Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people

Sorond, Farzaneh A.; Hurwitz, Shelley; Salat, David H.; Greve, Douglas N.; Fisher, Naomi D.L.

doi:10.1212/wnl.0b013e3182a351aa

Cited by 117 publications

(101 citation statements)

References 20 publications

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“…There is growing evidence that vascular contributions to cognitive impairment and dementia (VCID) are critical in aging . Among them, impaired neurovascular coupling responses (Fabiani et al 2013;Park et al 2007;Stefanova et al 2013;Topcuoglu et al 2009;Toth et al 2014a;Zaletel et al 2005) are thought to importantly contribute to the cognitive decline (Sorond et al 2013) in the elderly. From the results of this study and from recent findings by other laboratories (Warrington et al 2013), the picture emerges that WBI-induced DNA damage responses induce an accelerated aging-like phenotype in the neurovascular The somatosensory evoked potential responses in the somatosensory cortex evoked by contralateral whisker pad stimulation are comparable in control and WBI-treated mice.…”

Section: Discussionmentioning

confidence: 99%

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

et al. 2017

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Whole brain irradiation (WBI) is a mainstream therapy for patients with both identifiable brain metastases and prophylaxis for microscopic malignancies. However, it also promotes accelerated senescence in healthy tissues and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long term after treatment, due to γ-irradiation-induced cerebromicrovascular injury. Moment-to-moment adjustment of cerebral blood flow ( C B F ) v i a n e u r o n a l a c t i v i t y -d e p e n d e n t cerebromicrovascular dilation (functional hyperemia) has a critical role in maintenance of healthy cognitive function. To determine whether cognitive decline induced by WBI associates with impaired cerebromicrovascular function, C56BL/6 mice (3 months) subjected to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks) and control mice were compared. Mice were tested for spatial memory performance (radial arm water maze), sensorimotor coordination (computerized gait analysis, CatWalk), and cerebromicrovascular function (whisker-stimulation-induced increases in CBF, measured by laser Doppler flowmetry) at 3 to 6 months post-irradiation. We found that mice with WBI exhibited impaired cerebromicrovascular function at 3 months post-irradiation, which was associated with impaired performance in the radial arm water maze. At 6 months, post-irradiation progressive impairment in gait coordination (including changes in the regularity index and phase dispersion) was also evident. Collectively, our findings provide evidence for early and persisting neurovascular impairment after a clinically relevant protocol of fractionated WBI, which predict early manifestations of cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

et al. 2017

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“…The resulting functional hyperemia is responsible for maintenance of an optimal local microenvironment in the cerebral tissue by increasing delivery of oxygen and glucose and removal of potentially deleterious by‐products of cerebral metabolism. Aging is associated with significant impairment of functional hyperemia (termed ‘neurovascular uncoupling’), and the ensuing disruption of the cerebral microenvironment likely contributes to impairment of higher cerebral function in elderly patients and aged laboratory animals (Zaletel et al ., 2005; Park et al ., 2007; Topcuoglu et al ., 2009; Fabiani et al ., 2013; Sorond et al ., 2013; Stefanova et al ., 2013; Toth et al ., 2014a). Yet, the specific age‐related mechanisms responsible for neurovascular uncoupling are not yet understood.…”

Section: Introductionmentioning

confidence: 99%

IGF‐1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging

et al. 2015

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SummaryAging is associated with marked deficiency in circulating IGF‐1, which has been shown to contribute to age‐related cognitive decline. Impairment of moment‐to‐moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age‐related cognitive impairment. To establish the link between IGF‐1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF‐1 deficiency (Igf1 f/f‐TBG‐Cre‐AAV8) and accelerated vascular aging. We found that IGF‐1‐deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal‐dependent spatial memory test, mimicking the aging phenotype. IGF‐1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF‐1 deficiency also impaired glutamate‐mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF‐1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment.

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“…If this is the case, then it could be proposed that even subclinical impairment of neurovascular function in aging may exacerbate the complex gait abnormalities in older patients. In that regard, it is important to point out that in aging, and age-related pathophysiological conditions (e.g., hypertension), neurovascular uncoupling often co-occurs with other microvascular pathophysiological alterations (e.g., microhemorrhages (Ungvari et al 2017b), white matter hyperintensities (Sorond et al 2013)), which are also known to cause gait abnormalities (Toth et al 2015c). It should be thus emphasized that specific patterns of gait variability may imply different underlying causes (Brach et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, impaired neurovascular coupling responses in the elderly were shown to associate with impaired higher cognitive function (Sorond et al 2013). Experimental studies in mouse models with pharmacological inhibition of the synthesis of NO, EETs, and prostaglandins confirm that a causal link exists between neurovascular dysfunction and cognitive impairment.…”

Section: Introductionmentioning

confidence: 97%

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

et al. 2017

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There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To establish a direct cause-andeffect relationship between impaired NVC and gait abnormalities, we induced neurovascular uncoupling pharmacologically in young C57BL/6 mice by inhibiting the synthesis of vasodilator mediators involved in NVC. Treatment of mice with the epoxygenase inhibitor MSPPOH, the NO synthase inhibitor L-NAME, and the COX inhibitor indomethacin significantly decreased NVC mimicking the aging phenotype. Pharmacologically induced neurovascular uncoupling significantly decreased the dynamic gait parameter duty cycle, altered footfall patterns, and significantly increased phase dispersion, indicating impaired interlimb coordination. Impaired NVC also tended to increase gait variability. Thus, selective experimental disruption of NVC causes subclinical gait abnormalities, supporting the importance of CBF in both cognitive function and gait regulation.

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Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people

Abstract: There is a strong correlation between neurovascular coupling and cognitive function, and both can be improved by regular cocoa consumption in individuals with baseline impairments. Better neurovascular coupling is also associated with greater white matter structural integrity.

Cited by 117 publications

References 20 publications

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

IGF‐1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

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