Accelerated vascular aging and persistent cognitive impairment in older female breast cancer survivors

Abstract

Advances in breast cancer treatment have markedly increased survivorship over the past three decades, with over 3.1 million survivors expected to live into their 70s and 80s. Without symptom relief interventions, nearly 35% of these survivors will have life-altering and distressing cognitive symptoms. This pilot study explored associations between serum markers of vascular aging, laterality in cerebral oxygenation, and severity of cognitive impairment in women, 12-18 months after chemotherapy for stage 2/3 invasive ductal breast cancer. Fifteen women (52-84 years) underwent a brief cognitive assessment (Montreal Cognitive Assessment [MOCA]) and blood draws to assess markers of vascular aging (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], and insulin growth factor-1 [IGF-1]). All underwent a computer-based test protocol that is known to increase blood flow within the frontal lobes. Percent cerebral oxyhemoglobin saturation (rcSO) was recorded during and after testing. Laterality in rcSO was defined by ≥ 3% difference between left and right rcSO (|rcSO mean mean|). Eight participants had MOCA scores between 21 and 25 points, suggestive of mild cognitive impairment. Neither CRP (r = -.24) nor IL-6 (r = .34) nor TNF-α (r = .002) were associated with MOCA scores. Higher IL-6 was associated with greater laterality (r = .41). MOCA scores were significantly lower in subjects with laterality in rcSO than in those without laterality (F = 13.5, p = 003). Lower IGF-1 was significantly associated with greater laterality (r = - .66, p = .007) and lower cognitive function (r = .58). These findings suggest that persistent cognitive impairment is associated with phenotypical changes consistent with accelerated vascular aging.

Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects

“…We hope that our findings will facilitate future endeavor of uncovering the mechanistic role of miRNA gene expression regulatory networks in the anti-aging effects of NAD+ booster treatments. Future studies should also investigate the links between miRNAs (Sullivan et al 2019) regulated by NMN and sirtuin activators and miRNAs known to act in the conserved pathways of aging (Ungvari et al 2018;Menghini et al 2014;Tarantini et al 2016b;Kennedy et al 2014;An et al 2017;Ashpole et al 2017;Bennis et al 2017;Deepa et al 2017;Fang et al 2017;Fulop et al 2018;Lee et al 2018;Reglodi et al 2018;Menghini et al 2009;Fan et al 2018) and major aging-related diseases (Csiszar et al 2017;Meschiari et al 2017;Tarantini et al 2017b;Tucsek et al 2017;Ungvari et al 2017b;Carlson et al 2018;Csipo et al 2018;Tana et al 2017;Feinberg and Moore 2016). Potentially, miRNA-regulated anti-aging mechanisms of NAD+ booster treatments and sirtuin activators could be harnessed for development of new pharmacological approaches for the prevention and treatment of age-related vascular diseases.…”

Age‐related alterations in the cerebrovasculature affect neurovascular coupling and BOLD fMRI responses: Insights from animal models of aging

“…Senescent astrocytes demonstrate increased levels of intermediate glial fibrillary acidic proteins and vimentin filaments, increased expression of pro‐inflammatory cytokines (including interleukin‐6 (Bhat et al., 2012)) and increased accumulation of proteotoxic aggregates which are thought to play a role in age‐related neuroinflammation and neuronal degeneration (Salminen et al., 2011). Importantly, anticancer treatments, including irradiation (Yabluchanskiy et al., 2020) and chemotherapy (Carlson et al., 2018) can cause neurovascular senescence, which associate with significant impairment of neurovascular coupling responses.…”

Assessment of age-related decline of neurovascular coupling responses by functional near-infrared spectroscopy (fNIRS) in humans

“…Application of fNIRS-based NVC measurements in self-controlled observational study designs, such as the case-crossover design and the self-controlled case series, is particularly promising. fNIRS may also be a useful tool to test the underlying causes of treatment-associated deteriorations of cognitive function as it is with chemotherapy (Carlson et al 2018) and whole-brain irradiation (Ungvari et al 2017;Warrington et al 2013), which will provide a tool for a development of better and safer medications to tackle these complications in aging.…”