Potential ocular indicators to distinguish posterior cortical atrophy and typical Alzheimer's disease: a cross-section study using optical coherence tomography angiography.

BACKGROUND: Posterior cortical atrophy (PCA) is a form of dementia that frequently displays significant visual dysfunction and relatively preserved cognitive and executive functions, thus hindering early diagnosis and treatment. This study aimed to investigate possible fundus markers in PCA patients and compare them with those of typical Alzheimer's disease (AD) patients to seek potential diagnostic patterns. METHODS: Age-matched PCA and AD patients and healthy controls (HC) completed optometry, intraocular pressure measurement, neuropsychologic assessments, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) examination in one visit. Overall, six outcomes of thicknesses of various retinal layers and seven outcomes of the retinal microvascular network were calculated. After adjusting for age, sex, and years of education, the OCT and OCTA results were analyzed using analysis of covariance and generalized linear models. Correlation analyses were performed using Spearman correlation, and ROC curves were plotted. RESULTS: Twelve PCA patients, nineteen AD patients, and thirty HC, aged 45-80 years were included. Fifty HC, thirty AD, and twenty PCA eyes were available for foveal avascular zone (FAZ) area analysis; forty-nine HC, thirty-four AD, and eighteen PCA eyes were available for OCT and OCTA assessments. PCA patients had thinner retinal nerve fiber layer and ganglion cell layer + inner plexiform layer than HC in the 0-3 mm circle and 1-3 mm ring. Few structural differences were observed between the AD group and the other two groups. The flow area of the superficial capillary plexus and the intermediate capillary plexus was smaller in the PCA group than in the HC group in the 0-1 mm circle, 0-3 mm circle. MMSE performed better than any combination of optical parameters in identifying AD and PCA from HC (AUC = 1), while the combination of MoCA, retinal thickness and vascular density of ICP in the 1-3 mm ring, with flow area of ICP in the 0-1 mm circle showed the strongest ability to distinguish PCA from AD (AUC = 0.944). CONCLUSIONS: PCA patients exhibited similar impairment patterns to AD patients in the fundus structure and microvascular network. OCTA may aid in the non-invasive detection of AD and PCA, but still remains to be substantiated.

Autoimmunity and Frontotemporal Lobar Degeneration: From Laboratory Study to Clinical Practice.

Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases with heterogenous clinical, genetic, and pathological characteristics that show similar impairment of areas in the frontal and/or temporal lobes. Prime doctors' lack of awareness of this complex disease makes early identification and accurate intervention difficult. Autoimmune diseases and autoantibodies are manifestations of different levels of autoimmune reactions. This review presents research findings examining the relationship between autoimmunity and FTLD in terms of autoimmune diseases and autoantibodies with a focus on identifying potential diagnosis and treatment approaches. The findings indicate that the same or similar pathophysiological mechanisms may exist from clinical, genetic, and pathological perspectives. However, the existing evidence is not sufficient to extract substantial conclusions. On the basis of the current situation, we propose future research patterns using prospective studies on large populations and combined clinical and experimental research. Autoimmune reactions or, more generally, inflammatory reactions should receive increased attention from doctors and scientists of all disciplines.

Characterizing Differences in Functional Connectivity Between Posterior Cortical Atrophy and Semantic Dementia by Seed-Based Approach.

Background: Posterior cortical atrophy (PCA) and semantic dementia (SD) are focal syndromes involving different cerebral regions. This study aimed to demonstrate the existence of abnormal functional connectivity (FC) with an affected network in PCA and SD. Methods: A total of 10 patients with PCA, 12 patients with SD, and 11 controls were recruited to undergo a detailed clinical history interview and physical examination, neuropsychological assessments, and PET/MRI scan. Seed-based FC analyses were conducted to construct FC in language network, visual network, and salience network. The two-sample t-test was performed to reveal distinct FC patterns in PCA and SD, and we further related the FC difference to cognition. Meanwhile, the uptake value of fluorodeoxyglucose in regions with FC alteration was also extracted for comparison. Results: We found a global cognitive impairment in patients with PCA and SD. The results of FC analyses showed that patients with PCA present decreased FC in left precentral gyrus to left V1 and increased FC in right inferior frontal gyrus to right V1 in the visual network, right medial frontal gyrus and left fusiform to left anterior temporal lobe and post-superior temporal gyrus in the language network, and left superior temporal gyrus to left anterior insula in the salience network, which were related to cognitive function. Patients with SD had decreased FC from right superior frontal gyrus, right middle frontal gyrus and right superior frontal gyrus to left anterior temporal lobe, or post-superior temporal gyrus in the language network, as well as left superior frontal gyrus to right anterior insula in the salience network, positively relating to cognitive function, but increased FC in the right superior temporal gyrus to left anterior temporal lobe in the language network, and right insula and left anterior cingulum to right anterior insula in the salience network, negatively relating to cognitive function. Most of the regions with FC change in patients with PCA and SD had abnormal metabolism simultaneously. Conclusion: Abnormal connectivity spread over the cortex involving language and salience networks was common in patients with PCA and SD, whereas FC change involving the visual network was unique to patients with PCA. The FC changes were matched for cognitive deficits.

Serum Metabolites Differentiate Amnestic Mild Cognitive Impairment From Healthy Controls and Predict Early Alzheimer's Disease via Untargeted Lipidomics Analysis.

Background and Aim: Alzheimer's disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD. Methods: We recruited 107 participants including 23 healthy controls (HC), 21 amnestic mild cognitive impairment (aMCI), 24 non-amnestic mild cognitive impairment (naMCI) and 39 AD patients. Via liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis, we compared differences in serum lipid metabolites among these patient groups and further elucidated biomarkers that differentiate aMCI from HC. Results: There were significant differences of serum lipid metabolites among the groups, and 20 metabolites were obtained under negative ion mode from HC and aMCI comparison. Notably, 16:3 cholesteryl ester, ganglioside GM3 (d18:1/9z-18:1) and neuromedin B were associated with cognition and increased the predictive effect of aMCI to 0.98 as revealed by random forest classifier. The prediction model composed of MoCA score, 16:3 cholesteryl ester and ganglioside GM3 (d18:1/9z-18:1) had good predictive performance for aMCI. Glycerophospholipid metabolism was a pathway common among HC/aMCI and aMCI/AD groups. Conclusion: This study provides preliminary evidence highlighting that 16:3 cholesteryl ester were useful for AD disease monitoring while ganglioside GM3 (d18:1/9z-18:1) and neuromedin B discriminated aMCI from HC, which can probably be applied in clinic for early predicting of AD.

TDP-43 and Limbic-Predominant Age-Related TDP-43 Encephalopathy.

Through a number of an extensive autopsy, biomarker, and genomics studies, researchers have recently defined a novel type of dementia known as limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE is perhaps best characterized by the presence of hyperphosphorylated TDP-43, which plays multi-functional roles through interactions with DNA and RNA, leading to significant alterations in the transcription and translation of particular genes. As individuals of advanced age represent a rapidly growing demographic group globally, there is a steadily increasing rate of LATE incidence that has to date received insufficient recognition despite its serious implications for public health. TDP-43 is the common pathology of various age-related dementia, therefore, it may be a potential and promising therapeutic target for such diseases. In the present review, we discuss the pathways regulating TDP-43 expression, metabolism, and disease activity in order to better understand the link between TDP-43 proteinopathy and LATE at the genetic, pathological, and clinical levels.