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INTRODUCTION: Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimers disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status. METHODS: TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology. RESULTS: Severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 correlating with abundant arteriolar Aβ40 deposition were identified in MCI and AD patients. Retinal claudin-5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO-1 defects correlated with cerebral pathology and cognitive deficits. DISCUSSION: We uncovered deficiencies in blood-retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aβ40 deposition suggests a common pathogenic mechanism of failed Aβ clearance via intramural periarterial drainage.

Cerebral amyloid angiopathy (CAA) has been proven to be the most common pathological change in cerebral small vessel disease except arteriosclerosis. In recent years, with the discovery of imaging technology and new imaging markers, the diagnostic rate of CAA has greatly improved. CAA plays an important role in non-hypertensive cerebral hemorrhage and cognitive decline. This review comprehensively describes the etiology, epidemiology, pathophysiological mechanisms, clinical features, imaging manifestations, imaging markers, diagnostic criteria, and treatment of CAA to facilitate its diagnosis and treatment and reduce mortality.

Resumen: Introducción: La inflamación relacionada con la angiopatía amiloide es una entidad caracterizada por una respuesta inflamatoria alrededor de los depósitos de beta amiloide de la microcirculación cerebral. Métodos: Revisión retrospectiva de una serie de pacientes con inflamación relacionada con angiopatía amiloide, que cumplieran criterios clínico-radiológicos o con diagnóstico histopatológico confirmado. Resultados: Se incluyeron siete pacientes, cinco varones, con edad media de 79 años. El inicio fue agudo o subagudo en seis de los casos. La clínica más frecuente fue deterioro cognitivo (n = 6), alteraciones de conducta (n = 5), crisis epilépticas (n = 5), focalidad neurológica (n = 4) y cefalea (n = 2). El líquido cefalorraquídeo fue anormal en tres de cinco casos (pleocitosis linfocitaria e hiperproteinorraquia). Las imágenes de resonancia magnética cerebral más frecuentes consistieron en microhemorragias (n = 7), hiperintensidades subcorticales en secuencia T2-FLAIR (n = 7) y realce leptomeníngeo (n = 6). La afectación fue bilateral en tres de los casos, con predominio en regiones parieto-occipitales (n = 5). Se realizó una tomografía por emisión de positrones (PET) de amiloide en dos pacientes, resultando positiva en uno. Se obtuvo la confirmación histopatológica mediante una biopsia en dos de los casos. Todos los sujetos recibieron tratamiento inmunosupresor, objetivándose una respuesta clínica y radiológica inicial favorable, con recaída radiológica en dos de los casos tras la retirada del tratamiento, y mejorando tras la reinstauración. Conclusiones: El diagnóstico resulta imprescindible de cara a iniciar un tratamiento precoz, ya que ha demostrado mejorar el pronóstico y disminuir las recurrencias. Si bien el diagnóstico definitivo es histopatológico, los criterios clínico-radiológicos permiten el diagnóstico de esta entidad sin necesidad de biopsia. Abstract: Introduction: Cerebral amyloid angiopathy–related inflammation (CAA-ri) is an entity characterised by an inflammatory response to β-amyloid deposition in the walls of cerebral microvessels. Methods: We conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-radiological diagnostic criteria. Results: The study included 7 patients (5 men) with a mean age of 79 years. Disease onset was acute or subacute in 6 patients. The most frequent symptoms were cognitive impairment (n = 6), behavioural alterations (n = 5), epileptic seizures (n = 5), focal neurological signs (n = 4), and headache (n = 2). Cerebrospinal fluid was abnormal in 3 patients (lymphocytic pleocytosis and high protein levels). The most frequent MRI findings were microbleeds (n = 7), subcortical white matter hyperintensities on T2-FLAIR sequences (n = 7), and leptomeningeal enhancement (n = 6). Lesions were bilateral in 3 patients and most frequently involved the parieto-occipital region (n = 5). Amyloid PET studies were performed in 2 patients, one of whom showed pathological findings. Two patients underwent brain biopsy, which confirmed diagnosis. All patients received immunosuppressive therapy. An initially favourable clinical-radiological response was observed in all cases, with 2 patients presenting radiological recurrence after treatment withdrawal, with a subsequent improvement after treatment was resumed. Conclusions: Early diagnosis of CAA-ri is essential: early treatment has been shown to improve prognosis and reduce the risk of recurrence. Although a histopathological study is needed to confirm diagnosis, clinical-radiological criteria enable diagnosis without biopsy.

