Cerebral Microangiopathy Research Articles

Cerebral damage after malignant hypertensive crisis: cerebral MRI follow-up data

Abstract Background Malignant hypertension (MHT) crisis is characterized by acute and diffuse microvascular damages, and the brain is a primary target organ. While a recent MRI study has revealed extensive and frequent cerebral injuries during the acute phase of MHT crisis (1), there is a scarcity of follow-up data. Purpose This study aims to investigate the evolution of MRI markers of cerebral injury following the management of the acute phase of MHT. Methods In this retrospective analysis, we examined brain MRI data from patients admitted for acute MHT between 2008 and 2022 at our center. Eligible patients had at least one follow-up brain MRI available. A skilled operator conducted a comprehensive analysis of each brain MRI, searching for posterior reversible encephalopathy syndrome (PRES), acute stroke or cerebral hemorrhage and microangiopathy markers, blinded for clinical and demographical data. Results Among 149 patients enrolled, 104 had a brain MRI at inclusion, 47 individuals had at least one follow-up brain MRI and were included in the analysis. 72,3% were male, mean age was 48,2 ± 10.8 years and 45,7% presented blood pressure control at the time of the follow-up brain MRI. Median interval between initial and follow-up brain MRI was 228 (84 – 726) days. Five (10,6%) new recent strokes, 2 (4,3 %) cerebral hemorrhage and 0 PRES were recorded during follow-up. On the follow-up brain MRI, more patients presented chronic lacunar infarct and/or microbleeds, in higher numbers. On the contrary, overall Fazekas score was stable in 31 patients (66,0%), improved in 15 patients (31,9 %) and worsened in 1 patients (2,1%). Comparison of subgroups dichotomized according to blood pressure control or follow up duration showed no difference in brain MRI markers. Conclusion This study offers valuable insights into the risk of new cerebrovascular events and the evolution of brain MRI markers after managing the acute phase of MHT. Our findings emphasize the dynamic nature of cerebral microvascular burden and the potential for regression of white matter hyperintensities. A better understanding of these phenomena might contribute to improved diagnosis, tailored treatment, and proactive patient care in the context of MHT.

Neurological and Psychiatric Adverse Events Associated with Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer Patients: Insights from a Pharmacovigilance Study via the FDA Adverse Event Reporting System.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have revolutionised cancer therapy, particularly breast cancer therapy. However, concerns about their potential to cause neurological and psychiatric adverse events (AEs) have emerged, and these concerns remain underexplored. This study aimed to investigate the signals related to neurological and psychiatric AEs associated with CDK4/6 inhibitor use. A retrospective study was performed to analyse reports of AEs associated with the use of CDK4/6 inhibitors (abemaciclib, ribociclib and palbociclib) from the first quarter of 2015 to the fourth quarter of 2023 on the basis of the FDA Adverse Event Reporting System (FAERS). Both the reporting odds ratio (ROR) and the multi-item gamma Poisson shrinker (MGPS) were used for signal detection. The timing of events was assessed with the Weibull shape parameter (WSP). The management, analysis and presentation of the data were performed via Python (version 3.8) and R software (version 4.3.2). A total of 19,001 AE reports in which CDK4/6 inhibitors were identified as the 'primary suspect drug' were included in this study. These events were predominantly observed in patients aged 65 to 85 years. Through an ROR analysis, 85 positive signals for neurological and psychiatric AEs associated with CDK4/6 inhibitors were identified. The MGPS method revealed 61 positive AE signals for neurological and psychiatric AEs associated with CDK4/6 inhibitors. A total of 34 positive AE signals were identified by both the ROR and MGPS analyses. The WSP indicated that the onset times for AEs associated with all three CDK4/6 inhibitors tended to be early in drug therapy, suggesting a propensity for early failuretype. The present study revealed neurological and psychiatric AEs associated with CDK4/6 inhibitors that often occur early in treatment. Significant signals include spinal cord herniation and cerebral microangiopathy. Close monitoring of these AEs is crucial. Further studies are necessary to verify the connection between CDK4/6 inhibitors and neurological and psychiatric AEs.

