Differential correlations of changes in in vivo neuroimaging markers of hippocampal volume and arteriolosclerosis with declining financial and health literacy in old age.

Financial and health literacy is essential for older adults to navigate complex decision processes in late life. However, the neurobiological basis of age-related decline in financial and health literacy is poorly understood. This study aimed to characterize progression of neurodegenerative and vascular conditions over time, and to assess how these changes coincide with declining financial and health literacy in old age. Data came from 319 community-living older adults who were free of dementia at baseline, and underwent annual literacy assessments, as well as biennial 3-Tesla neuroimaging scans. Financial and health literacy was assessed using a battery of 32 items. Two in vivo neuroimaging markers of neurodegenerative and cerebrovascular conditions were used, i.e., hippocampal volume and the ARTS marker of arteriolosclerosis. A multivariate linear mixed effects model estimated the simultaneous changes in financial and health literacy, hippocampal volume, and the ARTS score. Over a mean of 7 years of follow-up, these older adults experienced a significant decline in financial and health literacy, a significant reduction in hippocampal volume, and a significant progression in ARTS score. Individuals with faster hippocampal atrophy had faster decline in literacy. Similarly, those with faster progression in ARTS also had faster decline in literacy. The correlation between the rates of hippocampal atrophy and declining literacy, however, was stronger than the correlation between the progression of ARTS with declining literacy. These findings suggest that neurodegeneration and, to a lesser extent, cerebrovascular conditions are correlated with declining financial and health literacy in old age.

Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients.

INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-ß1-42 (Aß42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. HIGHLIGHTS: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aß42 status in 11 memory clinic cohorts. Aß42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.

Cognitive profile in cerebral small vessel disease: comparison between cerebral amyloid angiopathy and hypertension-related microangiopathy.

Cerebral amyloid angiopathy (CAA) is recognized as a cause of cognitive impairment, but its cognitive profile needs to be characterized, also respect to hypertension-related microangiopathy (HA). We aimed at comparing difference or similarity of CAA and HA patients' cognitive profiles, and their associated factors. Participants underwent an extensive clinical, neuropsychological, and neuroimaging protocol. HA patients (n = 39) were more frequently males, with history of vascular risk factors than CAA (n = 32). Compared to HA, CAA patients presented worse performance at MoCA (p = 0.001) and semantic fluency (p = 0.043), and a higher prevalence of amnestic MCI (46% vs. 68%). In univariate analyses, multi-domain MCI was associated with worse performance at MoCA, Rey Auditory Verbal Learning Test (RAVLT), and semantic fluency in CAA patients, and with worse performance at Symbol Digit Modalities Test (SDMT) and phonemic fluency in HA ones. In multivariate models, multi-domain deficit remained as the only factor associated with RAVLT (ß = - 0.574) in CAA, while with SDMT (ß = - 0.364) and phonemic fluency (ß = - 0.351) in HA. Our results highlight different patterns of cognitive deficits in CAA or HA patients. While HA patients' cognitive profile was confirmed as mainly attentional/executive, a complex cognitive profile, characterized also by deficit in semantic memory, seems the hallmark of CAA patients.

Changes in an in-vivo classifier of ARTerioloSclerosis (ARTS) with simultaneous change in cognition for older African Americans.

At autopsy, African American decedents often have mixed Alzheimer's and cerebrovascular brain pathologies including arteriolosclerosis. We applied a novel in-vivo classifier of ARTerioloSclerosis (ARTS) in 167 older African Americans (∼75y of age) with > 2 biennial 3 T MRI scans and > 3 years of associated cognitive follow-up to determine if ARTS scores (higher score=higher likelihood of arteriolosclerosis) changed over time and if this change associated with changes in cognition in the same individuals. Mixed effects regression models tested whether ARTS scores increased over time, while simultaneous mixed effects regression models estimated the simultaneous rates of change in both ARTS and cognition and the correlation of these changes. ARTS scores increased over time (estimate=0.030, SE=0.002, p < 0.0001). Faster increases in ARTS were associated with faster rates of global cognitive decline (r = -0.447, p = 0.006) and domain-specific cognitive functions. Applying an in-vivo marker of arteriolosclerosis in an African American cohort revealed that the likelihood of arteriolosclerosis increases over time, and participants whose ARTS scores increased more rapidly tended to have faster than average rates of cognitive decline.

