Vascular Dysfunction Compromises Cognition in Hyperparathyroidism
Treatment of PHPT improved some areas of cognition.
Primary hyperparathyroidism (PHPT) may be linked to lower intracerebral vasomotor reactivity (VMR), which may result in cognitive dysfunction, according to study results presented at the American Society for Bone and Mineral Research (ASBMR) 2017 Annual Meeting, held September 8-11, in Denver, Colorado.
Although it has been previously reported that parathyroidectomy (PTX) can reverse cognitive dysfunction associated with PHPT, it is not clear how parathyroid hormone (PTH)-dependent intracerebral vascular dysfunction may adversely affect blood flow and cognition in PHPT.
In the current study, Minghao Liu, MD, of Columbia University Medical Center in New York, enrolled 20 women with PHPT who underwent PTX and healthy control subjects. The participants underwent cognitive testing, functional magnetic resonance imaging (MRI), and transcranial Doppler ultrasound to measure VMR before PTX and 6 months after PTX. Overall, participants with PHPT had mild disease (calcium 10.6±0.5 mg/dL, PTH 93±42 pg/mL), normal mean vitamin D levels, and normal renal and thyroid function. At baseline, mood and age-, sex-, and education-adjusted scores for visuospatial memory, verbal memory, and motor speed were within normal limits.
Notably, VMR was worse in patients with PHPT compared with control subjects (3.2%±0.9% vs 4.2%±1.1% mm Hg PCO2; P =.03), but was not found to be associated with PTH (r=0.28; P =.43) or calcium levels (r=0.32; P =.36). Functional MRI showed reduced neuronal activation in the cerebellum during matrix reasoning (t=32, k=179 voxels; P <.001) and increased activation in the cingulate gyrus (t=14, k=26; P <.001) in patients with PHPT vs 18 age- and sex-matched control subjects. In addition, neuronal activation in patients with PHPT was inversely correlated with PTH levels in the cingulate gyrus (r=-0.77, t=14, k=26), positively correlated with PTH levels in the frontal gyrus (r=0.84, t=15, k=21), and positively correlated with calcium in the caudate (r=0.87, t=14, k=62) and frontal gyrus (r=0.79,t=14, k=24; all P <.0001).
Ultimately, 15 patients with PHPT underwent PTX. After the procedure, scores for visual memory (-0.07±1.56 vs 0.61±1.78; P =.03), verbal fluency (-0.16±0.94 vs 0.31±1.26; P =.03), motor speed (-0.56±1.23 vs 0.2±1.2; P =.03), and mood (12±10 vs 8±6; P =.04) improved; however, no change was observed in VMR (n=8; 3.4±0.9 vs 3.7±1.0; P =.52). Notably, patients who underwent PTX had a reduction in neuronal activation during nonverbal abstraction and verbal memory.
Overall, the findings suggest that PHPT may be associated with reduced VMR, which may contribute to cognitive dysfunction. Treatment of PHPT improved some areas of cognition; however, further research is required to determine if VMR indeed improves after PTX, and if it affects cognitive function in patients with PHPT.
Sum M, Gazes Y, Mariana B, et al. Primary hyperparathyroidism: role of impaired cerebrovascular function in cognitive symptoms. Presented at: American Society for Bone and Mineral Research (ASBMR) 2017 Annual Meeting. September 8-11, 2017; Denver, CO. Abstract FR0007.