Background: Cerebellar superficial siderosis (SS) has been recently reported to be present in about 10% of both hereditary and sporadic cerebral amyloid angiopathy (CAA) on 3T MRI using primarily susceptibility-weighted imaging. Objectives: Our aim was to assess cerebellar SS in sporadic CAA patients using 1.5T T2*-weighted MRI and to evaluate possible underlying mechanisms. Method: We retrospectively screened MRI scans of sporadic probable CAA patients initially presenting with intracerebral hemorrhage-, acute subarachnoid hemorrhage- or cortical SS-related symptoms between September 2009 and January 2022 registered in our stroke database. Patients with familial CAA were excluded. On 1.5T T2*-weighted MRI, cerebellar SS (including kappa statistics for interobserver agreement) was assessed together with typical CAA hemorrhagic features and with the presence of supratentorial macrobleed and cortical SS adjacent to the tentorium cerebelli (TC) and TC hemosiderosis. Results: We screened 151 patients and finally included 111 CAA patients (median age 77) with cerebellar SS observed in 6 (5%) patients. Cerebellar SS presence was associated with a higher number of supratentorial macrobleeds (median n = 3 vs. n = 1, p = 0.0012), presence of supratentorial macrobleed adjacent to the TC (p = 0.002), and TC hemosiderosis (p = 0.005). Conclusions: Cerebellar SS in CAA patients can be identified on 1.5T T2*-weighted imaging. Associated MRI characteristics suggest contamination from supratentorial macrobleeds. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Remote intracerebral hemorrhage (RICH) is a rare yet highly consequential complication that can occur after a craniotomy performed for the evacuation of an intracerebral hemorrhage (ICH). In this case report, we present the clinical details of a 74‐year‐old female patient who underwent a supratentorial craniotomy to address an ICH, and subsequently developed RICH. A 74‐year‐old woman was admitted to our department with a severe headache, onset of dysarthria, and left‐sided brachio‐crural hemiparesis. The patient had a history of arterial hypertension and a previous cerebral ischemia incident 2 years prior, potentially due to cerebral amyloid angiopathy. Despite the immediate surgical intervention and intensive care, she succumbed to respiratory distress after developing a contralateral ICH. RICH following craniotomy for an intracerebral hematoma is a rare but potentially devastating complication. Close monitoring, prompt recognition of neurological deterioration, and timely intervention are imperative to optimize patient outcomes. Further research is needed to better understand the underlying mechanisms and risk factors associated with this complication, allowing for improved prevention and management strategies in the future. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status. METHODS: TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology. RESULTS: Severe decreases in retinal vascular zonula occludens‐1 (ZO‐1) and claudin‐5 correlating with abundant arteriolar Aβ40 deposition were identified in MCI and AD patients. Retinal claudin‐5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO‐1 defects correlated with cerebral pathology and cognitive deficits. DISCUSSION: We uncovered deficiencies in blood–retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aβ40 deposition suggests a common pathogenic mechanism of failed Aβ clearance via intramural periarterial drainage. [ABSTRACT FROM AUTHOR]

Key Clinical Message Remote intracerebral hemorrhage (RICH) is a rare yet highly consequential complication that can occur after a craniotomy performed for the evacuation of an intracerebral hemorrhage (ICH). In this case report, we present the clinical details of a 74‐year‐old female patient who underwent a supratentorial craniotomy to address an ICH, and subsequently developed RICH. A 74‐year‐old woman was admitted to our department with a severe headache, onset of dysarthria, and left‐sided brachio‐crural hemiparesis. The patient had a history of arterial hypertension and a previous cerebral ischemia incident 2 years prior, potentially due to cerebral amyloid angiopathy. Despite the immediate surgical intervention and intensive care, she succumbed to respiratory distress after developing a contralateral ICH. RICH following craniotomy for an intracerebral hematoma is a rare but potentially devastating complication. Close monitoring, prompt recognition of neurological deterioration, and timely intervention are imperative to optimize patient outcomes. Further research is needed to better understand the underlying mechanisms and risk factors associated with this complication, allowing for improved prevention and management strategies in the future.

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. [ABSTRACT FROM AUTHOR]

Introduction. In the study of Alzheimer’s disease (AD), the cause-and-effect relationship between neurodegenerative changes and the accompanying amyloid angiopathy is becoming increasingly important. The accumulated clinical data indicates that an important contribution to the pathogenesis of AD is made by neurovascular unit dysfunction, including disruption in permeability of the blood-brain barrier (BBB), microcirculation, and metabolic coupling of cells.Aim. To study the molecular mechanisms of disturbed brain microcirculation and the structural and functional integrity of the BBB in experimental models of AD in vitro under the modulation of CD147 and RAGE.Materials and methods. The study was carried out on C57BL/6 mice. First, we formed an AD model in animals of the experimental group. Then, we isolated and cultured primary cells of the brain, modulated the activity of CD147 and RAGE in endothelial cells using siRNA CD147, siRNA RAGE, cyclophilin A and Aβ1-42, and formed a BBB model in vitro. Further, we assessed transendothelial electrical resistance in the BBB model in vitro, registered the marker molecules of angiogenesis and analyzed the expression of APP in endothelial cells. Statistical processing of the obtained data was carried out using the methods of nonparametric statistics: the Mann – Whitney U test for comparing independent samples and the Wilcoxon test for comparing dependent samples. The level of statistical significance of differences was p ≤ 0.05.Results and discussion. Knockdown of RAGE led to a statistically significant increase in TEER, an intensification of neoangiogenesis, and a decrease in the level of APP expression. At the same time, although CD147 knockdown led to an increase in TEER, it also led to controversial effects on angiogenesis and an increase in APP expression.Conclusion. Analyzing the data obtained, it can be concluded that RAGE and CD147 silencing in the cells of cerebral microvessels can become a promising method for reducing their pathological permeability.