Assessment of retinal arteriolar tortuosity in patients with COL4A1 or COL4A2 mutations.

Qualitative and quantitative analyzes of retinal arteriolar tortuosity (RAT) in patients with COL4A1 and COL4A2 mutations to identify a tortuosity index (TI) threshold for detecting increased RAT. Fifty-two eyes of 28 patients were included. Group 1 included eyes with a normal arteriolar pattern (n=19, 37%), group 2 included eyes with moderately increased arteriolar tortuosity (n=13, 25%), and group 3 included eyes with typical abnormal arteriolar tortuosity (n=20, 38%). The TI was measured by calculating the arc-to-chord ratio of arterioles and venules in the posterior pole. The mean arteriolar TI was significantly higher in all groups with a COL4A1/A2 mutation compared to controls: 1.19 ± 0.03, 1.24 ±0.05, and 1.57 ± 0.23 in groups 1, 2 and 3, respectively, vs. 1.12 ± 0.01 (all p <0.0001). The TI threshold was 1.13, with a sensitivity of 98.1% and a specificity of 100%. The area under the curve was 0.995. Measuring the arteriolar TI allowed diagnosing increased RAT in all eyes with a COL4A1/A2 mutation, whereas the subjective assessment suspected or detected it in only 62% of eyes. In adult patients with cerebral microangiopathy, detecting increased RAT, even when mild, directs the diagnosis towards COL4A1/A2-related cerebroretinal angiopathy.

Teaching NeuroImage: Porencephaly and Hemorrhage in Infantile COL4A2-Related Cerebral Microangiopathy.

Teaching NeuroImage: Porencephaly and Hemorrhage in Infantile COL4A2-Related Cerebral Microangiopathy.

Left atrial appendage closure in patients with atrial fibrillation and acute ischaemic stroke despite anticoagulation

BackgroundThe occurrence of acute ischaemic stroke (AIS) while using oral anticoagulants (OAC) is an increasingly recognised problem among nonvalvular atrial fibrillation (NVAF) patients. We aimed to elucidate the potential role...

The central vein sign in the diagnosis of multiple sclerosis

Objective: to determine the specificity and sensitivity of the central vein sign (CVS) for the diagnosis of multiple sclerosis (MS). Material and methods. We analyzed 76 patients. The main group consisted of 40 patients with a confirmed diagnosis of MS according to the McDonald criteria, 2017. The comparison group included 20 patients with migraine and 16 patients with cerebral microangiopathy. All patients underwent a standardized MRI scan of the brain, including 3D FLAIR and SWI modes. The total number of T2/FLAIR hyperintense lesions in the brain and the number of lesions with CVS were calculated. Results. In the group of MS patients, the total and relative number of lesions with CVS was higher than in the comparison group (p&lt;0.001). The 40% lesion rule had a sensitivity of 97.5% and a specificity of 94.4%. The sensitivity of the 3-lesion rule was 92.5% and the specificity 66.7%. The use of the 5-lesion rule had a sensitivity of 75% and a specificity of 83.7%. Conclusion. The data obtained indicate a significant diagnostic role for SCV in MS. The use of the 5-lesion rule provides high sensitivity and specificity with relative ease of use.

Hydroxychloroquine Use is Associated with Decreased Prevalence of Cerebral Microangiopathy in Patients with Systemic Lupus Erythematosus (S34.006)

Hydroxychloroquine Use is Associated with Decreased Prevalence of Cerebral Microangiopathy in Patients with Systemic Lupus Erythematosus (S34.006)

Age-Dependent Cerebral Microangiopathy Associated with Vascular Risk Factors: How to Recognize the Signs?

The focus of this article is on cerebral microangiopathy (CMA), also known as cerebral small vessel disease, which is commonly linked to age and vascular risk factors. It is a major contributor to both vascular and mixed cognitive decline in older individuals. The leading causes of vascular cognitive impairment and dementia include hypertension, high cholesterol, type 2 diabetes mellitus, smoking, and atrial fibrillation. The main manifestations of CMA in patients over 60 are outlined in this article, with supporting evidence from both domestic and foreign studies. By examining a specific clinical case, the characteristics, diagnosis, and treatment of cognitive impairment caused by CMA and vascular risk factors in an older patient were analyzed.

