measured at baseline and follow-up visits. Multiple regression analysis was performed to identify factors associated with ChT changes. The areas under the receiver operating characteristic curves were analysed to ascertain the predictive capacity of the PPA area and axial elongation for the reduction in macular ChT. RESULTS: Initial measurements revealed that the average macular ChT was 240.35±56.15 µm in the non-HM group and 198.43±50.27 µm in the HM group (p<0.001). It was observed that the HM group experienced a significantly greater reduction in average macular ChT (-7.35±11.70 µm) than the non-HM group (-1.85±16.95 µm, p=0.004). Multivariate regression analysis showed that a greater reduction of ChT was associated with baseline PPA area (ß=-26.646, p<0.001) and the change in AL (ß=-35.230, p<0.001). The combination of the baseline PPA area with the change in AL was found to be effective in predicting the decrease in macular ChT, with an area under the curve of 0.741 (95% CI 0.694 to 0.787). CONCLUSION: Over 2 years, eyes with HM exhibit a more significant decrease in ChT than those without HM. Combining the baseline PPA area with the change in AL could be used to predict the decrease of macular ChT.

Quantitative Assessment of Fundus Tessellated Density in Highly Myopic Glaucoma Using Deep Learning.

Purpose: To characterize the fundus tessellated density (FTD) in highly myopic glaucoma (HMG) and high myopia (HM) for discovering early signs and diagnostic markers. Methods: This retrospective cross-sectional study included hospital in-patients with HM (133 eyes) and HMG (73 eyes) with an axial length ≥26 mm at Zhongshan Ophthalmic Center. Using deep learning, FTD was quantified as the average exposed choroid area per unit area on fundus photographs in the global, macular, and disc regions. FTD-associated factors were assessed using partial correlation. Diagnostic efficacy was analyzed using the area under the curve (AUC). Results: HMG patients had lower global (0.20 ± 0.12 versus 0.36 ± 0.09) and macular FTD (0.25 ± 0.14 vs. 0.40 ± 0.09) but larger disc FTD (0.24 ± 0.11 vs. 0.19 ± 0.07) than HM patients in the tessellated fundus (all P < 0.001). In the macular region, nasal FTD was lowest in the HM (0.26 ± 0.13) but highest in the HMG (0.32 ± 0.13) compared with the superior, inferior, and temporal subregions (all P < 0.05). A fundus with a macular region nasal/temporal (NT) FTD ratio > 0.96 (AUC = 0.909) was 15.7 times more indicative of HMG than HM. A higher macular region NT ratio with a lower horizontal parapapillary atrophy/disc ratio indicated a higher possibility of HMG than HM (AUC = 0.932). Conclusions: FTD differs in degree and distribution between HMG and HM. A higher macular NT alone or with a lower horizontal parapapillary atrophy/disc ratio may help differentiate HMG. Translational Relevance: Deep learning-based FTD measurement could potentially assist glaucoma diagnosis in HM.

Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals.

BACKGROUND: Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods. METHODS: This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models. RESULTS: A total of 367 participants (48 A + T + , 86 A + T - , 63 A - T + , and 170 A - T - ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T - and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A - T - group (lateral ventricle: ß = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T - , and ß = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: ß = - 0.19 /year [- 0.36 to - 0.02], P = .029 for A + T - , and ß = - 0.59 /year [- 0.80 to - 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (ß = - 2.782 cm3/year [- 4.060 to - 1.504], P < .001), hippocampus (ß = - 0.057 cm3/year [- 0.085 to - 0.029], P < .001), and AD-signature regions (ß = - 0.02 mm/year [- 0.03 to - 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A - T - group (adjusted hazard ratio = 3.35 [1.76 to 6.39]). CONCLUSIONS: In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression.

Localizing apraxia in corticobasal syndrome: a morphometric MRI study.

Apraxia localization has relied on voxel-based, lesion-symptom mapping studies in left hemisphere stroke patients. Studies on the neural substrates of different manifestations of apraxia in neurodegenerative disorders are scarce. The primary aim of this study was to look into the neural substrates of different manifestations of apraxia in a cohort of corticobasal syndrome patients (CBS) by use of cortical thickness. Twenty-six CBS patients were included in this cross-sectional study. The Goldenberg apraxia test (GAT) was applied. 3D-T1-weighted images were analyzed via the automated recon-all Freesurfer version 6.0 pipeline. Vertex-based multivariate General Linear Model analysis was applied to correlate GAT scores with cortical thickness. Deficits in imitation of meaningless gestures correlated with bilateral superior parietal atrophy, extending to the angular and supramarginal gyri, particularly on the left. Finger imitation relied predominantly on superior parietal lobes, whereas the left angular and supramarginal gyri, in addition to superior parietal lobes, were critical for hand imitation. The widespread bilateral clusters of atrophy in CBS related to apraxia indicate different pathophysiological mechanisms mediating praxis in neurodegenerative disorders compared to vascular lesions, with implications both for our understanding of praxis and for the rehabilitation approaches of patients with apraxia.