Introduction: Alzheimer disease (AD) and related dementias are characterized by damage caused by neuropathological lesions in the brain. These include AD lesions (plaques and tangles) and non‐AD lesions such as vascular injury or Lewy bodies. We report here an assessment of lesion association to dementia in a large clinic‐based population. Methods: We identified 5272 individuals with neuropathological data from the National Alzheimer's Coordinating Center. Individual lesions, as well as a neuropathological composite score (NPCS) were tested for association with dementia, and both functional and neurocognitive impairment using regression models. Results: Most individuals exhibited mixed pathologies, especially AD lesions in combination with non‐AD lesions. All lesion types were associated with one or more clinical outcomes; most even while controlling for AD pathology. The NPCS was also associated with clinical outcomes. Discussion: These data suggest mixed‐type pathologies are extremely common in a clinic‐based population and may contribute to dementia and cognitive impairment. [ABSTRACT FROM AUTHOR]

Amyloid angiopathy represents 20% of causes of intraparenchymal hematoma. The histopathological examination must carefully look for characteristic vascular abnormalities and the immunohistochemistry for the βA4 peptide must be carried out systematically. In practice, the evacuation products of an intracerebral hematoma must be fully included, because the lesions may be focal. The existence of a neurosurgical history may suggest an iatrogenic etiology when patients are less than 55 years-old., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Evaluating the risk factors for intracerebral hemorrhage is indispensable for primary prevention. However, the pathogenesis varies depending on the bleeding site, and few prospective studies have explored risk factors in detail for each site., Participants and Methods: The Japan Public Health Center-based Prospective Study is a prospective study comprising a population-based sample of Japanese adults in 1990 (Cohort I) and in 1993 (Cohort II). A total of 34,137 participants (11,907 men and 22,230 women) were enrolled in this study and followed up until 2009 for Cohort I and until 2012 for Cohort II. The association between risk factors (age, sex, blood pressure, serum cholesterol, triglycerides, blood glucose, body mass index, smoking, and drinking status) and intracerebral hemorrhage by its bleeding site (lobes, putamen, thalamus, cerebellum, and brainstem) was assessed using Cox proportional hazards analysis., Results: During a median 20-year follow-up, 571 intracerebral hemorrhage events occurred. Hypertension was associated with an increased risk of total intracerebral hemorrhage, but not lobar hemorrhage. The multivariable hazard ratio (95% confidence intervals) was 2.09 (1.75-2.50) for total intracerebral hemorrhage. In contrast, a low serum total cholesterol level was associated only with lobar hemorrhage (1.73 (1.01-2.96)). Heavy drinking was associated with the risk of total and putamen hemorrhage, and obesity was associated with the risk of putamen hemorrhage., Discussion and Conclusion: The present study identified different risk factors depending on the bleeding site of intracerebral hemorrhage., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We postulated that vascular dysfunction mediates the relationship between amyloid load and white matter hyperintensities (WMH) in cerebral amyloid angiopathy (CAA). Thirty-eight cognitively healthy patients with CAA (mean age 70 ± 7.1) were evaluated. WMH was quantified and expressed as percent of total intracranial volume (pWMH) using structural MRI. Mean global cortical Distribution Volume Ratio representing Pittsburgh Compound B (PiB) uptake (PiB-DVR) was calculated from PET scans. Time-to-peak [TTP] of blood oxygen level-dependent response to visual stimulation was used as an fMRI measure of vascular dysfunction. Higher PiB-DVR correlated with prolonged TTP (r = 0.373, p = 0.021) and higher pWMH (r = 0.337, p = 0.039). Prolonged TTP also correlated with higher pWMH (r = 0.485, p = 0.002). In a multivariate linear regression model, TTP remained independently associated with pWMH (p = 0.006) while PiB-DVR did not (p = 0.225). In a bootstrapping model, TTP had a significant indirect effect (ab = 0.97, 95% CI: 0.137–2.461), supporting that the association between PiB-DVR and pWMH is mediated by TTP response. There was no longer a direct effect independent of the hypothesized pathway. Our study suggests that the effect of vascular amyloid load on white matter disease is mediated by vascular dysfunction in CAA. Amyloid lowering strategies might prevent pathophysiological processes leading to vascular dysfunction, therefore limiting ischemic brain injury. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study is to evaluate the magnetic resonance imaging (MRI) findings of central neural system (CNS) superficial siderosis cases and the diagnostic contribution of the susceptibility-weighted imaging (SWI) sequence to conventional imaging. Method. TSE T2-weighted and SWI-MRI of 26 patients diagnosed as CNS-superficial siderosis (CNS-SS) were retrospectively evaluated with 3-Tesla MRI. The localization and type of involvement of SS were reviewed. Results. The CNS-SS were divided into two categories as central amyloid angiopathy-SS (CAA-SS) and non-central amyloid angiopathy-SS (non-CAA-SS). In non-CAA cases, the involvement was typical (classic) in 5 cases and atypical in 9 cases. In 12 of these cases (85.7%), SS findings were observed on both turbo spine echo (TSE) T2 images and SWI imaging, while in 2 cases (14.3%) SS was detected only on SWI images. In 7 of the CAA-SS cases, involvement was focal type SS (58.33%), while 5 cases had diffuse type SS (41.67%) involvement. In the vast majority of cases (n = 10) of this type of SS, involvement was detected only in SWI images, while siderosis was not detected in TSE T2 images. In addition, occult cerebral vascular malformation accompanying SS, which can be observed only in the SWI sequence, was found in a total of 4 cases. In the cross-matching statistical analysis performed between CAA-SS and non-CAA-SS groups and subgroups, SWI was found to be significantly superior to T2 in detecting SS in the CAA-SS group (p:0,007). Conclusions. SWI imaging was superior in detecting SS and detecting cerebral occult vascular malformation in CAA-SS cases. Although the detectability of SS by SWI was high in other groups, no statistically significant difference was found. Under these circumstances, we think that it will be beneficial to add SWI imaging to the routine imaging protocol in cases with suspected CNS-SS.