Correlation analysis between cerebral microangiopathy and autonomic nervous dysfunction.

Our study was conducted aimed at investigating the potential correlation between cerebral microangiopathy and autonomic nervous dysfunction. We initially included 164 hospitalized patients with cerebral microangiopathy at our hospital from November 2019 to January 2021. Based on the inclusion and exclusion criteria, a final total of 162 patients with cerebral microangiopathy were selected. According to the patient's Autonomic Symptom Profile (ASP) score, patients with a score greater than 22 were categorized into a group with concomitant autonomic dysfunction (71 cases, combined group), while those with a score below 22 were categorized into a group of isolated cerebral microangiopathy (83 cases, cerebral microangiopathy group). The general data and laboratory examination results of the two groups were analyzed, and Pearson correlation analysis was performed to evaluate the correlation between cerebral microangiopathy and autonomic dysfunction, as well as the influencing factors of cerebral microangiopathy patients combined with autonomic dysfunction. There were no significant differences between the two groups in terms of sex, BMI, smoking, drinking, family dementia history, diabetes, hypothyroidism, carotid atherosclerosis, obstructive sleep apnea hypopnea syndrome, hyperuricemia, hyperlipidemia, chronic obstructive pulmonary disease, Hamilton Anxiety Scale score, Hamilton Depression Scale score, 24-h mean systolic blood pressure (SBP), 24-h mean diastolic blood pressure DBP, daytime mean systolic blood pressure (dSBP), daytime mean diastolic blood pressure, nighttime mean systolic blood pressure (nSBP), nighttime mean diastolic blood pressure, 24-h systolic blood pressure standard deviation (SBPSD), 24-h diastolic blood pressure standard deviation, daytime diastolic blood pressure standard deviation, nighttime diastolic blood pressure standard deviation (nDBPSD), nDBPSD (p>.05). However, significant differences were observed between the two groups regarding age, history of coronary heart disease, hypertension, leukoaraiosis, cognitive function, ASP score, SSR, 24-h SBPSD, daytime systolic blood pressure standard deviation (dSBPSD), nighttime systolic blood pressure standard deviation (nSBPSD), standard deviation of RR interval (SDNN), root mean square value of successive RR interval difference (RMSSD), high-frequency component (HF), and low-frequency component (LF) (p<.05). Moreover, the levels of TG, TC, HDL-C, and LDL-C did not show significant differences between the two groups (p>.05), but there were significant differences in blood uric acid and homocysteine (Hcy) levels (p<.05). Age, history of leukoaraiosis, cognitive function assessment, blood uric acid, Hcy levels, 24-h SBPSD, dSBPSD, and nSBPSD showed positive correlations with ASP scores and SSR in patients with cerebral microangiopathy (p<.001). In contrast, hypertension, SDNN, RMSSD, HF, and LF showed negative correlations with ASP scores and SSR (p<.001). Moreover, coronary heart disease was negatively correlated with ASP scores but positively correlated with SSR (p<.001). The independent variables included age, history of leukoaraiosis, cognitive function assessment, ASP score, SSR, blood uric acid, Hcy, bradykinin, coronary heart disease, hypertension, 24-h SBPSD, dSBPSD, nSBPSD, SDNN, RMSSD, HF, and LF, which were indicators with differences in general data and laboratory indicators. The dependent variable was patients with cerebral microangiopathy combined with autonomic nervous dysfunction. The analysis results showed that age, history of leukoaraiosis, ASP score, SSR, 24-h SBPSD, dSBPSD, nSBPSD, SDNN, RMSSD, HF, and LF were the influencing factors of patients with cerebral microangiopathy complicated with autonomic nervous dysfunction. We demonstrates that age, history of leukoaraiosis, cognitive function assessment, blood uric acid, Hcy level, 24-h SBPSD, dSBPSD, nSBPSD, blood pressure, SDNN, RMSSD, HF, LF, and coronary heart disease were highly associated with cerebral microangiopathy with autonomic dysfunction. Furthermore, the influencing factors of cerebral microangiopathy with autonomic dysfunction are age, history of leukoaraiosis, ASP score, SSR, blood pressure variability, and HRV.

