Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aß42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aß42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

Cortical thickness reveals sex differences in verbal and visuospatial memory.

Although previous studies have reported the sex differences in behavior/cognition and the brain, the sex difference in the relationship between memory abilities and the underlying neural basis in the aging process remains unclear. In this study, we used a machine learning model to estimate the association between cortical thickness and verbal/visuospatial memory in females and males and then explored the sex difference of these associations based on a community-elderly cohort (n = 1153, age ranged from 50.42 to 86.67 years). We validated that females outperformed males in verbal memory, while males outperformed females in visuospatial memory. The key regions related to verbal memory in females include the medial temporal cortex, orbitofrontal cortex, and some regions around the insula. Further, those regions are more located in limbic, dorsal attention, and default-model networks, and are associated with face recognition and perception. The key regions related to visuospatial memory include the lateral prefrontal cortex, anterior cingulate gyrus, and some occipital regions. They overlapped more with dorsal attention, frontoparietal and visual networks, and were associated with object recognition. These findings imply the memory performance advantage of females and males might be related to the different memory processing tendencies and their associated network.

Cortical lipid metabolic pathway alteration of early Alzheimer's disease and candidate drugs screen.

BACKGROUND: Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. METHODS: The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein-protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. RESULTS: 60 lipid metabolic genes differentially expressed in early AD patients' cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. CONCLUSIONS: AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.

White Matter Plasticity Underpins Cognitive Gains After Multidomain Adaptive Computerized Cognitive Training.

BACKGROUND: This study aims to evaluate the effectiveness of computerized cognitive training (CCT) on white matter (WM) neuroplasticity and neuropsychological performance. METHODS: A total of 128 community older adults (64.36 ±â€…6.14 years) were recruited and randomly assigned to the intervention or control group. Participants in the intervention group received a home-based, multidomain, and adaptive CCT for 30 minutes, 2 days per week for 1 year. Neuropsychological assessments, diffusion magnetic resonance imaging (MRI), and T1-weighted structural MRI were performed at the pre- and post-intervention visits. RESULTS: Eighty-one of 128 participants (41 in the intervention group and 40 in the control group) completed the 1-year intervention, and 61 of them (27 in the intervention group and 34 in the control group) underwent MRI scans twice. After excluding attrition bias, a significant time-by-group interaction on the Stroop Color-Word Test (SCWT; F = 51.85, p < .001) was found, showing improvement in the intervention group and a decline in the control group. At the brain level, the intervention group exhibited increased axial diffusivity in the left posterior thalamic radiation, and this increase was significantly correlated with reduced SCWT reaction time (r = ‒0.42, p = .029). No significant time-by-group interactions were found for gray matter volume. CONCLUSIONS: Our findings suggest that conducting multidomain adaptive CCT is an effective and feasible method to counteract cognitive decline in older adults, with WM neuroplasticity underpinning cognitive improvements. This study contributes to the understanding of the neural basis for the beneficial effect of CCT for older adults.

Joint contributions from brain activity and activity-independent functional connectivity to working memory aging.

Working memory (WM) impairment has been well characterized in normal aging. Various studies have explored changes in either the regional activity or the interregional connectivity underlying the aging process of WM. We proposed that brain activity and connectivity would independently alter with aging and affect WM performance. WM was assessed with a classical N-back task during functional magnetic resonance imaging in a community-based sample comprising 168 elderly subjects (aged 55-86 years old). Following the rationale of background functional connectivity, we assessed age-related alterations in brain activity and seed-based interregional connectivity independently. Analyses revealed age-related decrease in positive activity of the inferior parietal lobule (IPL) and an increase in the negative activity of the ventral anterior cingulate cortex (ACC), and the local functional dysfunctions were accompanied by alterations in their connectivity to other cortical regions. Importantly, regional activity impairments in the IPL and ACC could mediate age-related effects on accuracy rate and reaction time, respectively, and those effects were further counterbalanced by enhancement of their background functional connectivity. We thus claimed that age-induced alterations in regional activity and interregional connectivity occurred independently and contributed to WM changes in aging. Our findings presented the way brain activity and functional connectivity interact in the late adulthood, thus providing a new perspective for understanding WM and cognitive aging.

Divergent brain regional atrophy and associated fiber disruption in amnestic and non-amnestic MCI.