Serum levels of sonic hedgehog in patients with IgA nephropathy are closely associated with intrarenal arteriolar lesions.

BACKGROUND: Intrarenal arteriolar disease is a major risk factor for poor prognosis in immunoglobulin A nephropathy (IgAN). The morphologic factor sonic hedgehog (SHH) plays an important role in a variety of vascular diseases, so it may be directly or indirectly involved in the process of renal arteriolar disease. The purpose of this study was to investigate the correlation between serum SHH levels and renal arteriole disease in patients with IgAN. METHODS: Subjects with primary IgAN diagnosed by renal biopsy performed between October 2018 and August 2019 at the First Medical Center of the Chinese PLA General Hospital were recruited. Blood specimens were collected from the patients within 1 week before renal biopsy after they signed an informed consent form, and healthy controls were recruited for blood specimen collection during the same period. The concentration of serum SHH was measured by enzyme-linked immunosorbent assay in this population. RESULTS: Serum SHH levels were significantly lower in the IgAN group than in the control group. 41 of the 94 subjects diagnosed with IgAN had severe renal arteriolosclerosis and, compared to their less severely affected counterparts, were older, more hypertensive, and characterized by lower levels of SHH, higher levels of tubular atrophy/interstitial fibrosis and a higher Lee's classification. Serum SHH concentration was found to be an independent predictor of severe intrarenal arteriolosclerosis in IgAN subjects after correction using multivariate analysis. CONCLUSION: In this study, serum SHH levels were found to be significantly lower in patients with IgAN than in healthy subjects. Serum SHH may serve as a noninvasive biomarker of intrarenal arteriolosclerosis in patients with IgAN.

Using digital pathology to analyze the murine cerebrovasculature.

Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and cross-reactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed sections. A panel of immunohistochemical blood vessel markers were tested (including CD31, CD34, collagen IV, DP71, and VWF), to evaluate their suitability for digital pathological analysis. Collagen IV provided the best immunostaining results in both FFPE and frozen fixed murine brain sections, with highly-specific staining of large and small blood vessels and low background staining. Subsequent analysis of collagen IV-stained sections showed region and sex-specific differences in vessel density and vessel wall thickness. We conclude that digital pathology provides a useful tool for relatively unbiased analysis of the murine cerebrovasculature, provided proper protein markers are used.

Clinical characteristics of Martorell hypertensive ischaemic leg ulcer.

OBJECTIVE: We sought to characterise the clinical picture of Martorell hypertensive ischaemic leg ulcer (HYTILU) by describing the ulcer borders with three clinical features: 'the red lipstick sign'; purple border; and livedo racemosa. We also aimed to characterise comorbidities and determinants of healing time. METHOD: A single-centre, retrospective cohort study was conducted between 2015-2020. We scrutinised ulcer photographs for relevant clinical signs. Data on comorbidities, medication and ulcer treatments, as well as method of diagnosis and healing time, were collected from patients' electronic medical records. RESULTS: In total, 38 female patients and 31 male patients (mean age 73 years) were assessed, with a mean follow-up time of 174 days. The 'red lipstick-like' margin covered 0-50% of the ulcer margin in 56.5% of the ulcers, and 51-100% of the ulcer margin in 43.5% of the ulcers. Purple border or livedo racemosa was observed in 70.5% of the ulcers. All patients had hypertension and 52.2% of patients had type 2 diabetes. A heavy cardiovascular disease burden and frequent concomitant vascular pathologies were found. Infections requiring systemic antibiotics, ulcer size and duration of symptoms before diagnosis were strongly associated with healing time. We also found that use of systemic corticosteroids and severity of hypertension (measured by the number of antihypertensive medications used) delayed healing. CONCLUSION: Our data suggest that 'the red lipstick sign' could be a novel diagnostic feature in HYTILUs alongside purple border, livedo racemosa and necrotic/fibrinous ulcer bed. The results also elucidated HYTILU comorbidities, and showed that infections and delay in diagnosis impeded healing.

Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer's disease.

Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large and small vessels and is a key driver of age-related cognitive decline. Severe VCID includes post-stroke dementia, subcortical ischemic vascular dementia, multi-infarct dementia, and mixed dementia. While VCID is acknowledged as the second most common form of dementia after Alzheimer's disease (AD) accounting for 20% of dementia cases, VCID and AD frequently coexist. In VCID, cerebral small vessel disease (cSVD) often affects arterioles, capillaries, and venules, where arteriolosclerosis and cerebral amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent small subcortical infarcts, lacunes of presumed vascular origin, enlarged perivascular space, microbleeds, and brain atrophy are neuroimaging hallmarks of cSVD. The current primary approach to cSVD treatment is to control vascular risk factors such as hypertension, dyslipidemia, diabetes, and smoking. However, causal therapeutic strategies have not been established partly due to the heterogeneous pathogenesis of cSVD. In this review, we summarize the pathophysiology of cSVD and discuss the probable etiological pathways by focusing on hypoperfusion/hypoxia, blood-brain barriers (BBB) dysregulation, brain fluid drainage disturbances, and vascular inflammation to define potential diagnostic and therapeutic targets for cSVD.

The Association of Smoking and Hyperuricemia with Renal Arteriolosclerosis in IgA Nephropathy.

The combination effects of smoking (SMK) and hyperuricemia (HU) on renal arteriolosclerosis in patients with IgA nephropathy remain unknown. We examined the cross-sectional association between smoking (current or former) and renal arteriolar hyalinosis and wall thickening with or without HU [uric acid (UA) level ≥ 7 and ≥5 mg/dL in men and women] in 87 patients with IgA nephropathy who underwent renal biopsy. Arteriolar hyalinosis and wall thickening were assessed by the semiquantitative grading of arterioles. The SMK/HU subgroup showed the highest indices for hyalinosis and wall thickening, followed by the non-SMK/HU, SMK/non-HU, and non-SMK/non-HU subgroups. Multiple logistic analysis showed that SMK/HU, but not SMK/non-HU, was significantly associated with an increased risk of higher-grade renal arteriolar wall thickening. However, this did not occur with hyalinosis compared to non-SMK/non-HU. The adjusted odds ratio (95% confidence interval, p value) for SMK/HU was 12.8 (1.36-119, p < 0.05) for wall thickening. An association between SMK and renal arteriolar wall thickening might be prevalent only among patients with HU and in patients with IgA nephropathy. Further prospective studies are needed to determine whether patients with HU and SMK history exhibit rapid eGFR deterioration.

Characterization of hippocampal sclerosis of aging and its association with other neuropathologic changes and cognitive deficits in the oldest-old.

Hippocampal sclerosis of aging (HS-A) is a common age-related neuropathological lesion characterized by neuronal loss and astrogliosis in subiculum and CA1 subfield of hippocampus. HS-A is associated with cognitive decline that mimics Alzheimer's disease. Pathological diagnosis of HS-A is traditionally binary based on presence/absence of the lesion. We compared this traditional measure against our novel quantitative measure for studying the relationship between HS-A and other neuropathologies and cognitive impairment. We included 409 participants from The 90+ study with neuropathological examination and longitudinal neuropsychological assessments. In those with HS-A, we examined digitized H&E and LFB stained hippocampal slides. The length of HS-A in each subfield of hippocampus and subiculum, each further divided into three subregions, was measured using Aperio eSlide Manager. For each subregion, the proportion affected by HS-A was calculated. Using regression models, both traditional/binary and quantitative measures were used to study the relationship between HS-A and other neuropathological changes and cognitive outcomes. HS-A was present in 48 (12%) of participants and was always focal, primarily affecting CA1 (73%), followed by subiculum (9%); overlapping pathology (subiculum and CA1) affected 18% of individuals. HS-A was more common in the left (82%) than the right (25%) hemisphere and was bilateral in 7% of participants. HS-A traditional/binary assessment was associated with limbic-predominant age-related TDP-43 encephalopathy (LATE-NC; OR = 3.45, p < 0.001) and aging-related tau astrogliopathy (ARTAG; OR = 2.72, p = 0.008). In contrast, our quantitative approach showed associations between the proportion of HS-A (CA1/subiculum/combined) and LATE-NC (p = 0.001) and arteriolosclerosis (p = 0.005). While traditional binary assessment of HS-A was associated with impaired memory (OR = 2.60, p = 0.007), calculations (OR = 2.16, p = 0.027), and orientation (OR = 3.56, p < 0.001), our quantitative approach revealed additional associations with impairments in language (OR = 1.33, p = 0.018) and visuospatial domains (OR = 1.37, p = 0.006). Our novel quantitative method revealed associations between HS-A and vascular pathologies and impairment in cognitive domains that were not detected using traditional/binary measures.

