Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review.

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-ß protein deposition which is associated with Alzheimer's Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis.

The Impact of Cognitive Impairment on Clinical Outcomes After Transcatheter Aortic Valve Implantation (from a Systematic Review and Meta-Analysis).

This study sought to investigate the impact of pre-existing cognitive impairment on outcomes after transcatheter aortic valve implantation (TAVI). TAVI has been increasingly used in seniors, and evidence suggests better outcomes than surgical aortic valve replacement. Although frailty has been shown to be associated with poorer outcomes after TAVI, the effect of pre-existing cognitive impairment on patient outcomes after TAVI remains unclear. We searched the Medline, Embase, Scopus and Cochrane databases until May 14, 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was short-term (6 months to 1 year) mortality, and secondary outcomes included long-term (1 year to 3 years) mortality, in-hospital mortality, and postoperative delirium. A total of 14 studies with 32,746 patients (5,098 patients with cognitive impairment at baseline, 27,648 without) were included in our meta-analysis. Among studies that reported the raw proportion of patients with mortality of postoperative delirium, cognitive impairment significantly increased mortality (risk ratio 2.10, 95% confidence intervals [CIs] 1.43 to 3.08, p = 0.0002) and postoperative delirium (risk ratio 2.27, 95% CI 1.76 to 2.93, p <0.0001). Studies which reported the hazards for mortality (pooled hazards ratio 1.97, 95% CI 1.50 to 2.60, p <0.0001) and odds of postoperative delirium (pooled odds ratio 2.40, 95% CI: 1.51 to 3.80, p = 0.0002) yielded results consistent with the primary meta-analysis. In conclusion, pre-existing cognitive impairment is a significant risk factor for poorer outcomes after TAVI and should be carefully considered in this group of patients. Guidelines and future studies should take cognitive impairment into consideration for preoperative risk stratification.

Prevalence and incidence of stroke, white matter hyperintensities, and silent brain infarcts in patients with chronic heart failure: A systematic review, meta-analysis, and meta-regression.

Introduction: Heart failure (HF) is associated with ischemic stroke (IS). However, there are limited studies on the prevalence of IS, white matter hyperintensities (WMHs), and silent brain infarcts (SBIs). Furthermore, interaction with ejection fraction (EF) is unclear. Methods: We searched three databases (viz., PubMed, Embase, and Cochrane) for studies reporting the incidence or prevalence of IS, WMHs, and SBIs in HF. A total of two authors independently selected included studies. We used random-effects models, and heterogeneity was evaluated with I2 statistic. Meta-regression was used for subgroup analysis. Results: In total, 41 articles involving 870,002 patients were retrieved from 15,267 records. Among patients with HF, the pooled proportion of IS was 4.06% (95% CI: 2.94-5.59), and that of WMHs and SBIs was higher at 15.67% (95% CI: 4.11-44.63) and 23.45% (95% CI: 14.53-35.58), respectively. Subgroup analysis of HFpEF and HFrEF revealed a pooled prevalence of 2.97% (95% CI: 2.01-4.39) and 3.69% (95% CI: 2.34-5.77), respectively. Subgroup analysis of WMH Fazekas scores 1, 2, and 3 revealed a decreasing trend from 60.57 % (95% CI: 35.13-81.33) to 11.57% (95% CI: 10.40-12.85) to 3.07% (95% CI: 0.95-9.47). The relative risk and hazard ratio of patients with HF developing IS were 2.29 (95% CI: 1.43-3.68) and 1.63 (95% CI: 1.22-2.18), respectively. Meta-regression showed IS prevalence was positively correlated with decreasing anticoagulant usage. Conclusion: We obtained estimates for the prevalence of IS, WMH, and SBI in HF from systematic review of the literature. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255126, PROSPERO [CRD42021255126].

Prevalence and incidence of cognitive impairment and dementia in heart failure - A systematic review, meta-analysis and meta-regression.