BACKGROUND: Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI). METHODS: T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed. RESULTS: The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language. CONCLUSIONS: The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.

Effect of the duration of hypertension on white matter structure and its link with cognition.

The relation between hypertension (HTN) and cognition has been reported inclusive results, which may be affected by disease duration. Our study aimed to examine the influence of HTN duration on cognition and its underlying white matter (WM) changes including macrostructural WM hyperintensities (WMH) and microstructural WM integrity. A total of 1218 patients aged ≥55 years with neuropsychological assessment and a subgroup of 233 people with imaging data were recruited and divided into 3 groups (short duration: <5 years, medium duration: 5-20 years, long duration: >20 years). We found that greater HTN duration was preferentially related to worse executive function (EF), processing speed (PS), and more severe WMH, which became more significant during long duration stage. The reductions in WM integrity were evident at the early stage especially in long-range association fibers and then scattered through the whole brain. Increasing WMH and decreasing integrity of specific tracts consistently undermined EF. Furthermore, free water imaging method greatly enhanced the sensitivity in detecting HTN-related WM alterations. These findings supported that the neurological damaging effects of HTN is cumulative and neuroimaging markers of WM at macro- and microstructural level underlie the progressive effect of HTN on cognition.

Effect of transversus abdominis plane block combined with low-dose dexmedetomidine on elderly patients undergoing laparoscopic colectomy.

Introduction: Colon cancer is a common malignancy, for which surgery is currently the preferred therapy. Aim: To assess the effect of transversus abdominis plane block (TAPB) combined with low-dose dexmedetomidine on elderly patients undergoing laparoscopic colectomy. Material and methods: Sixty-two elderly patients undergoing laparoscopic colectomy between March 2021 and March 2022 were randomly selected and equally divided into Group A (low-dose dexmedetomidine) and Group B (TAPB + low-dose dexmedetomidine) by the randomized double-blind method. The treatment outcomes were compared. Results: The resting and active Visual Analogue Scale and Pittsburgh Sleep Quality Index scores were lower in Group B than those in Group A at 6 h, 1 day, 2 days and 3 days after operation (p < 0.05). The two groups had no significant differences in the levels of cluster of differentiation 4+ (CD4+), CD8+ and free Cor, CD4+/CD8+ ratio and NK cell level before anesthesia (p > 0.05). At 24 h after the operation, the level of CD4+, CD4+/CD8+ ratio and NK cell level were higher in Group B than those in Group A, and the levels of CD8+ and free Cor were lower in Group B (p < 0.05). Group B had higher partial pressure of oxygen ((45.52 ±11.14) mm Hg) and pH (7.42 ±0.06) (p < 0.05) and lower partial pressure of carbon dioxide ((4.05 ±0.32) mm Hg) than those of Group A (p < 0.05). Conclusions: TAPB combined with low-dose dexmedetomidine can exert better anesthetic, analgesic and sedative effects, and ameliorate stress responses.

Multi-domain cognition dysfunction accompanies frontoparietal and temporal amyloid accumulation in the elderly.

It is helpful to understand the pathology of Alzheimer's disease by exploring the relationship between amyloid-ß accumulation and cognition. The study explored the relationship between regional amyloid-ß accumulation and multiple cognitions and study their application value in the Alzheimer's disease diagnosis. 135 participants completed 18F-florbetapir Positron Emission Tomography (PET), structural MRI, and a cognitive battery. Partial correlation was used to examine the relationship between global and regional amyloid-ß accumulation and cognitions. Then, a support vector machine was applied to determine whether cognition-related accumulation regions can adequately distinguish the cognitively normal controls (76 participants) and mild cognitive impairment (30 participants) groups or mild cognitive impairment and Alzheimer's disease (29 participants) groups. The result showed that amyloid-ß accumulation regions were mainly located in the frontoparietal cortex, calcarine fissure, and surrounding cortex and temporal pole regions. Episodic memory-related regions included the frontoparietal cortices; executive function-related regions included the frontoparietal, temporal, and occipital cortices; and processing speed-related regions included the frontal and occipital cortices. Support vector machine analysis showed that only episodic memory-related amyloid-ß accumulation regions had better classification performance during the progression of Alzheimer's disease. Assessing regional changes in amyloid, particularly in frontoparietal regions, can aid in the early detection of amyloid-related decline in cognitive function.