Association of Apolipoprotein E4-related Microvascular Disease in the Alzheimer's Disease Hippocampal CA1 Stratum Radiatum.

Current data suggest a hypothesis of vascular pathogenesis for the development and progression of Alzheimer's disease (AD). To investigate this, we studied the association of apolipoprotein E4 (APOE4) gene on microvessels in human autopsy-confirmed AD with and without APOE4, compared with age/sex-matched control (AC) hippocampal CA1 stratum radiatum. AD arterioles (without APOE4 gene) had mild oxidative stress and loss of vascular endothelial growth factor (VEGF) and endothelial cell density, reflecting aging progression. In AD + APOE4, an increase in strong oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), VEGF, and endothelial cell density were associated with increased diameter of arterioles and perivascular space dilation. In cultured human brain microvascular cells (HBMECs), treatment of ApoE4 protein plus amyloid-ß (Aß) oligomers increased superoxide production and the apoptotic marker cleaved caspase 3, sustained hypoxia inducible factor-1α (HIF-1α) stability that was associated with an increase in MnSOD, VEGF, and cell density. This cell over-proliferation was inhibited with the antioxidants N-acetyl cysteine and MnTMPyP, the HIF-1α inhibitor echinomycin, the VEGFR-2 receptor blocker SU1498, the protein kinase C (PKC) ε knock-down (KD) and the extracellular signal-regulated kinase 1/2 (ERK) inhibitor FR180204. The PKCε KD and echinomycin decreased VEGF and/or ERK. In conclusion, AD capillaries and arterioles in hippocampal CA1 stratum radiatum of non-APOE4 carriers are related with aging, while those in APOE4 carriers with AD are related with pathogenesis of cerebrovascular disease.

Relationships between Cerebral Vasculopathies and Microinfarcts in a Community-Based Cohort of Older Adults.

Cerebral microinfarcts are associated with cognitive impairment and dementia. Small vessel diseases such as cerebral arteriolosclerosis and cerebral amyloid angiography (CAA) have been found to be associated with microinfarcts. Less is known about the associations of these vasculopathies with the presence, numbers, and location of microinfarcts. These associations were examined in the clinical and autopsy data of 842 participants in the Adult Changes in Thought (ACT) study. Both vasculopathies were categorized by severity (none, mild, moderate, and severe) and region (cortical and subcortical). Odds ratios (OR) and 95% CIs for microinfarcts associated with arteriolosclerosis and CAA adjusted for possible modifying covariates such as age at death, sex, blood pressure, APOE genotype, Braak, and CERAD were estimated. 417 (49.5%) had microinfarcts (cortical, 301; subcortical, 249), 708 (84.1%) had cerebral arteriolosclerosis, 320 (38%) had CAA, and 284 (34%) had both. Ors (95% CI) for any microinfarct were 2.16 (1.46-3.18) and 4.63 (2.90-7.40) for those with moderate (n = 183) and severe (n = 124) arteriolosclerosis, respectively. Respective Ors (95% CI) for the number of microinfarcts were 2.25 (1.54-3.30) and 4.91 (3.18-7.60). Similar associations were observed for cortical and subcortical microinfarcts. Ors (95% Cis) for the number of microinfarcts associated with mild (n = 75), moderate (n = 73), and severe (n = 15) amyloid angiopathy were 0.95 (0.66-1.35), 1.04 (0.71-1.52), and 2.05 (0.94-4.45), respectively. Respective Ors (95% Cis) for cortical microinfarcts were 1.05 (0.71-1.56), 1.50 (0.99-2.27), and 1.69 (0.73-3.91). Respective Ors (95% Cis) for subcortical microinfarcts were 0.84 (0.55-1.28), 0.72 (0.46-1.14), and 0.92 (0.37-2.28). These findings suggest a significant association of cerebral arteriolosclerosis with the presence, number, and location (cortical and subcortical) of microinfarcts, and a weak and non-significant association of CAA with each microinfarct, highlighting the need for future research to better understand the role of small vessel diseases in the pathogenesis of cerebral microinfarcts.

