Obesity is one of the factors associated with cognitive impairment. However, obesity may differently affect cognitive function in different age groups, and scarce data are available from low- and middle-income countries. This cross-sectional study aimed to identify the association between obesity and cognitive impairment among 143 elderly individuals in Yogyakarta. We recorded the sociodemographic factors and some comorbidities, also measured the body mass index as a parameter of obesity, cognitive function using Montreal Cognitive Assessment—Indonesia, mood condition and depression status using geriatric depression scale-short form, as well as the daily life function using Activity of Daily Living and Instrumental Activity of Daily Living. After adjustment for the sociodemographic and comorbidities, we found that subjects with older age were more likely to have cognitive impairment (odds ratio [OR] 3.544, 95%CI: 1.36–9.22, p < 0.01) and compared with elderly individuals with normal weight, obese elderly individuals were 40% less likely to have cognitive impairment (OR 0.604, 95%CI: 0.39–0.95, p < 0.05). This study suggests that obesity in elderly individuals is less frequently associated with cognitive impairment. These findings support the reverse causation mechanism related to body mass index (BMI) and cognitive impairment in low/middle-income countries.

Background Serum vascular endothelial growth factor (VEGF) and infarct volume detected by brain imaging have been associated with stroke outcome. However, the relationship of these two variables with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between acute serum VEGF levels and infarct volume with PSCI in ischemic stroke patients.

Vascular dementia (VaD) is the second most common cause of dementia, but the treatment is still lacking. Although many studies have reported that histone deacetylase inhibitors (HDACis) confer protective effects against ischemic and hypoxic injuries, their role in VaD is still uncertain. Previous studies shown, one HDACi protected against cognitive decline in animals with chronic cerebral hypoperfusion (CCH). However, the underlying mechanisms remain elusive. In this study, we tested several 10,11‐dihydro‐5H‐dibenzo[b,f]azepine hydroxamates, which act as HDACis in the CCH model (in vivo), and SH‐SY5Y (neuroblastoma cells) with oxygen‐glucose deprivation (OGD, in vitro). We identified a compound 13, which exhibited the best cell viability under OGD. The compound 13 could increase, in part, the protein levels of brain‐derived neurotrophic factor (BDNF). It increased acetylation status on lysine 14 residue of histone 3 (H3K14) and lysine 5 of histone 4 (H4K5). We further clarified which promoters (I, II, III, IV or IX) could be affected by histone acetylation altered by compound 13. The results of chromatin immunoprecipitation and Q‐PCR analysis indicate that an increase in H3K14 acetylation leads to an increase in the expression of BDNF promoter II, while an increase in H4K5 acetylation results in an increase in the activity of BDNF promoter II and III. Afterwards, these cause an increase in the expression of BDNF exon II, III and coding exon IX. In summary, the HDACi compound 13 may increase BDNF specific isoforms expression to rescue the ischemic and hypoxic injuries through changes of acetylation on histones.

The pathophysiology of vascular cognitive impairment (VCI) is associated with chronic cerebral hypoperfusion (CCH). Increased high-mobility group box protein 1 (HMGB1), a nonhistone protein involved in injury and inflammation, has been established in the acute phase of CCH. However, the role of HMGB1 in the chronic phase of CCH remains unclear. We developed a novel animal model of CCH with a modified bilateral common carotid artery occlusion (BCCAO) in C57BL/6 mice. Cerebral blood flow (CBF) reduction, the expression of HMGB1 and its proinflammatory cytokines (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β, and IL-6), and brain pathology were assessed. Furthermore, we evaluated the effect of HMGB1 suppression through bilateral intrahippocampus injection with the CRISPR/Cas9 knockout plasmid. Three months after CCH induction, CBF decreased to 30–50% with significant cognitive decline in BCCAO mice. The 7T-aMRI showed hippocampal atrophy, but amyloid positron imaging tomography showed nonsignificant amyloid-beta accumulation. Increased levels of HMGB1, TNF-α, IL-1β, and IL-6 were observed 3 months after BCCAO. HMGB1 suppression with CRISPR/Cas9 knockout plasmid restored TNF-α, IL-1β, and IL-6 and attenuated hippocampal atrophy and cognitive decline. We believe that HMGB1 plays a pivotal role in CCH-induced VCI pathophysiology and can be a potential therapeutic target of VCI.