Abstract WP122: Statins May Increase White Matter Hyperintensity Burden in Older Adults: A Systematic Review and Meta-Analysis

Introduction: White matter hyperintensities (WMH) are a hallmark radiographic finding of cerebral microangiopathy. Longitudinal studies have shown varying effects of statins on accrual of WMH over time. We aimed to understand the impact of statins on WMH volume over time through a systematic review and meta-analysis. Methods: We performed a systematic review using standard search and risk of bias assessment practices. We included statin-exposed and statin-naive adults with longitudinal brain MRIs with computer-generated WMH volumetric analyses. The primary outcome was change in WMH volume (mL). Allowing for curvilinear change, a mixed-effects model was applied to capture the dynamic change over time. Model forecasts were used to visualize results, comparing changes over time among younger cohorts (60 years) and older cohorts (75 years) based on the the cohort mean age standard deviation. A p value ≤ 0.05 was considered significant. Results: We identified 6 studies enrolling 1911 participants from China, Europe, and North America (2 studies each); mean age 67.5 (± 7.5). The maximal study duration was 60-months. All studies had a least some degree of bias. Control groups had steady increase in WMH volume over time, Figures. The younger statin-exposed cohort developed statistically less WMH after 40 months of use. Older statin exposed patients had an increase in WMH volume compared with naïve patients which remained over the study duration. Conclusion: The impact of statins on WMH volume may be age dependent whereby older patients may have an accelerated accumulation. Further studies are warranted to confirm this data and investigate underlying mechanisms leading to this finding.

Modern understanding of the pathogenetic mechanisms of small vessel disease

Cerebrovascular pathology occupies the leading position among the causes of mortality and long-term disability in high-, middle- and low-income countries, which indicates the extreme relevance of finding new strategies for the prevention of these diseases. Today, acute ischemic stroke and vascular cognitive disorders, including vascular dementia, are among the most common forms of cerebrovascular diseases. Damage to cerebral small vessels plays a significant role in the pathogenesis of both conditions. The article analyzed literature data on the main and probable pathogenetic mechanisms of cerebral small vessel disease. Keywords used to select the literature in PubMed National Library of Medicine included: small vessel disease, white matter hyperintensity, lacunae, enlarged perivascular spaces, brain atrophy, vascular cognitive disorders. The study of the pathogenetic mechanisms of cerebral microangiopathy or cerebral small vessel disease will allow clinical and scientific research to be directed to the search for pathogenetically justified treatment and prevention strategies, which is extremely important for such patients.

Когнитивные нарушения у мужчин с церебральной микроангиопатией и возрастным гипогонадизмом

Cognitive function impairment is one of the main disabling manifestations of vascular and degenerative brain pathology. The main cause of vascular dementia is cerebral microangiopathy (CMA) caused by arterial hypertension. The existing gender differences in the age of onset of cerebral vascular pathology in men increasingly draw researchers’ attention to the problem of age-related decline in gonadal function. The high association of metabolic risk factors for cardiovascular diseases with age-related hypogonadism (AHG) and the prospects of its correction determined our interest in the study of cognitive functions in adult men. The purpose was to investigate the structure and severity of cognitive disorders in patients with CMA and AHG. Material and methods. We performed an in-depth neuropsychological testing of 171 men aged 45 to 60 years with complaints of memory and attention impairment against the background of CMA and 52 practically healthy individuals without cerebral complaints (control group). Based on clinical and laboratory assessment of sexual function, patients with CMA were divided into groups: group 1 with AHG (74 persons) and group 2 without it (77 persons). Results. The examined men did not differ in age, education, behavioral disorders, stress level, Apo E 4 allele carrier both in the main and comparison groups; the manifestations of metabolic syndrome and CMA in men with AHG were more expressed than in men with normal gonadal function. Psychometric studies revealed impairment of frontal-executive functions both in isolation and in combination with other cognitive disorders (multifunctional type of moderate cognitive disorders) significantly more often in hypogonadal men. Conclusions. Complaints of cognitive decline in men with cerebral microangiopathy should promote the efforts of physicians to search for AHG in order to correct it and prevent cognitive impairment in the future.

