Emine PETEKKAYA, Zülal KAPTAN, Demet ÜNALMIŞ, Gülen BURAKGAZİ, Berna KUŞ, İsmet Murat MELEK, Abdullah ARPACI

An investigation of olfactory bulb and entorhinal cortex volumes in both patients with Alzheimer’s disease and healthy individuals, and a comparative analysis of neuropeptides

Alzheimer’s Disease (AD) is the most common neurodegenerative disease and is hard to diagnose at the early stages. The pathogenesis of AD is associated with the loss of a sense of smell. Reduction in the volumes of the Olfactory Bulb (OB) and Entorhinal Cortex (EC) is positively correlated with the decline of the smelling function where OB projects to EC. This study aims to detect the early changes in OB and EC volumes in AD patients by comparing them to healthy subjects. This study also aims to make a comparative analysis of plasma levels and the relationship between arginine-vasopressin (AVP) and Oxytocin (OT), which are neuropeptides associated with cognitive functions. The participants comprised 9 AD patients and 12 healthy individuals. We used volumetric methods such as MRICloud and IBASPM to measure the OB and EC volumes with the help of 3D MRI (Magnetic Resonance Imaging) images. We compared the left and right differentiation. Moreover, we investigated the neuropeptide levels in blood samples from the participants. We conducted a correlation analysis for all parameters. Bilateral OB atrophy was discovered in the AD patients in comparison to the control group (p=0.002 for right; p=0.015 for left). The right OB volume was measured to be larger than the left OB volume in the control group,but this asymmetry was not observed in the AD patients. The right and left EC's of the AD patients were atrophic in comparison to the control (p

PDF

___

1. Marin C, Vilas D, Langdon C, et al. Olfactory dysfunction in neurodegenerative diseases. Curr Allergy Asthma Rep. 2018;18:42.

2. Jung HJ, Shin IS, Lee JE. Olfactory function in mild cognitive impairment and Alzheimer's disease: A meta-analysis. Laryngoscope. 2019;129:362-9.

3. Bathini P, Brai E, Auber LA. Olfactory dysfunction in the pathophysiological continuum of dementia. Ageing Res Rev. 2019;55:100956.

4. Murphy C. Olfactory and other sensory impairments in Alzheimer disease. Nat Rev Neurol. 2019;15:11-24.

5. DeVere R. Disorders of taste and smell. Continuum. 2017;23:421-46.

6. Daulatzai MA. Olfactory dysfunction: its early temporal relationship and neural correlates in the pathogenesis of Alzheimer's disease. J Neural Transm. 2015;122:1475-97.

7. Lu J, Wang X, Qing Z, et al. Detectability and reproducibility of the olfactory fMRI signal under the influence of magnetic susceptibility artifacts in the primary olfactory cortex. Neuroimage. 2018;178:613-21.

8. Asal N, Bayar Muluk N, Inal M, et al. Olfactory bulbus volume and olfactory sulcus depth in psychotic patients and patients with anxiety disorder/ depression. Eur Arch Otorhinolaryngol. 2018;275:3017-24.

9. Gellrich J, Han P, Manesse C, et al. Brain volume changes in hyposmic patients before and after olfactory training. Laryngoscope. 2018;128:1531-6.

10. Chapuis J, Cohen Y, He X, et al. Lateral entorhinal modulation of piriform cortical activity and fine odour discrimination. J Neurosci. 2013;33:13449-59.

11. Fliers E, Swaab DF, Pool CW, et al. The vasopressin and oxytocin neurons in the human supraoptic and paraventricular nucleus; changes with aging and in senile dementia. Brain Res. 1985;342:45-53.

12. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on alzheimer’s disease. Neurology. 1984;34:939–44.

13. Acer N, Turgut M. Measurements of the insula volume using MRI. Island Reil Human Brain. 2018;101-11.

14. Han SH, Lee MA, An SS, et al. Diagnostic value of Alzheimer's diseaserelated individual structural volume measurements using IBASPM. J Clin Neurosci. 2014;21:2165-9.

15. Lucassen PJ, Tilders FJ, Salehi A, et al. Neuropeptides vasopressin (AVP), oxytocin (OXT) and corticotropin-releasing hormone (CRH) in the human hypothalamus: activity changes in aging, Alzheimer's disease and depression. Aging. 1997;9:48-50.

