Gargi Banerjee

Novel imaging techniques in cerebral small vessel diseases and vascular cognitive impairment

Dementia is a global growing concern, affecting over 35 million people with a global economic impact of over

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

604 billion US. With an ageing population the number of people affected is expected double over the next two decades. Vascular cognitive impairment can be caused by various types of cerebrovascular disease, including cortical and subcortical infarcts, and the more diffuse white matter injury due to cerebral small vessel disease. Although this type of cognitive impairment is usually considered the second most common form of dementia after Alzheimers disease, there is increasing recognition of the vascular contribution to neurodegeneration, with both pathologies frequently coexisting. The aim of this review is to highlight the recent advances in the understanding of vascular cognitive impairment, with a focus on small vessel diseases of the brain. We discuss recently identified small vessel imaging markers that have been associated with cognitive impairment, namely cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and microinfarcts. We will also consider quantitative techniques including diffusion tensor imaging, magnetic resonance perfusion imaging with arterial spin labelling, functional magnetic resonance imaging and positron emission tomography. As well as potentially shedding light on the mechanism by which cerebral small vessel diseases cause dementia, these novel imaging biomarkers are also of increasing relevance given their ability to guide diagnosis and reflect disease progression, which may in the future be useful for therapeutic interventions. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

Cognitive Impairment Before Intracerebral Hemorrhage Is Associated With Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) has never been more relevant. The last 5 years have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer’s disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer’s and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings. This review aims to provide a 5-year update on these recent advances, as well as a look towards future directions for CAA research and clinical practice.

Response by Banerjee et al to Letter Regarding Article, “Cognitive Impairment Before Intracerebral Hemorrhage Is Associated With Cerebral Amyloid Angiopathy”

Background and Purpose— Although the association between cerebral amyloid angiopathy (CAA) and cognitive impairment is increasingly recognized, it is not clear whether this is because of the impact of recurrent intracerebral hemorrhage (ICH) events, disruptions caused by cerebral small vessel damage, or both. We investigated this by considering whether cognitive impairment before ICH was associated with neuroimaging features of CAA on magnetic resonance imaging. Methods— We studied 166 patients with neuroimaging-confirmed ICH recruited to a prospective multicentre observational study. Preexisting cognitive impairment was determined using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Magnetic resonance imaging markers of cerebral small vessel disease, including CAA, were rated by trained observers according to consensus guidelines. Results— The prevalence of cognitive impairment before ICH was 24.7% (n=41) and, in adjusted analyses, was associated with fulfilling the modified Boston criteria for probable CAA at presentation (odds ratio, 4.01; 95% confidence interval, 1.53–10.51; P=0.005) and a higher composite CAA score (for each point increase, odds ratio, 1.42; 95% confidence interval, 1.03–1.97; P=0.033). We also found independent associations between pre-ICH cognitive decline and the presence of cortical superficial siderosis, strictly lobar microbleeds, and lobar ICH location, but not with other neuroimaging markers, or a composite small vessel disease score. Conclusions— CAA (defined using magnetic resonance imaging markers) is associated with cognitive decline before symptomatic ICH. This provides evidence that small vessel disruption in CAA makes an independent contribution to cognitive impairment, in addition to effects due to brain injury caused directly by ICH. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316.

Domain-specific characterisation of early cognitive impairment following spontaneous intracerebral haemorrhage

We thank Cao et al for their interest in our work on the associations of preexisting cognitive impairment in patients with intracerebral hemorrhage.1 We agree that the association between preexisting cognitive impairment and cortical superficial siderosis (cSS) suggests that cSS might directly cause cortical injury or dysfunction through specific toxic effects of iron species or hemosiderin deposition. However, we think that the magnitude and direction of the associations between strictly lobar microbleeds (odds ratio, 2.47; 95% confidence interval, 0.95–6.37) and lobar intracerebral hemorrhage (odds ratio, 2.29; 95% confidence interval, 0.99–5.31) are also likely to be important for cognitive function although they did not reach statistical significance because of our relatively small sample …

Erratum to: Convexity subarachnoid haemorrhage has a high risk of intracerebral haemorrhage in suspected cerebral amyloid angiopathy

Cognitive deficits after spontaneous intracerebral haemorrhage (ICH) are common and result in functional impairment, but few studies have examined deficits across cognitive domains in the subacute phase. This study aims to describe the cognitive profile following acute ICH and explore how cerebral amyloid angiopathy (CAA) may impact performance. We retrospectively reviewed 187 consecutive patients with ICH (mean age 58.9 years, 55.6% male) with available imaging and neuropsychological data (median 12 days after stroke). In our cohort, 84% (n = 158) were impaired in at least one cognitive domain and 65% (n = 122) in two or more domains. Deficits in non-verbal IQ (76.6%), information processing speed (62.4%) and executive functions (58.1%) were most common. Patients with lobar ICH (n = 92) had more deficits in naming and visual perception than those with non-lobar ICH, but not in adjusted analyses. Patients with probable CAA (n = 21) had more deficits in verbal IQ, visual perception and executive functions than those without probable CAA; in adjusted analyses, probable CAA predicted impairment in verbal IQ (OR 38.6, 95% CI 3.2 to 465.4, p = 0.004) and executive function (OR 3.4, 95% CI 1.0 to 11.7, p = 0.050). We conclude that cognitive deficits following ICH are common across domains, and that those with CAA appear to have a different cognitive profile. Replication of this work in larger cohorts will be important for confirming and further quantifying these observations.