Pathological Changes of Small Vessel Disease in Intracerebral Hemorrhage: a Systematic Review and Meta-analysis.

In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral amyloid angiopathy (CAA) and arteriolosclerosis, and directly compared MRI and pathological changes of markers of cerebral small vessel disease (CSVD). Studies enrolling primary ICH who had received an etiological diagnosis through biopsy or autopsy were searched using Ovid MEDLINE, PubMed, and Web of Science from inception to June 8, 2022. We extracted pathological changes of CSVD for each patient whenever available. Patients were grouped into CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis subgroups. Of 4155 studies identified, 28 studies with 456 ICH patients were included. The frequency of lobar ICH (p<0.001) and total microbleed number (p=0.015) differed among patients with CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis. Concerning pathology, severe CAA was associated with arteriolosclerosis (OR 6.067, 95% CI 1.107-33.238, p=0.038), although this association was not statistically significant after adjusting for age and sex. Additionally, the total microbleed number (median 15 vs. 0, p=0.006) was higher in ICH patients with CAA evidence than those without CAA. The pathology of CSVD imaging markers was mostly investigated in CAA-ICH. There was inconsistency concerning CAA severity surrounding microbleeds. Small diffusion-weighted imaging lesions could be matched to acute microinfarct histopathologically. Studies that directly correlated MRI and pathology of lacunes, enlarged perivascular spaces, and atrophy were scarce. Arteriolosclerosis might be associated with severe CAA. The pathological changes of CSVD markers by ICH etiology are needed to be investigated further.

Locus coeruleus pathology is associated with cerebral microangiopathy at autopsy.

INTRODUCTION: We investigated the link between locus coeruleus (LC) pathology and cerebral microangiopathy in two large neuropathology datasets. METHODS: We included data from the National Alzheimer's Coordinating Center (NACC) database (n = 2197) and Religious Orders Study and Rush Memory and Aging Project (ROSMAP; n = 1637). Generalized estimating equations and logistic regression were used to examine associations between LC hypopigmentation and presence of cerebral amyloid angiopathy (CAA) or arteriolosclerosis, correcting for age at death, sex, cortical Alzheimer's disease (AD) pathology, ante mortem cognitive status, and presence of vascular and genetic risk factors. RESULTS: LC hypopigmentation was associated with higher odds of overall CAA in the NACC dataset, leptomeningeal CAA in the ROSMAP dataset, and arteriolosclerosis in both datasets. DISCUSSION: LC pathology is associated with cerebral microangiopathy, independent of cortical AD pathology. LC degeneration could potentially contribute to the pathways relating vascular pathology to AD. Future studies of the LC-norepinephrine system on cerebrovascular health are warranted. HIGHLIGHTS: We associated locus coeruleus (LC) pathology and cerebral microangiopathy in two large autopsy datasets. LC hypopigmentation was consistently related to arteriolosclerosis in both datasets. LC hypopigmentation was related to cerebral amyloid angiopathy (CAA) presence in the National Alzheimer's Coordinating Center dataset. LC hypopigmentation was related to leptomeningeal CAA in the Religious Orders Study and Rush Memory and Aging Project dataset. LC degeneration may play a role in the pathways relating vascular pathology to Alzheimer's disease.

Association of vascular and degenerative brain pathologies and past medical history from the National Alzheimer's Coordinating Center Database.