Abstract Insulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T308 following ex vivo stimulation with insulin (OR = 1.916; estimate = 0.650; p = 0.007) and greater pS616IRS1 immunolabeling in neuronal cytoplasm (OR = 1.610; estimate = 0.476; p = 0.013), were each associated with a higher number of brain infarcts. Secondary analyses showed consistent results for gross infarcts and microinfarcts separately, but no other association including by infarct location (cortical or subcortical). AKT S473 phosphorylation following insulin stimulation was associated with less amyloid angiopathy severity, but not with other vessel pathology including atherosclerosis and arteriolosclerosis. In summary, insulin resistance in the human brain, even among persons without diabetes, is associated with cerebrovascular disease and especially infarcts. The underlying pathophysiologic mechanisms need further elucidation. Because brain infarcts are known to be associated with lower cognitive function and dementia, these data are relevant to better understanding the link between brain metabolism and brain function.

Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits.

Introduction: Hereditary transthyretin (ATTRv) amyloidosis caused by the V30M (p. V50M) mutation is a fatal, neuropathic systemic amyloidosis. Liver transplantation has prolonged the survival of patients and central nervous system (CNS) complications, attributed to amyloid angiopathy caused by CNS synthesis of variant transthyretin, have emerged. The study aimed to ascertain amyloid deposition within the brain in long-term ATTRv amyloidosis survivors with neurological symptoms from the CNS. Methods: A total of 20 patients with ATTR V30M having symptoms from the CNS and a median disease duration of 16 years (8–25 years) were included in this study. The cognitive and peripheral nervous functions were determined for 18 patients cross-sectionally at the time of the investigation. Amyloid brain deposits were examined by [18F]flutemetamol PET/CT. Five patients with Alzheimer's disease (AD) served as positive controls. Result: 60% of the patients with ATTRv had a pathological Z-score in the cerebellum, compared to only 20% in the patients with AD. 75% of the patients with transient focal neurological episodes (TFNEs) displayed a pathological uptake only in the cerebellum. Increased cerebellar uptake was related to an early age of onset of the ATTRv disease. 55% of the patients with ATTRv had a pathological Z-score in the global cerebral region compared to 100% of the patients with AD. Conclusion: Amyloid deposition within the brain after long-standing ATTRv amyloidosis is common, especially in the cerebellum. A cerebellar amyloid uptake profile seems to be related to TFNE symptoms. [ABSTRACT FROM AUTHOR]

We report the case of long-term follow-up of brain magnetic imaging of cerebral amyloid angiopathy. Cerebral amyloid angiopathy is often considered a major cause of spontaneous intracerebral hemorrhage in the elderly. This case illustrates the markedly progressive clinical and radiological features of the vasculopathic process in 10 years.

IntroductionHereditary transthyretin (ATTRv) amyloidosis caused by the V30M (p. V50M) mutation is a fatal, neuropathic systemic amyloidosis. Liver transplantation has prolonged the survival of patients and central nervous system (CNS) complications, attributed to amyloid angiopathy caused by CNS synthesis of variant transthyretin, have emerged. The study aimed to ascertain amyloid deposition within the brain in long-term ATTRv amyloidosis survivors with neurological symptoms from the CNS.MethodsA total of 20 patients with ATTR V30M having symptoms from the CNS and a median disease duration of 16 years (8–25 years) were included in this study. The cognitive and peripheral nervous functions were determined for 18 patients cross-sectionally at the time of the investigation. Amyloid brain deposits were examined by [18F]flutemetamol PET/CT. Five patients with Alzheimer's disease (AD) served as positive controls.Result60% of the patients with ATTRv had a pathological Z-score in the cerebellum, compared to only 20% in the patients with AD. 75% of the patients with transient focal neurological episodes (TFNEs) displayed a pathological uptake only in the cerebellum. Increased cerebellar uptake was related to an early age of onset of the ATTRv disease. 55% of the patients with ATTRv had a pathological Z-score in the global cerebral region compared to 100% of the patients with AD.ConclusionAmyloid deposition within the brain after long-standing ATTRv amyloidosis is common, especially in the cerebellum. A cerebellar amyloid uptake profile seems to be related to TFNE symptoms.

Cerebrovascular lesions are prevalent in late life and frequently co-occur but the relationship to cognitive impairment is complicated by the lack of consensus around which lesions represent hallmark pathologies for vascular impairment, particularly in the presence of Alzheimer’s disease (AD). We developed an easily applicable model of cerebrovascular disease (CVD), defined as the presence of two or more lesions: moderate to severe cerebral amyloid angiopathy, moderate to severe arteriolosclerosis, infarcts (large, lacunar, or micro), and/or hemorrhages. AD was defined as intermediate or high AD neuropathologic change. The contribution of vascular risk factors such as atherosclerosis and/or a health history of heart disease, hyperlipidemia, stroke events, diabetes, or hypertension was also assessed. Logistic regression analysis reported the association of CVD with increasing age, vascular risk factors, AD, and cognitive impairment in this study of 1,485 autopsied individuals. Cerebrovascular lesions were present in 48% and 16% had CVD. Increasing age associated with all lesions (p0.61). From this, we conclude that a simple, additive model of CVD is 1) age and AD-associated, 2) is associated with vascular risk factors, and 3) clinically correlates with cognitive decline independent of AD.

