Imaging Markers of Subcortical Vascular Dementia in Patients With Multiple-Lobar Cerebral Microbleeds

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.

COVID-19 Lockdown Effect on Not Institutionalized Patients with Dementia and Caregivers

SARS-COV-2 is a severe medical condition. Old patients are very vulnerable, but they have been studied only as institutionalized patients. During the lock-down, little attention is dedicated to old, demented patients who lived at home. This study wants to examine their behavioral reactions by video-phone follow-up. We conducted a longitudinal study in subcortical vascular dementia (sVAD) patients. We enrolled 221 sVAD, not institutionalized patients. We divided sVAD patients into low-medium grade sVAD (A) and severe sVAD (B), based on neuroimaging severity degree and executive alterations. At baseline, at the end of lock-down, and two months later, global behavioral symptoms were recorded for each patient. We found significantly higher scores of general behavioral deterioration, anxiety, delusions, hallucinations and apathy after controlling for sVAD severity. The direct consequence was a drastic increment of psychotropic drugs prescribed and employed during the lock-down. Moreover, caregivers’ stress has been evaluated, together with their anxiety and depression levels. During the lock-down, their scores increased and reflected a severe worsening of their behavior. Our data demonstrate that social isolation induces a severe perception of loneliness and abandonment; these fears can exacerbate behavior disturbances in old-aged frail persons. Thus, these can be considered as indirect victims of SARS-COV-2.

Association of the Irregular 3-Dimensional Shape of White Matter Hyperintensities with Cognitive Function

<b><i>Introduction:</i></b> The irregular shapes of white matter hyperintensities (WMHs) are associated with poor cognitive function, diabetes, or lacunes. However, the association between the WMH shape and dementia remains understudied. We investigated the association between the calculated shape index of WMH and the diagnosis of dementia and cognitive function. <b><i>Methods:</i></b> The inverse sphericity index (ISI_WMH) and volume of WMHs (VOL_WMH) were compared among 82 participants with normal cognition, 82 with Alzheimer’s dementia (AD), and 82 with subcortical vascular dementia (SVD). We examined the associations of ISI_WMH and VOL_WMH with the modified Hachinski Ischemic Score (mHIS), diagnosis of AD and SVD, and cognitive test scores, using linear, multinomial, or hierarchical linear regression models. <b><i>Results:</i></b> The mHIS was associated with both ISI_WMH (β = 0.326, <i>p</i> &#x3c; 0.001) and VOL_WMH (β = 0.299, <i>p</i> &#x3c; 0.001). Both ISI_WMH and VOL_WMH were associated with the SVD diagnosis (odds ratio [OR] = 2.685, <i>p</i> = 0.002, ISI_WMH; OR = 2.597, <i>p</i> = 0.005, VOL_WMH), but not with AD. The SVD diagnosis was better explained when the multinomial regression model included both ISI_WMH and VOL_WMH instead of VOL_WMH alone (χ² = 20.768, df = 2, <i>p</i> &#x3c; 0.001). The Trail Making Test-D (TMT-D) scores of the SVD patients were associated with both ISI_WMH (β = 0.308) and VOL_WMH (β = 0.293). <b><i>Conclusion:</i></b> An irregular WMH shape may be associated with the high cerebrovascular component of cognitive impairment and the diagnosis and low cognitive flexibility of SVD, which may improve the prediction of SVD diagnosis when used in combination with WMH volume.

Case Report on a Misdiagnosed Case of Subcortical Vascular Dementia – the Importance of Sound Knowledge of Psychiatry With Proper History Taking

Psychiatric symptoms at presentation may often be missed, if not suspected or specifically explored. A missed psychiatric diagnosis may lead to dire consequences in terms of poor quality of life and function for the patient, affecting overall quality of healthcare provided. This lady presented with depressive symptoms after multiple strokes and was initially diagnosed as post stroke depression. However, after it was observed that she did not show any improvement in symptoms despite being on antidepressants, subsequent further investigations revealed a history more suggestive of subcortical vascular dementia. Consequently, detailed neuropsychological and neuropsychiatric assessments, including NUCOG, and relevant investigations including MRI brain scans were performed suggesting a diagnosis of vascular dementia. This case illustrates that an insufficiently thorough assessment and treatment process results in unnecessary morbidity, prolongs duration of illness, and increases social and occupational dysfunction to the patient. Hence, it further underscores the need to perform a thorough history, physical examination and relevant investigations to ensure organic etiologies are ruled out in clients with relevant sociodemographic and clinical risk factors.

An Iatrogenic Model of Brain Small-Vessel Disease: Post-Radiation Encephalopathy

We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia (sVAD). Patients with any form of primitive cerebral neoplasia underwent whole-brain radiotherapy. All the tumor patients had regional field partial brain RT, which encompassed each tumor, with an average margin of 2.6 cm from the initial target tumor volume. We observed in our patients who have been exposed to a higher dose of RT (30–65 Gy) a cognitive and behavior decline similar to that observed in sVAD, with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect. Multiple mechanisms are likely to be involved in radiation-induced cognitive impairment. The active site of RT brain damage is the white matter areas, particularly the internal capsule, basal ganglia, caudate, hippocampus, and subventricular zone. In all cases, radiation damage inside the brain mainly focuses on the cortical–subcortical frontal loops, which integrate and process the flow of information from the cortical areas, where executive functions are “elaborated” and prepared, towards the thalamus, subthalamus, and cerebellum, where they are continuously refined and executed. The active mechanisms that RT drives are similar to those observed in cerebral small vessel disease (SVD), leading to sVAD. The RT’s primary targets, outside the tumor mass, are the blood–brain barrier (BBB), the small vessels, and putative mechanisms that can be taken into account are oxidative stress and neuro-inflammation, strongly associated with the alteration of NMDA receptor subunit composition.

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

Proper regulation and patency of cerebral microcirculation is crucial for maintaining a healthy brain. Capillary stalling, i.e., the brief interruption of microcirculation mainly by leukocytes, has been observed in several diseases and contributes to disease pathogenesis or progression. However, the underpinning mechanism for leukocyte capillary plugging remains elusive. Therefore, we investigated the mechanism of capillary stalling in mice during the development of subcortical vascular dementia (SVaD), the most common type of vascular dementia characterized by impaired microcirculation and associated pathological features. Longitudinal optical coherence tomography angiography showed increased number of stalled segments as the disease progressed, while two-photon microscopy indicated a less extensive endothelial glycocalyx (EG) in the stalled segments. We also found that increased gliosis and blood-brain barrier leakage were correlated with the increased number of stalled segments. Based on the above, we conclude that EG potentially mediates capillary stalling and can be a therapeutic target of SVaD.