Identifying the neurostimulation target for treatment of cognitive impairment in aging and early cerebral small vessel disease

To develop individualized approaches to the use of neuromodulation as a non-pharmacological treatment of cognitive impairment (CI) based on the assessment of compensatory brain reserves in functional MRI (fMRI). Twenty-one adults over 45 years of age, representing a continuum from healthy norm to mild cognitive impairment due to aging and early cerebral small vessel disease, were studied. All participants underwent fMRI while performing two executive tasks - a modified Stroop task and selective counting. To assess the ability to compensate for CI in real life, functional activation and connectivity were analyzed using the BRIEF-MoCA score as a covariate, which is the difference in ratings between the Behavior Rating Inventory of Executive Function (BRIEF) and the Montreal Cognitive Assessment Scale (MoCA). Both fMRI tasks were associated with activation of areas of the frontoparietal control network, as well as supplementary motor area (SMA) and the pre-SMA, the lateral premotor cortex, and the cerebellum. An increase in pre- SMA connectivity was observed during the tasks. The BRIEF-MoCA score correlated firstly with connectivity of the left dorsolateral prefrontal cortex (DLPFC) and secondly with involvement of the occipital cortex during the counting task. The developed technique allows identification of the functionally relevant target within the left DLPFC in patients with CI in aging and early cerebral microangiopathy.

Predicting the risk of progression of cognitive and oxidative impairment in patients with cerebral microangiopathy

Predicting the risk of progression of cognitive and oxidative impairment in patients with cerebral microangiopathy

The Role of Extracellular Matrix and Inflammation in the Stratification of Bleeding and Thrombotic Risk of Atrial Fibrillation on Oral Anticoagulant Therapy: Insights from Strat-Af Study.

In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.

Prevalence and Impact of Cerebral Microbleeds on Clinical and Safety Outcomes in Acute Ischaemic Stroke Patients Receiving Reperfusion Therapy: A Systematic Review and Meta-Analysis.

Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed with acute ischemic stroke (AIS), which is in turn linked to less favourable clinical prognoses. Nevertheless, the exact prevalence of CMBs and their influence on post-reperfusion therapy outcomes remain inadequately elucidated. Through systematic searches of PubMed, Embase and Cochrane databases, studies were identified adhering to specific inclusion criteria: (a) AIS patients, (b) age ≥ 18 years, (c) CMBs at baseline, (d) availability of comparative data between CMB-positive and CMB-negative groups, along with relevant post-reperfusion therapy outcomes. The data extracted were analysed using forest plots of odds ratios, and random-effects modelling was applied to investigate the association between CMBs and symptomatic intracerebral haemorrhage (sICH), haemorrhagic transformation (HT), 90-day functional outcomes, and 90-day mortality post-reperfusion therapy. In a total cohort of 9776 AIS patients who underwent reperfusion therapy, 1709 had CMBs, with a pooled prevalence of 19% (ES 0.19; 95% CI: 0.16, 0.23, p < 0.001). CMBs significantly increased the odds of sICH (OR 2.57; 95% CI: 1.72; 3.83; p < 0.0001), HT (OR 1.53; 95% CI: 1.25; 1.88; p < 0.0001), as well as poor functional outcomes at 90 days (OR 1.59; 95% CI: 1.34; 1.89; p < 0.0001) and 90-day mortality (OR 1.65; 95% CI: 1.27; 2.16; p < 0.0001), relative to those without CMBs, in AIS patients undergoing reperfusion therapy (encompassing intravenous thrombolysis [IVT], endovascular thrombectomy [EVT], either IVT or EVT, and bridging therapy). Variations in the level of association can be observed among different subgroups of reperfusion therapy. This meta-analysis underscores a significant association between CMBs and adverse postprocedural safety outcomes encompassing sICH, HT, poor functional outcome, and increased mortality in AIS patients undergoing reperfusion therapy. The notable prevalence of CMBs in both the overall AIS population and those undergoing reperfusion therapy emphasizes their importance in post-stroke prognostication.

