Chronic cerebral hypoperfusion lacks and operative definition. Defined clinical conditions are thought to cause chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion is linked to neurocognitive disorders. Neuroimaging lesions are seen in animal models and in clinical conditions.
From June 2020.
Accumulation of Ab, either because of increased production or altered clearance, increases arterial vasoconstriction, reduces resting cerebral blood flow (CBF) and impairs functional hyperemia.
The available data support a conceptual framework that considers chronic cerebral hypoperfusion a likely, relevant pathogenic mechanism for the neurodegeneration-like progression of the neurocognitive disorders. The relationship between neuropathology, cerebral perfusion, and symptoms progression is, however, elusive for several aspects.
it is unclear whether changes in CBF precede or follow the neurovascular dysfunction, or whether the hypoperfusion is a cause or a consequence, or just an epiphenomenon.
Epidemiological data, by showing the co-presence of vascular risk factors and neurocognitive disorders, support the causal link between vascular and neurodegenerative mechanisms. For instance, major and mild neurocognitive disorders due to AD are consistently associated with vascular risk factors such as hypertension, ischemic heart disease, hypercholesterolemia, atrial fibrillation, smoking and obesity. Whether the association is a causal one is uncertain. Still, in large population-based studies, the CBF reduction precedes the cognitive decline and hippocampal atrophy as to suggest a causality.
Most notably, CCH is generally inferred, not measured.
Thus, hypoperfusion encompasses many different conditions, which range from mild phasic or temporary mismatch between energy tissue demand and blood flow supply to a persistent inadequate perfusion. An operative definition of hypoperfusion is, therefore, missing.
Since the amount of oxygen stored in brain is small, an increase in CBF is mandatory whenever there is increased energy demand. The exploitation of several methods and techniques for measuring local rates of CBF and energy metabolism under a variety of physiological conditions has shown that rates of CBF and energy metabolism are heterogeneously distributed within the brain.
CCH seems, therefore, to refer to inadequate supply of nutrients (essentially, glucose and oxygen) to meet the energy demand of the tissue, including conditions of altered functional hyperemia. The mismatch results in increased extraction of oxygen, from the blood, by the brain, at least in the early phases when the brain function is maintained normal (or near normal) despite the reduced perfusion.
[On animal studies]
Neural and synaptic contact loss may occur later and may not correlate with CBF changes. The 2VO animals develop behavioral changes, which share similarities with the cognitive disorders in humans. The behavioral alterations are measurable a few weeks following occlusion and seem to progress with time, even when flow has recovered to normal values. Thus, while most of the changes occur during the chronic phase of the hypoperfusion, the progression of the behavioral changes seems to support the hypothesis of a neurodegenerative-like mechanism that may ‘‘survive” to the hypoperfusion.
The term ‘‘cardiogenic dementia” appeared in the literature almost forty years ago and since than several findings have supported the association between HF and cognitive impairment. In a case-control study Sauvé et al. found that in subjects with HF there is a 4-fold increased risk of cognitive impairment as compared to matched controls. In a prospective cohort study of a total of 577 patients, 79% of them resulted impaired at least in one cognitive domain. In a meta-analysis Cannon et al. estimated a 40% prevalence of cognitive impairment in subjects with HF, thus confirming the association between HF and cognitive impairment.
The pathophysiological mechanism behind this relationship is, however, unclear. It is a question whether the hypoperfusion per se, and the consequent hypoxia, is the cause of the neurocognitive disorders. A few studies, carried out in small groups of patients who underwent heart transplant, reported partial recovery of neuropsychological performances following intervention, supporting the clinical relevance of the improved cerebral perfusion. Other variables, however, including changes in cerebrovascular reactivity, potentially associated with endothelial dysfunction or coagulation, are also relevant.
Research is mainly focused on essential hypotension or orthostatic hypotension (OH). The essential hypotension (also named constitutional, primary or chronic hypotension) is a persistent condition of lowered blood pressure (BP) without any identifiable pathological factors. In most studies, however, there is not defined. BP threshold value, and hypotension is often defined in association with symptoms such as fatigue, dizziness and concentration deficits.
...hypotension is thought to cause failure of the CBF autoregulation.
The findings altogether suggest that different diseases that cause altered blood perfusion of the brain promote neurodegeneration. Several mechanisms are involved in mediating the effect of hypoperfusion. Most of the reported mechanisms refer to dysfunctions of the NVU, which may or may not cause hypoxia. An open question, therefore, regards the role of hypoxia. A few studies report an increased risk of neurocognitive disorders in subjects with anemia or chronic obstructive pulmonary disease suggesting that hypoxia per se, i. e. without the traditional cerebrovascular risks and apparently without defects in perfusion, causes, or contributes to, the neurocognitive disorders.