CAA-ri is a reversible and rare encephalopathy that may manifest in patients with CAA. In this short article, we describe CT and MRI findings of CAA-ri in a 67-year-old man presented to emergency with sudden aphasia and acute cognitive dysfunction, underlining the pivotal role of neuroimaging in the diagnostic path. [ABSTRACT FROM AUTHOR]

Amyloidosis caused by systemic deposition of transthyretin (TTR) is called ATTR amyloidosis and mainly includes hereditary ATTR (ATTRv) amyloidosis and wild-type ATTR (ATTRwt) amyloidosis. Until recently, ATTRv amyloidosis had been considered a disease in the field of neurology because neuropathic symptoms predominated in patients described in early reports, whereas advances in diagnostic techniques and increased recognition of this disease revealed the presence of patients with cardiomyopathy as a predominant feature. In contrast, ATTRwt amyloidosis has been considered a disease in the field of cardiology. However, recent studies have suggested that some of the patients with ATTRwt amyloidosis present tenosynovial tissue complications, particularly carpal tunnel syndrome, as an initial manifestation of amyloidosis, necessitating an awareness of this disease among neurologists and orthopedists. Although histopathological confirmation of amyloid deposits has traditionally been considered mandatory for the diagnosis of ATTR amyloidosis, the development of noninvasive imaging techniques in the field of cardiology, such as echocardiography, magnetic resonance imaging, and nuclear imaging, enabled nonbiopsy diagnosis of this disease. The mechanisms underlying characteristic cardiac imaging findings have been deciphered by histopathological studies. Novel disease-modifying therapies for ATTR amyloidosis, such as TTR stabilizers, short interfering RNA, and antisense oligonucleotides, were initially approved for ATTRv amyloidosis patients with polyneuropathy. However, the indications for the use of these disease-modifying therapies gradually widened to include ATTRv and ATTRwt amyloidosis patients with cardiomyopathy. Since the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, occurred, the minimization of hospital visits and telemedicine have become increasingly important. As older age and cardiovascular disease are major factors associated with increased disease severity and mortality of COVID-19, many ATTR amyloidosis patients are at increased risk of disease aggravation when they are infected with SARS-CoV-2. From this viewpoint, close interspecialty communication to determine the optimal interval of evaluation is needed for the management of patients with ATTR amyloidosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden. Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia. Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C1 scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C2 scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia. Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an acknowledged syndrome of reversible encephalopathy, also known as cerebral b-related angiitis. It is characterized by brisk progressive higher mental dysfunctions, headaches, seizures/epilepsy, and behavioral changes, and is highly responsive to immunosuppressive medications. To quickly and properly determine patients' management plans and prognoses, doctors are left with only CAA-ri-associated behavioral changes and seizures, in addition to a high index of suspicion of the correct diagnosis. Case Report: A 67-year-old woman was presented to the emergency room (ER) with behavioral changes and seizures. Upon screening, the patient was found to have radiological evidence of asymmetrical cortical-subcortical white-matter lesions accompanied by multiple cerebral microbleeds in the background of the negative screening for infectious/neoplastic and paraneoplastic processes. After undergoing a brain biopsy, the diagnosis was confirmed to be amyloid deposition within the inflammatory vessel walls. The patient showed a dramatic improvement after methylprednisolone pulse therapy, plasma exchange, and rituximab maintenance. Conclusions: We encourage and support brain biopsies to confirm highly suspicious CAA-ri atypical cases to initiate early treatment and achieve the best outcome without any further delays. [ABSTRACT FROM AUTHOR]

Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden.Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia.Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C1 scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C2 scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia.Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load.

Objective. The aim of this study is to evaluate the magnetic resonance imaging (MRI) findings of central neural system (CNS) superficial siderosis cases and the diagnostic contribution of the susceptibility-weighted imaging (SWI) sequence to conventional imaging. Method. TSE T2-weighted and SWI-MRI of 26 patients diagnosed as CNS-superficial siderosis (CNS-SS) were retrospectively evaluated with 3-Tesla MRI. The localization and type of involvement of SS were reviewed. Results. The CNS-SS were divided into two categories as central amyloid angiopathy-SS (CAA-SS) and non-central amyloid angiopathy-SS (non-CAA-SS). In non-CAA cases, the involvement was typical (classic) in 5 cases and atypical in 9 cases. In 12 of these cases (85.7%), SS findings were observed on both turbo spine echo (TSE) T2 images and SWI imaging, while in 2 cases (14.3%) SS was detected only on SWI images. In 7 of the CAA-SS cases, involvement was focal type SS (58.33%), while 5 cases had diffuse type SS (41.67%) involvement. In the vast majority of cases (n = 10) of this type of SS, involvement was detected only in SWI images, while siderosis was not detected in TSE T2 images. In addition, occult cerebral vascular malformation accompanying SS, which can be observed only in the SWI sequence, was found in a total of 4 cases. In the cross-matching statistical analysis performed between CAA-SS and non-CAA-SS groups and subgroups, SWI was found to be significantly superior to T2 in detecting SS in the CAA-SS group (p:0,007). Conclusions. SWI imaging was superior in detecting SS and detecting cerebral occult vascular malformation in CAA-SS cases. Although the detectability of SS by SWI was high in other groups, no statistically significant difference was found. Under these circumstances, we think that it will be beneficial to add SWI imaging to the routine imaging protocol in cases with suspected CNS-SS. [ABSTRACT FROM AUTHOR]