ЦЕРЕБРОВАСКУЛЯРНАЯ ПАТОЛОГИЯ У ПАЦИЕНТОВ C ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА (РЕЗУЛЬТАТЫ НЕЙРОВИЗУАЛИЗАЦИИ)

Introduction. Cerebral microangiopathy associated with vascular risk factors makes a significant contribution to the deterioration of the morphological state of the brain. The aim of the study was to assess the neurological status and state of the brain in patients with stable coronary heart disease (CHD) who are treated in the cardiology department before coronary bypass surgery. Material and methods. 170 male patients, aged 58±6 years, were examined. Patients with a history of acute cerebrovascular accident, trauma and brain masses, carotid artery stenosis &gt;50%, depression and dementia were not included. All of them underwent a neurological examination and testing according to the Mini Mental Status Assessment Scale (MSSS). The brain examination was performed on a multislice computed tomography (MSCT) Somatom Sensation 64, Siemens. In describing the results, the following were taken into account: the width of the ventricles of the brain (the age norm of the width of the third ventricle is &lt;7 mm for persons under 60 years of age, and &lt;9 mm - over 60 years of age), leukoaraiosis, cysts, signs of cortical atrophy, the ventriculocranial index 3 (VKI 3) was calculated - the ratio of the maximum width of the third ventricle to the greatest distance between the internal plates of the skull bones (age norms: persons 41-60 years old - 3.3%; 61-70 years old - 3.9%; over 70 years old - 4.3%). Standard methods of descriptive statistics were used. Results. After a neurological examination, it was found that the frequency of occurrence of vestibulopathy syndrome was 24%, asthenic syndrome - 56%, mild cognitive impairment syndrome - 46% (test results for KShOPS - 27 [26; 28] points). The identified neurological symptoms were accompanied by morphological changes in the brain tissues. The width of the third ventricle was 7.6 ± 2.0 mm, the IHF index was 3 - 4.2%, the number of patients with leukoaraiosis was 26%, with signs of cortical atrophy - 19% of patients. When comparing the obtained results of neuroimaging with the established age norms, it was found that, despite the fact that the average age of our patients did not exceed 60 years, the width of the third ventricle in them corresponded to the indicators of the age category of healthy people over 60 years old, and the values of the VKI 3 index corresponded to the age norms. for healthy subjects over 70 years of age. Conclusion. The data obtained indicate that asthenia, moderate cognitive disorders, disorders of the coordinating-motor sphere are very common in patients with coronary artery disease. Neuroimaging signs of cerebral microangiopathy (leukoareosis, expansion of cerebrospinal fluid spaces) indicate the vascular nature of the identified neurological disorders. Issues of progression of cerebrovascular pathology in this cohort of patients require further study.

COVID-19-related multiple inflammatory syndrome-C and pulmonary embolism in Aicardi-Goutries syndrome.

COVID-19-related multiple inflammatory syndrome-C and pulmonary embolism in Aicardi-Goutries syndrome.

Depression in patients with cerebral microangiopathy

Cerebral microangiopathy (CMA) is one of the significant causes of depression in the elderly. Close associations of the risk of developing depression with white matter hyperintensity, the presence of lacunar infarcts, and other markers of vascular disease are shown. The available data suggest that various vascular mechanisms, in particular, involvement of small vessels of the brain, generalized microvascular and endothelial dysfunction, metabolic risk factors, – are risk factors for the development of depression. Pathogenetic mechanisms include cerebral hypoperfusion and immune dysregulation. Depression is also a common complication of coronavirus infection, occurring both in the acute and postCOVID periods. The same mechanisms as in vascular depression are involved in the pathogenesis of the development of post-COVID depressive disorders. Given the complexity of the mechanisms of development of depressive disorders in patients with CMA, the presence of severe comorbid vascular pathology, antidepressants with an optimal ratio of efficacy and safety should be preferred. Agomelatine (Valdoxan) is one of such drugs.

Locus coeruleus pathology is associated with cerebral microangiopathy at autopsy.

We investigated the link between locus coeruleus (LC) pathology and cerebral microangiopathy in two large neuropathology datasets. 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. 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. 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. 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.