Brain development mediates the relationship between self-reported poor parental monitoring and adolescent anxiety.

Adolescence is the peak period for the onset of generalized anxiety disorder (GAD). Brain networks of cognitive and affective control in adolescents are not well developed when their exposure to external stimuli suddenly increases.Reasonable parental monitoring is especially important during this period.To examine the role of parental monitoring in the development of functional brain networks of GAD, we conducted a cross-validation-based predictive study based on the functional brain networks of 192 participants. We found that a set of functional brain networks, especially the default mode network and its connectivity with the frontoparietal network, could predict the ages of adolescents, which was replicated in three independent samples.Importantly, the difference between predicted age and chronological age significantly mediated the relationship between parental monitoring and anxiety levels. These findings suggest that inadequate parental monitoring plays a crucial role in the delayed development of specific brain networks associated with GAD in adolescents. Our work highlights the important role of parental monitoring in adolescent development.

Prebiotics modulate the microbiota-gut-brain axis and ameliorate cognitive impairment in APP/PS1 mice.

PURPOSE: Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms. METHODS: Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6 weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing. RESULTS: Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aß burden and proinflammatory IL-1ß and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation. CONCLUSION: Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aß pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.

Formation of a PVP-protected C/UO2/Pt catalyst in a direct ethanol fuel cell.

In order to solve the problem that UO2 in direct ethanol fuel cell anode catalysts is easily lost in acidic solution, resulting in the degradation of catalytic performance, this paper prepared a C/UO2/PVP/Pt catalyst in three steps by adding polyvinylpyrrolidone (PVP). The test results by XRD, XPS, TEM and ICP-MS showed that PVP had a good encapsulation effect on UO2, and the actual loading rates of Pt and UO2 were similar to the theoretical values. When 10% PVP was added, the dispersion of Pt nanoparticles was significantly improved, which reduced the particle size of Pt nanoparticles and provided more ethanol electrocatalytic oxidation reaction sites. The test results by electrochemical workstation showed that the catalytic activity as well as the stability of the catalysts were optimized due to the addition of 10% PVP.

SORL1 rs1699102 Moderates the Effect of Sex on Language Network.

BACKGROUND: Language ability differs between the sexes. However, it is unclear how this sex difference is moderated by genetic factors and how the brain interacts with genetics to support this specific language capacity. Previous studies have demonstrated that the sorting protein-related receptor (SORL1) polymorphism influences cognitive function and brain structure differently in males and females and is associated with Alzheimer's disease risk. OBJECTIVE: The aim of this study was to investigate the effects of sex and the SORL1 rs1699102 (CC versus T carriers) genotype on language. METHODS: 103 non-demented Chinese older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) database were included in this study. Participants completed language tests, T1-weighted structural magnetic resonance imaging (MRI) and resting-state functional MRI. Language test performance, gray matter volume, and network connections were compared between genotype and sex groups. RESULTS: The rs1699102 polymorphism moderated the effects of sex on language performance, with the female having reversed language advantages in T carriers. The T allele carriers had lower gray matter volume in the left precentral gyrus. The effect of sex on language network connections was moderated by rs1699102; male CC homozygotes and female T carriers had higher internetwork connections, which were negatively correlated with language performance. CONCLUSION: These results suggest that SORL1 moderates the effects of sex on language, with T being a risk allele, especially in females. Our findings underscore the importance of considering the influence of genetic factors when examining sex effects.

White matter changes underlie hypertension-related cognitive decline in older adults.

Hypertension has been well recognized as a risk factor for cognitive impairment and dementia. Although the underlying mechanisms of hypertension-affected cognitive deterioration are not fully understood, white matter changes (WMCs) seem to play an important role. WMCs include low microstructural integrity and subsequent white matter macrostructural lesions, which are common on brain imaging in hypertensive patients and are critical for multiple cognitive domains. This article provides an overview of the impact of hypertension on white matter microstructural and macrostructural changes and its link to cognitive dysfunction. Hypertension may induce microstructural changes in white matter, especially for the long-range fibers such as anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFOF), and then macrostructural abnormalities affecting different lobes, especially the periventricular area. Different regions' WMCs would further exert different effects to specific cognitive domains and accelerate brain aging. As a modifiable risk factor, hypertension might provide a new perspective for alleviating and delaying cognitive impairment.