The relationship between past medical histories (PMH) and dementia-related neuropathologies is not well understood. Using the National Alzheimer's Coordinating Center (NACC) database, we explored the relationship between patient-reported PMH and various vascular and degenerative neuropathologies. We examined the following PMH: transient ischemic attack (TIA), stroke, traumatic brain injury, seizures, hypertension, cardiovascular events, hypercholesterolemia, B12 deficiency, diabetes mellitus, and thyroid disease. We dichotomized the following neuropathologies: atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy (CAA), Alzheimer disease neuropathology (ADNP), Lewy bodies (LB), hippocampal sclerosis, frontotemporal lobar degeneration (FTLD), and TAR DNA-binding protein-43 (TDP-43). Separate logistic regression models assessed the relationship between the outcome of individual neuropathologies and all PMHs. Additional logistic regressions were stratified by sex to further examine these associations. Hypertension history was associated with an increased likelihood of atherosclerosis (OR = 1.7) and arteriolosclerosis (OR = 1.3), but decreased odds of ADNP (OR = 0.81), CAA (OR = 0.79), and LB (OR = 0.78). History of TIA was associated with an increased likelihood of atherosclerosis (OR = 1.3) and arteriolosclerosis (OR = 1.4) and lower odds of ADNP (OR = 0.72). Seizure history was associated with an increased likelihood of ADNP (OR = 1.9) and lower odds of FTLD (OR = 0.49). Hypertension history was associated with a greater likelihood of vascular pathologies yet a lower likelihood of ADNP and other neurodegenerative pathologies.

Can novel CT-and MR-based neuroimaging biomarkers further improve the etiological diagnosis of lobar intra-cerebral hemorrhage?

Lobar hematomas represent around half of all supratentorial hemorrhages and have high mortality and morbidity. Their management depends on the underlying cause. Apart from local causes such as vascular malformation, which are rare and can usually be easily excluded thanks to imaging, the vast majority of lobar hematomas equally frequently result from either hypertensive arteriolopathy (HA) or cerebral amyloid angiopathy (CAA). Distinguishing between CAA and HA is important for prognostication (risk of recurrence nearly sevenfold higher in the former), for decision-making regarding, e.g., antithrombotic therapies (for other indications) and for clinical trials of new therapies. Currently, a non-invasive diagnosis of probable CAA can be made using the MR-based modified Boston criteria, which have excellent specificity but moderate sensitivity against histopathological reference, leading to the clinically largely irrelevant diagnosis of "possible CAA". Furthermore, the Boston criteria cannot be applied when both lobar and deep MRI hemorrhagic markers are present, a not uncommon situation. Here we propose to test whether new CT and MR-based imaging biomarkers, namely finger-like projections of the hematoma and adjacent subarachnoid hemorrhage on acute-stage CT or MRI, and remote punctate diffusion-weighted imaging ischemic lesions on acute or subacute-stage MRI, have the potential to improve the performance of the Boston criteria. Furthermore, we also propose to test whether clinical-radiological biomarkers may also allow a positive diagnosis of HA to be made in lobar hematomas, which, if feasible, would not only further reduce the prevalence of "possible CAA" but also permit a diagnosis of HA and/or CAA to be made in the presence of mixed deep and lobar MRI hemorrhagic markers.

Clinicopathological features and prognosis of IgA nephropathy with renal arteriolosclerosis / 中华肾脏病杂志

The study was a retrospective study. The clinical data of 866 patients with IgA nephropathy (IgAN) in Beijing Anzhen Hospital, Capital Medical University from March 2010 to March 2021 were analyzed, to investigate the clinical pathology and renal prognosis of IgAN patients with intrarenal arteriolosclerosis, and to preliminarily explore whether abnormal activation of complement system is involved in the injury of arteriolosclerosis. The patients were divided into renal arteriolar lesions group and non-renal arteriolar lesions group according to the renal histopathology, and the differences of clinical pathological manifestations, prognosis between the two groups were compared. The results showed that, compared with the non-renal arteriolar lesions group ( n=236), IgAN patients in the renal arteriolar lesions group ( n=630) had higher proportions of hypertension and malignant hypertension, higher levels of urinary albumin-creatinine ratio, 24-hour urine protein quantification and serum uric acid, lower estimated glomerular filtration rate, and more severe MEST-C lesions of the Oxford classification (all P < 0.05). Cox regression analysis results showed that intrarenal arteriolosclerosis was the independent risk factor affecting the progression of IgAN to ESRD ( HR=6.437, 95% CI 2.013-20.585, P=0.002). Renal histopathology showed that the deposition of complement C3c on the wall of intrarenal arterioles in the renal arteriolar lesions group ( n=98) was stronger than that in non-renal arteriolar lesions group ( n=18, P < 0.05). IgAN patients with renal arteriolosclerosis present with serious clinical and pathological manifestations, and renal prognosis. Abnormal activation of complement system may be involved in the pathogenesis of intrarenal arteriolosclerosis.

