Presence of cerebral microbleeds is associated with cognitive decline in acromegaly

Abstract

BackgroundCognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. MethodsIn a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3 days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored.ResultsThe incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p < 0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p < 0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR = 3.19, 95% CI 1.51–6.76, p = 0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR = 13.34, 95% CI 3.09–57.51, p = 0.001).ConclusionsA significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly.

Glymphatic transport is reduced in rats with spontaneous pituitary tumor

“…By causing abnormal hormone levels (74, 75) and metabolic derangements (5,12,76), pituitary tumor poses an excess risk of unfavorable alterations in the cerebrovascular network, structurally and functionally affecting both large and small vessels. The elevated cerebrovascular events include arteriosclerosis and atherosclerosis pathologies, high blood pressure, cerebral infarcts and cerebral microbleeds (17,18,77,78) that diffusely disturb the proper functioning of vascular and peri-vascular transport. In line with these well-recognized changes in the cerebrovascular system, our image data revealed an occluded glymphatic influx pathway (e.g., partially enhanced circle of Willis; Figure 3) that obstructed CSF movement, representing damaged peri-vascular transport along the large arterial vessel.…”

“…In addition to a mass effect on nearby brain tissue and cranial nerve structures (3,4), pituitary tumor induced endocrine dysfunction plays an important role in affecting brain function (5)(6)(7). Cumulative data demonstrate that hormonal disorders caused by pituitary tumors contribute to structural alterations (7)(8)(9)(10), metabolic abnormalities (11)(12)(13)(14) and cerebrovascular disease (15)(16)(17)(18) that are accompanied by a wide variety of adverse neuropsychological symptoms and neurocognitive consequences (1,(19)(20)(21)(22) in patients. Although the underlying mechanisms leading to neurocognitive deficits in patients with pituitary tumors remain to be fully elucidated, growing evidence suggests that aberrant hormone secretion may be a major factor for cognitive impairment (11,22,23).…”

“…Moreover, cerebrovascular pathology (e.g., cerebral infarction) arising from non-functioning pituitary tumor is independent of hormone replacement therapy (28), and cerebrovascular mortality remains elevated in the treated patients regardless of post-treatment hormone levels (18,29). These findings suggest that tumor-induced deleterious impact on the central nervous system (CNS) and cerebral vasculature that are linked to the decline of cognitive function (17,(30)(31)(32) persists after resolution of hormone abnormalities, and at the same time, indicate that factors other than hormone imbalance, that act particularly upon the cognitive impairment, are likely at work.…”