From local properties to brain-wide organization: A review of intraregional temporal features in functional magnetic resonance imaging data.

Based on the fluctuations ensembled over neighbouring neurons, blood oxygen level-dependent (BOLD) signal is a mesoscale measurement of brain signals. Intraregional temporal features (IRTFs) of BOLD signal, extracted from regional neural activities, are utilized to investigate how the brain functions in local brain areas. This literature highlights four types of IRTFs and their representative calculations including variability in the temporal domain, variability in the frequency domain, entropy, and intrinsic neural timescales, which are tightly related to cognitions. In the brain-wide spatial organization, these brain features generally organized into two spatial hierarchies, reflecting structural constraints of regional dynamics and hierarchical functional processing workflow in brain. Meanwhile, the spatial organization gives rise to the link between neuronal properties and cognitive performance. Disrupted or unbalanced spatial conditions of IRTFs emerge with suboptimal cognitive states, which improved our understanding of the aging process and/or neuropathology of brain disease. This review concludes that IRTFs are important properties of the brain functional system and IRTFs should be considered in a brain-wide manner.

Naoxin'an capsules protect brain function and structure in patients with vascular cognitive impairment.

Introduction: Vascular cognitive impairment (VCI) is one of the most common types of dementia. Naoxin'an capsule (NXA), a traditional Chinese medicine compound, has been used to treat VCI for a long time in the clinic. Previous studies proved that the NXA capsules could ameliorate the cerebral mitochondrion deficits of VCI animals. This study aimed to investigate the protectiveness of NXA on human brain structure and function in patients with VCI. Methods: In total, 100 VCI patients were enrolled in this 24-week trial and randomly divided into the NXA capsules group (n = 50) and the ginkgo biloba capsules control group (n = 50). Before and after the treatment, cognitive behavior tests and multimodal brain magnetic resonance imaging were analyzed to comprehensively evaluate the effectiveness of NXA treatment on VCI patients after 24 weeks. Results: We found that the NXA group significantly improved overall cognitive ability (Alzheimer's Disease Assessment Scale-Cognitive section, p = 0.001; Mini-Mental Status Examination, p = 0.003), memory (Rey-Osterrieth Complex Figure test, p < 0.001) and executive function (Trail Making Test-A, p = 0.024) performance after treatment compared with the control group. For brain function, the degree of centrality in the left middle frontal gyrus, right postcentral gyrus, and left supplementary motor area increased in the NXA group and decreased in the ginkgo biloba group after treatment. The fractional amplitude of low-frequency fluctuation (fALFF) of the left precentral and right superior parietal gyrus increased, and the fALFF of the right parahippocampal and left inferior temporal gyrus decreased in the NXA group after treatment. For brain structure, the gray matter density of the left postcentral gyrus increased in the NXA group after treatment, and the total volume of white matter hyperintensity showed a decreasing trend but was not statistically significant. Furthermore, the improvement effect of NXA on executive function was associated with changes in brain function. Conclusion: These findings suggest that the NXA capsules improved cognitive performance and multiregional brain function, as well as gray matter structure in the postcentral gyrus.

Altered functional coupling between the cerebellum and cerebrum in patients with amnestic mild cognitive impairment.

Cognitive processing relies on the functional coupling between the cerebrum and cerebellum. However, it remains unclear how the 2 collaborate in amnestic mild cognitive impairment (aMCI) patients. With functional magnetic resonance imaging techniques, we compared cerebrocerebellar functional connectivity during the resting state (rsFC) between the aMCI and healthy control (HC) groups. Additionally, we distinguished coupling between functionally corresponding and noncorresponding areas across the cerebrum and cerebellum. The results demonstrated decreased rsFC between both functionally corresponding and noncorresponding areas, suggesting distributed deficits of cerebrocerebellar connections in aMCI patients. Increased rsFC was also observed, which were between functionally noncorresponding areas. Moreover, the increased rsFC was positively correlated with attentional scores in the aMCI group, and this effect was absent in the HC group, supporting that there exists a compensatory mechanism in patients. The current study contributes to illustrating how the cerebellum adjusts its coupling with the cerebrum in individuals with cognitive impairment.