Arteriolosclerosis differs from venular collagenosis in relation to cerebrovascular parenchymal damages: an autopsy-based study.

BACKGROUND AND PURPOSE: Cerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of sclerotic arterioles, the correlation between collagenised venules has not been clarified. Here, we aimed to investigate the associations between microvascular injuries, including arteriolosclerosis and venular collagenosis, and related parenchymal damages in ageing brains, to investigate the underlying correlations. METHODS: We evaluated arteriolosclerosis and venular collagenosis in 7 regions from 27 autopsy cases with no history of stroke or brain tumour. The correlations between the ratio of arteriolosclerosis, venular collagenosis and the severity of cerebrovascular parenchymal damage, including lacunes, microinfarcts, myelin loss, and parenchymal and perivascular haemosiderin deposits, were assessed. RESULTS: Arteriolosclerosis and venular collagenosis became more evident with age. Arteriolosclerosis was associated with lacunes (p=0.004) and brain parenchymal haemosiderin deposits in the superior frontal cortex (p=0.024) but not with leukoaraiosis severity. Venular collagenosis was not associated with the number of lacunes or haemosiderin, while white matter generally became paler with severe venular collagenosis in the periventricular (ß=-0.430, p=0.028) and deep white matter (ß=-0.437, p=0.025). CONCLUSION: Our findings imply an important role for venular lesions in relation to microvessel-related parenchymal damage which is different from that for arteriolosclerosis. Different underlying mechanisms of both cerebral arterioles and venules require further investigation.

Brain and spinal cord arteriolosclerosis and its associations with cerebrovascular disease risk factors in community-dwelling older adults.

Arteriolosclerosis is common in older brains and related to cognitive and motor impairment. We compared the severity of arteriolosclerosis and its associations with cerebrovascular disease risk factors (CVD-RFs) in multiple locations in the brain and spinal cord. Participants (n = 390) were recruited in the context of a longitudinal community-based clinical-pathological study, the Rush Memory and Aging Project. CVD-RFs were assessed annually for an average of 8.7 (SD = 4.3) years before death. The annual assessments included systolic (SBP) and diastolic (DBP) blood pressure, diabetes mellitus (DM), low- and high-density lipoprotein cholesterol, triglyceride, body mass index, and smoking. Postmortem pathological assessments included assessment of arteriolosclerosis severity using the same rating scale in three brain locations (basal ganglia, frontal, and parietal white matter regions) and four spinal cord levels (cervical, thoracic, lumbar and sacral levels). A single measure was used to summarize the severity of spinal arteriolosclerosis assessments at the four levels due to their high correlations. Average age at death was 91.5 (SD = 6.2) years, and 73% were women. Half showed arteriolosclerosis in frontal white matter and spinal cord followed by parietal white matter (38%) and basal ganglia (27%). The severity of arteriolosclerosis in all three brain locations showed mild-to-moderate correlations. By contrast, spinal arteriolosclerosis was associated with brain arteriolosclerosis only in frontal white matter. Higher DBP was associated with more severe arteriolosclerosis in all three brain locations. DM was associated with more severe arteriolosclerosis only in frontal white matter. Controlling for DBP, higher SBP was inversely associated with arteriolosclerosis in parietal white matter. Blood cholesterol and triglyceride, high body mass index, or smoking were not related to the severity of arteriolosclerosis in any brain region. None of the CVD-RFs were associated with the severity of spinal arteriolosclerosis. These data indicate that severity of arteriolosclerosis and its associations with CVD-RFs may vary in different CNS locations.