Spontaneous cerebellar hemorrhage (CH) is a critical neurosurgical event. It is usually categorized as a homogenous group under the general term of deep/nonlobar intracerebral hemorrhage. However, increasing evidence suggests it is composed of 2 subgroups, separated from each other by their anatomic location (deep vs. superficial), as well as by their vascular etiology (small vessel disease vs. cerebral amyloid angiopathy). To identify any clinically significant differences between anatomically separated subgroups of CHs: deep versus superficial. This is a retrospective study on patients who were diagnosed with spontaneous CHs at a single tertiary center. On the basis of the radiologic location of the hematoma, patients were divided into 2 groups: deep (group 1) and superficial (group 2). Computerized medical records were extracted for multiple variables. A total of 69 patients fulfilled the inclusion criteria. Fifty-three (77%) were in group 1, and 16 (23%) were in group 2. Having any vascular risk factor was associated with the highest odds ratio for having a deep CH. Morbid obesity (body mass index ≥30) and the use of antiplatelets were also associated with increased odds ratios. Group 1 is also associated with high prevalence of intraventricular hemorrhage, acute hydrocephalus, and less favorable outcome. This study supports the notion that CH is most likely a heterogenous condition, composed of 2 subgroups, separated from each other in terms of anatomic location, vascular etiologies, and clinical consequences. Further studies on large cohort of patients are needed in order to accurately define the subgroups of this life-threatening event. [ABSTRACT FROM AUTHOR]

Insulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T308 following ex vivo stimulation with insulin (OR = 1.916; estimate = 0.650; p = 0.007) and greater pS616IRS1 immunolabeling in neuronal cytoplasm (OR = 1.610; estimate = 0.476; p = 0.013), were each associated with a higher number of brain infarcts. Secondary analyses showed consistent results for gross infarcts and microinfarcts separately, but no other association including by infarct location (cortical or subcortical). AKT S473 phosphorylation following insulin stimulation was associated with less amyloid angiopathy severity, but not with other vessel pathology including atherosclerosis and arteriolosclerosis. In summary, insulin resistance in the human brain, even among persons without diabetes, is associated with cerebrovascular disease and especially infarcts. The underlying pathophysiologic mechanisms need further elucidation. Because brain infarcts are known to be associated with lower cognitive function and dementia, these data are relevant to better understanding the link between brain metabolism and brain function. [ABSTRACT FROM AUTHOR]

Retinal angiopathy is a known ocular manifestation of hereditary transthyretin amyloidosis (ATTRv). Optical coherence tomography angiography (OCT-A) is a recent noninvasive imaging technique, used in other retinal vascular diseases. Our purpose was to analyse subclinical changes in retinal vessels, with OCT-A, in patients with ATTRv amyloidosis. Observational cross-sectional study in Centro Hospitalar e Universitário do Porto in the cohort of patients with genetic diagnosis of ATTRv. Patients were included if they had just one eye with scalloped iris (the other eye without scalloped iris), postulating eyes were at different stages, in the same patient. Patients were excluded if they had other manifestations of ocular ATTRv amyloidosis, namely clinical retinal angiopathy and/or vitreous opacities. The group of eyes with scalloped iris were compared with eyes without scalloped iris, using paired tests. Values are shown as Δ = mean difference between groups; p = p-value, d = Cohen's d for effect size measurement. Twenty-four patients (24 eyes in each group) were included. Mean age was 46.5 ± 5.0 years. Eyes with scalloped iris showed attenuated retinal vascular network: larger foveal avascular zone (FAZ) area (Δ = +0.02 mm2, p = 0.002, d = 0.70); decreased foveal vascular density (Δ = –3.57%, p = 0.001, d = –0.75); superficial (Δ = –1.50%, p = 0.049, d = –0.43) and deep (Δ = –2.53%, p = 0.023, d = –0.50) plexus vascular density. Acircularity index was superior in scalloped iris eyes (Δ = 0.04, p = 0.004, d = –0.65), representing an abnormal FAZ morphology. Scalloped iris in ATTRv eyes are associated with a more advanced subclinical retinal angiopathy, than eyes without scalloped iris. Our results identify for the first time and in vivo, early changes in retinal vessels in ATTRv amyloidosis. Henceforward, OCT-A may play a role in the evaluation of ATTRv patients oculopathy and the effectiveness of future eye targeting treatments. [ABSTRACT FROM AUTHOR]

Transthyretin (TTR) tetramer dissociation is rate limiting for aggregation and subunit exchange. Slowing of TTR tetramer dissociation via kinetic stabiliser binding slows cardiomyopathy progression. Quadruplicate subunit exchange comparisons of the drug candidate AG10, and the drugs tolcapone, diflunisal, and tafamidis were carried out at 1, 5, 10, 20 and 30 µM concentrations in 4 distinct pooled wild type TTR (TTRwt) human plasma samples. These experiments reveal that the concentration dependence of the efficacy of each compound at inhibiting TTR dissociation was primarily determined by the ratio between the stabiliser's dissociation constants from TTR and albumin, which competes with TTR to bind kinetic stabilisers. The best stabilisers, tafamidis (80 mg QD), AG10 (800 mg BID), and tolcapone (3 x 100 mg over 12 h), exhibit very similar kinetic stabilisation at the plasma concentrations resulting from these doses. At a 10 µM plasma concentration, AG10 is slightly more potent as a kinetic stabiliser vs. tolcapone and tafamidis (which are similar), which are substantially more potent than diflunisal. Dissociation of TTR can be limited to 10% of its normal rate at concentrations of 5.7 µM AG10, 10.3 µM tolcapone, 12.0 µM tafamidis, and 188 µM diflunisal. The potency similarities revealed by our study suggest that differences in safety, adsorption and metabolism, pharmacokinetics, and tissue distribution become important for kinetic stabiliser clinical use decisions. [ABSTRACT FROM AUTHOR]