Hippocampus-centred grey matter covariance networks predict the development and reversion of mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) has been thought of as the transitional stage between normal ageing and Alzheimer's disease, involving substantial changes in brain grey matter structures. As most previous studies have focused on single regions (e.g. the hippocampus) and their changes during MCI development and reversion, the relationship between grey matter covariance among distributed brain regions and clinical development and reversion of MCI remains unclear. METHODS: With samples from two independent studies (155 from the Beijing Aging Brain Rejuvenation Initiative and 286 from the Alzheimer's Disease Neuroimaging Initiative), grey matter covariance of default, frontoparietal, and hippocampal networks were identified by seed-based partial least square analyses, and random forest models were applied to predict the progression from normal cognition to MCI (N-t-M) and the reversion from MCI to normal cognition (M-t-N). RESULTS: With varying degrees, the grey matter covariance in the three networks could predict N-t-M progression (AUC = 0.692-0.792) and M-t-N reversion (AUC = 0.701-0.809). Further analyses indicated that the hippocampus has emerged as an important region in reversion prediction within all three brain networks, and even though the hippocampus itself could predict the clinical reversion of M-t-N, the grey matter covariance showed higher prediction accuracy for early progression of N-t-M. CONCLUSIONS: Our findings are the first to report grey matter covariance changes in MCI development and reversion and highlight the necessity of including grey matter covariance changes along with hippocampal degeneration in the early detection of MCI and Alzheimer's disease.

Tau as a biomarker of cognitive impairment and neuropsychiatric symptom in Alzheimer's disease.

The A/T/N research framework has been proposed for the diagnosis and prognosis of Alzheimer's disease (AD). However, the spatial distribution of ATN biomarkers and their relationship with cognitive impairment and neuropsychiatric symptoms (NPS) need further clarification in patients with AD. We scanned 83 AD patients and 38 cognitively normal controls who independently completed the mini-mental state examination and Neuropsychiatric Inventory scales. Tau, Aß, and hypometabolism spatial patterns were characterized using Statistical Parametric Mapping together with [18F]flortaucipir, [18F]florbetapir, and [18F]FDG positron emission tomography. Piecewise linear regression, two-sample t-tests, and support vector machine algorithms were used to explore the relationship between tau, Aß, and hypometabolism and cognition, NPS, and AD diagnosis. The results showed that regions with tau deposition are region-specific and mainly occurred in inferior temporal lobes in AD, which extensively overlaps with the hypometabolic regions. While the deposition regions of Aß were unique and the regions affected by hypometabolism were widely distributed. Unlike Aß, tau and hypometabolism build up monotonically with increasing cognitive impairment in the late stages of AD. In addition, NPS in AD were associated with tau deposition closely, followed by hypometabolism, but not with Aß. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aß (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aß and glucose metabolism to identify cognitive impairment and NPS. Its results support tau accumulation can be used as a biomarker of clinical impairment in AD.

Manipulating Polymer Backbone Configuration via Halogenated Asymmetric End-Groups Enables Over 18% Efficiency All-Polymer Solar Cells.

High-performance all-polymer solar cells (all-PSCs) deeply rely on the joint contributions of desirable optical absorption, adaptive energy levels, and appropriate morphology. Herein, two structural analogous polymerized small-molecule acceptors (PSMAs), PYFCl-T and PYF&PYCl-T, are synthesized, and then incorporated into the PM6:PY-IT binary blends to construct ternary all-PSCs. Due to the superior compatibility of PY-IT and PYFCl-T, the ternary all-PSC based on PM6:PY-IT:PYFCl-T with 10 wt% PYFCl-T, presents higher and more balanced charge mobility, suppressed charge recombination, and faster charge-transfer kinetics, resulting in an outstanding power conversion efficiency (PCE) of 18.12% with enhanced Jsc and FF, which is much higher than that (PCE of 16.09%) of the binary all-PSCs based on PM6:PY-IT. Besides, the ternary all-PSCs also exhibit improved photostability. The conspicuous performance enhancement principally should give the credit to the miscibility-driven phase optimization of the donor and acceptor. These findings highlight the significance of polymer-backbone configuration modulation of PSMAs in morphology optimization toward boosting the device properties of all-PSCs.