INTRODUCTION: The burden of cognitive impairment in heart failure (HF) patients is significant and leads to longer hospital stay, higher readmission rates, and increased mortality. This review seeks to synthesize the available studies to determine the prevalence and incidence of cognitive impairment and dementia in HF patients. METHODS: PubMed, Embase, PsychoINFO, and Cochrane databases were systematically searched from their inception through to May 3, 2021. Study and population characteristics, total patients with HF, prevalence of cognitive impairment and dementia in HF patients, and cognitive assessment tool were abstracted by two reviewers. RESULTS: In HF patients, the overall prevalence for cognitive impairment and dementia was 41.42% (CI) and 19.79% (dementia), respectively. We performed a meta-regression analysis, which demonstrated that the risk of cognitive impairment and dementia increased with age. DISCUSSION: Further research should investigate whether HF accelerates the rate of cognitive decline and the progression of dementia.

Sodium-glucose cotransporter 2 inhibitors and neurological disorders: a scoping review.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of antidiabetic medications with a favourable cardiovascular, renal and overall safety profile. Given the limited treatment options available for neurological disorders, it is important to determine whether the pleiotropic effects of SGLT2i can be utilised in their prevention and management. Methods: All articles published before 20 March 2021 were systematically searched in MEDLINE, EMBASE, Scopus, Web of Science, APA PsycINFO and ClinicalTrials.gov. Overall, 1395 titles were screened, ultimately resulting in 160 articles being included in the qualitative analysis. Screening and data extraction were conducted by two independent authors and studies were excluded if they were not an original research study. Findings: Of the 160 studies, 134 addressed stroke, 19 cognitive impairment, 4 epilepsy and 4 movement disorders, encompassing a range from systematic reviews and randomised controlled trials to bioinformatic and animal studies. Most animal studies demonstrated significant improvements in behavioural and neurological deficits, which were reflected in beneficial changes in neurovascular units, synaptogenesis, neurotransmitter levels and target receptors' docking energies. The evidence from the minority clinical literature was conflicting and many studies did not reach statistical significance. Interpretation: SGLT2i may exert neurological benefits through three mechanisms: reduction in cardiovascular risk factors, augmentation of ketogenesis and anti-inflammatory pathways. Most clinical studies were observational, meaning that a causal relationship could not be established, while randomised controlled trials were heterogeneous and powered to detect cardiovascular or renal outcomes. We suggest that a longitudinal study should be conducted and specifically powered to detect neurological outcomes.

Cognitive Impairment in Heart Failure-A Review.

Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.

Novel Autoantibodies in Idiopathic Small Fiber Neuropathy.

OBJECTIVE: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high-throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS: Sera from 58 SFN patients and 20 age- and gender-matched healthy controls (HCs) were screened against >1,600 immune-related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS: Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). Further subgroup analysis into iSFN and SFN by secondary causes (secondary SFN) in the main cohort showed that MX1 is higher in iSFN compared to secondary SFN (FC = 1.61 vs 0.106, p = 0.009). INTERPRETATION: Novel autoantibodies MX1, DBNL, and KRT8 are found in iSFN. MX1 may allow diagnostic subtyping of iSFN patients. ANN NEUROL 2022;91:66-77.

A brief history of voxel-based grey matter analysis in Alzheimer's disease.

Voxel-based morphometry (VBM) and cortical thickness measurement are common techniques to identify regional atrophy in neurodegenerative diseases such as Alzheimer's disease (AD). Because studies employing these methods draw conclusions regarding patterns of regional cortical degeneration, it is important to be aware of their possible limitations. To evaluate the effect of different VBM versions, we performed voxel-based analyses through successive versions-from SPM99 to SPM8-as well as FSL-VBM on n = 20 AD patients and n = 20 controls. Reproducibility was assessed in an independent sample, again of n = 20 per group, from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Further, we tested the hypothesis that VBM can sensitively detect hippocampal atrophy, but is relatively insensitive to changes in the cortical ribbon, by contrasting VBM with FreeSurfer cortical thickness measurements. The results with both datasets confirmed that VBM preferentially identifies grey matter lesions in the mesial temporal lobe but is largely insensitive to isocortical atrophy. In contrast, FreeSurfer identified thinning of cortical ribbon association cortex more significant in post- rather than pre-Rolandic areas and with relative preservation of primary sensory-motor regions-in other words precisely as would be expected in AD. The results highlight a bias that VBM has toward detecting mesial temporal lobe atrophy. This finding has important implications for interpretation of clinical and cognitive studies in AD.