Non-convulsive SE (NCSE) is characterized by altered consciousness with or without slight motor manifestations or other phenomena such as aphasia, sensory, auditory, emotional, gustatory or other symptoms.A 69-year-old right-handed man developed the sudden onset of apraxia in his right arm. On admission, the patient was alert and well oriented. In his past medical history, an intracerebral hematoma (ICH) in the left temporo-parietal area was noted occurred five years before the current admission.An electroencephalography (EEG) showed rhythmic theta–delta activity with fluctuating frequency between 1.5 and 5 Hz in the left centro-parieto-temporal area, which promptly responded to the intravenous injection of 2 mg clonazepam and 1000 mg levetiracetam. Apraxia resolved completely and the EEG demonstrated intermittent non-rhythmic delta–theta slowing in the left temporo-parietal area. A cranial CT scan showed residual cystic encephalomalacia in the left temporo-parietal area due to the previous ICH. An MRI exhibited an old parenchymal defect in the left temporo-parietal area with a residual hemosiderin rim on the susceptibility weighted imaging (SWI) and no diffusion restriction on the diffusion weighted image (DWI).NCSE presented with right arm apraxia in our patient with a post-hemorrhagic residual parenchymal defect in the left temporo-parietal area.

We report the case of long-term follow-up of brain magnetic imaging of cerebral amyloid angiopathy. Cerebral amyloid angiopathy is often considered a major cause of spontaneous intracerebral hemorrhage in the elderly. This case illustrates the markedly progressive clinical and radiological features of the vasculopathic process in 10 years. [ABSTRACT FROM AUTHOR]

Objective: Spontaneous brain microhemorrhages in elderly people are present to some degree in Alzheimer’s disease patients but have been linked to brain atrophy in the absence of obvious cognitive decline. Brain microhemorrhages have recently been described in older dogs, but it is unclear whether these are associated with brain atrophy. Diminution of interthalamic adhesion size-as measured on MRI or CT-has been shown to be a reliable indicator of brain atrophy in dogs with canine cognitive dysfunction (CCD) in comparison with successfully aging dogs. We hypothesized that aging dogs with brain microhemorrhages presenting for neurologic dysfunction but without obvious features of cognitive decline would have small interthalamic adhesion measurements, like dogs with CCD, compared with control dogs. The objective of this study was to compare interthalamic adhesion size between three groups of aging (>9 years) dogs: (1) neurologically impaired dogs with presumptive spontaneous brain microhemorrhages and no clinical evidence of cognitive dysfunction (2) dogs with CCD (3) dogs without clinical evidence of encephalopathy on neurologic examination (control dogs). MR images from 52 aging dogs were reviewed and measurements were obtained of interthalamic adhesion height (thickness) and mid-sagittal interthalamic adhesion area for all dogs, in addition to total brain volume. Interthalamic adhesion measurements, either absolute or normalized to total brain volume were compared between groups. Signalment (age, breed, sex), body weight, presence and number of SBMs, as well as other abnormal MRI findings were recorded for all dogs. Results: All interthalamic adhesion measurement parameters were significantly (P < 0.05) different between control dogs and affected dogs. Both dogs with cognitive dysfunction (12/15; 80%) and dogs with isolated brain microhemorrhages had more microhemorrhages than control dogs (3/25; 12%). Affected dogs without cognitive dysfunction had significantly more microhemorrhages than dogs with cognitive dysfunction. In addition to signs of cognitive impairment for the CCD group, main clinical complaints for SBM and CCD dogs were referable to central vestibular dysfunction, recent-onset seizure activity, or both. Geriatric dogs with spontaneous brain microhemorrhages without cognitive dysfunction have similar MRI abnormalities as dogs with cognitive dysfunction but may represent a distinct disease category. [ABSTRACT FROM AUTHOR]

• In patients with ICH and AF, early LAAO can be safely performed within 30 days of ICH. • Despite low-intensity antithrombotic regimens, the risk of recurrent ICH remains high and could be attributed to cerebral amyloid angiopathy. • The burden and location of microbleeds in MR could improve risk stratification for ICH recurrence. Patients with atrial fibrillation (AF) and intracerebral hemorrhage (ICH) are at high risk of ischemic and recurrent bleeding events. Therefore, the decision of restarting or avoiding anticoagulation is challenging. Left atrial appendage occlusion (LAAO) is an alternative for these patients. However, few data are available about safety of early LAAO and factors associated with ischemic stroke and ICH recurrence. A unicentric, observational, retrospective study including all patients with AF and a previous ICH who underwent LAAO. We analyzed baseline clinical and neuroimaging characteristics, procedural outcomes, post-procedural therapies and long-term follow-up. Forty patients were included, whose mean age was 76.6 ±7.6 years and 73 % were men. In patients in whom a Magnetic Resonance (MR) was performed (n=22, 55 %), cortical microbleeds were detected in 15 (68 %) and cortical superficial siderosis in one patient. The procedure was successful and safe in 100 % of the patients and it was performed within 30 days of the ICH in 37 % of them. After a median follow up of 46.2 months [26-69], intracranial hemorrhage (ICrH) recurrence occurred in 6 patients (5 ICH and 1 subdural hematoma –SDH-) and the index ICH was lobar in all of them. Ischemic events were significantly lower than expected according to the CHA2DS2-VASc score (7.5 % vs. 16.6 %, p=0.048) and bleeding events were similar to expected by the HAS-BLED score (20 % vs 23.4 %, p=0.63). In patients with ICH and AF, early LAAO was found to be safe and associated with a reduction in ischemic stroke. However, recurrent ICH risk remains high, and it appears to be mainly driven by cerebral amyloid angiopathy. [ABSTRACT FROM AUTHOR]

Background In patients with mechanical heart valves, cerebral susceptibility‐weighted imaging (SWI) lesions on magnetic resonance imaging, postulated to be caused by degenerative metallic abrasion, are frequently referred to as valve abrasion. It remains unclear whether valve implantation not requiring cardiopulmonary bypass or biological heart valves also shows those lesions. Methods and Results Two blinded readers rated SWI lesions and cerebral amyloid angiopathy probability according to established criteria on brain magnetic resonance imaging pre‐ and postinterventionally. We assessed the association between valve type/cardiopulmonary bypass use and SWI lesion count on the first postinterventional scan using multivariable logistic regression. On postinterventional magnetic resonance imaging, 57/58 (98%) patients with mechanical heart valves had at least 1 and 46/58 (79%) 3 or more SWI lesions, while 92/97 (95%) patients with biological heart valves had at least 1 and 72/97 (74%) 3 or more SWI lesions. On multivariate analysis, duration of cardiopulmonary bypass during implantation significantly increased the odds of having SWI lesions on the first postinterventional magnetic resonance imaging (β per 10 minutes 0.498; 95% CI, 0.116–0.880; P=0.011), whereas valve type showed no significant association (P=0.338). Thirty‐seven of 155 (23.9%) patients fulfilled the criteria of possible/probable cerebral amyloid angiopathy. Conclusions SWI lesions in patients with artificial heart valves evolve around the time point of valve implantation and the majority of patients had multiple lesions. The missing association with the valve type weakens the hypothesis of degenerative metallic abrasion and highlights cardiopulmonary bypass as the main risk factor for SWI occurrence. SWI lesions associated with cardiac procedures can mimic cerebral amyloid angiopathy. Further research needs to clarify whether those lesions are associated with intracranial hemorrhage after intravenous thrombolysis or anticoagulation.

Cerebral amyloid angiopathy (CAA) has been proven to be the most common pathological change in cerebral small vessel disease except arteriosclerosis. In recent years, with the discovery of imaging technology and new imaging markers, the diagnostic rate of CAA has greatly improved. CAA plays an important role in non-hypertensive cerebral hemorrhage and cognitive decline. This review comprehensively describes the etiology, epidemiology, pathophysiological mechanisms, clinical features, imaging manifestations, imaging markers, diagnostic criteria, and treatment of CAA to facilitate its diagnosis and treatment and reduce mortality.

Background: Although cerebral microbleeds (CMBs) are commonly observed in patients with Alzheimer's disease (AD), their clinical relevance for AD remains unclear.Objective: We investigated the significance of CMBs in AD by examining the relationship between CMBs and cerebral blood flow (CBF) in patients with AD.Methods: Thirty-four patients (aged 77.9±7.6 years; 17 men) with probable AD and multiple (≥8) CMBs were selected from 394 consecutive patients. For each lobe of the brain, the correlation between the number of CMBs observed on susceptibility-weighted images and the decrease in CBF observed on single-photon emission computed tomography was assessed.Results: The number of microbleeds was significantly correlated with the severity of decrease in the occipital lobe (Spearman's r = 0.531, p < 0.001) and temporal lobe (r = 0.437, p < 0.001) but not in the frontal lobe (r = 0.201, p = 0.101) and parietal lobe (r = 0.178, p = 0.146). These results were unchanged in the partial correlational analysis after controlling the effect of other small vessel disease such as lacunars and white matter hyperintensities.Conclusion: Multiple CMBs are associated with cerebral hypoperfusion in AD. The effects of CMBs on CBF differed according to brain location, possibly reflecting different distributions of the underlying cerebral amyloid angiopathy and AD-related histopathology, such as neurofibrillary tangles. [ABSTRACT FROM AUTHOR]

Abstract Introduction The novel D678H amyloid precursor protein (APP) gene mutation has been called the "Taiwan mutation". The study aims to identify amyloid deposition patterns and clinical features associated with this mutation. Methods we analyzed the clinical manifestations, brain neuroimages and 18F-AV-45 positron emission tomography (PET) findings in symptomatic patients and asymptomatic subjects with the autosomal-dominant Alzheimer's disease (AD). We compared the amyloid deposition pattern among 10 patients with genetically-positive familial cognitive decline (CD), 18 patients with sporadic CD, and 19 healthy controls. Results The clinical features were the early onset of memory impairment in all 10 patients and cerebral amyloid angiopathy in 3 patients. The characteristic results of brain 18F-AV-45 PET included the highest standard uptake value ratio (SUVR) in the occipital and cerebellar cortical areas in the genetically-positive CD patients. In subgroup analysis, the familial AD patients had a decreased amyloid SUVR trend in most areas except for cerebellar cortex compared to those with familial mild cognitive impairment. Conclusion Our data indicate that the familial D678H gene mutation have resulted in a more potent amyloid burden than in the patients with sporadic AD patients. The high amyloid uptake in the occipital area is characteristic of the specific Taiwan APP gene. Highlights • The study evaluated the amyloid patterns and clinical features in the Taiwan familial AD with D678H APP mutation. • Early onset of memory impairment and cerebral amyloid angiopathy in 2 patients. • The highest stardand uptake value ratio in the occipital and cerebellar cortical areas in the gCD patients. • The familial D678H gene mutation patients have a more potent amyloid burden than the sporadic AD patients [ABSTRACT FROM AUTHOR]