16. Meynen G, Unmehopa UA, van Heerikhuize JJ, et al. Increased arginine vasopressin mRNA expression in the human hypothalamus in depression: A preliminary report. Biol Psychiatry. 2006;60:892-5.

17. Lieberwirth C, Wang Z. Social bonding: regulation by neuropeptides. Front Neurosci. 2014;8:171.

18. Sayılır S, Çullu N. Decreased olfactory bulb volumes in patients with fibromyalgia syndrome. Clin Rheumatol. 2017;36:2821-4.

19. Rombaux P, Grandin C, Duprez T. How to measure olfactory bulb volume and olfactory sulcus depth? B-ENT. 2009;5:53-60.

20. Thomann PA, Dos Santos V, Seidl U, et al. MRI-derived atrophy of the olfactory bulb and tract in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis. 2009;17:213-21.

21. Altunisik E, Baykan AH. Comparison of the olfactory bulb volume and the olfactory tract length between patients diagnosed with essential tremor and healthy controls: findings in favor of neurodegeneration. Cureus. 2019;11:e5846.

22. Doğan A, Bayar Muluk N, Şahan MH, et al. Olfactory bulbus volume and olfactory sulcus depth in migraine patients: an MRI evaluation. Eur Arch Otorhinolaryngol. 2018;275:2005-11.

23. Doğan A, Bayar Muluk N, Şahin H. Olfactory bulb volume and olfactory sulcus depth in patients with OSA: an MRI evaluation. Ear Nose Throat J. 2019;99:442-7.

24. Suzuki M, Takashima T, Kadoya M, et al. MR imaging of olfactory bulbs and tracts. AJNR Am J Neuroradiol. 1989;10:955-7.

25. Yousem DM, Geckle RJ, Bilker WB, et al. Olfactory bulb and tract and temporal lobe volumes. Normative data across decades. Ann N Y Acad Sci. 1998;855:546-55.

26. Oliveira-Pinto AV, Santos RM, Coutinho RA, et al. Sexual dimorphism in the human olfactory bulb: females have more neurons and glial cells than males. PLoS One. 2014;9:e111733.

27. Yu H, Hang W, Zhang J, et al. [Olfactory function in patients with Alzheimer' disease]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015;29:444-7.

28. Aktürk T, Tanık N, Serin Hİ, et al. Olfactory bulb atrophy in migraine patients. Neurol Sci. 2019;40:127-32.

29. Van Hoesen GW, Hyman BT, Damasio AR. Entorhinal cortex pathology in Alzheimer's disease. Hippocampus. 1991;1:1-8.

30. Grundwald NJ, Benítez DP, Brunton PJ. Sex-Dependent effects of prenatal stress on social memory in rats: a role for differential expression of central vasopressin-1a receptors. J Neuroendocrinol. 2016;28.

31. Insausti R, Juottonen K, Soininen H, et al. MR volumetric analysis of the human entorhinal, perirhinal, and temporopolar cortices. AJNR Am J Neuroradiol. 1998;19:659-71.

32. Oettl LL, Ravi N, Schneider M, et al. Oxytocin enhances social recognition by modulating cortical control of early olfactory processing. Neuron. 2016;90:609-21.

33. Wang Y, Hao L, Zhang Y, et al. Entorhinal cortex volume, thickness, surface area and curvature trajectories over the adult lifespan. Psychiatry Res Neuroimaging. 2019;292:47-53.

34. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol. 1991;82:239-59.

35. Arriagada PV, Growdon JH, Hedley-Whyte ET, et al. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology. 1992;42:631-9.

36. Mitre M, Minder J, Morina EX, et al. Oxytocin modulation of neural circuits. Curr Top Behav Neurosci. 2018;35:31-53.

37. Sasaki T, Hashimoto K, Oda Y, et al. Decreased levels of serum oxytocin in pediatric patients with attention deficit/hyperactivity disorder. Psychiatry Res. 2015;228:746-51.

38. Buijs RM, Swaab DF, Dogterom J, et al. Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat. Cell Tissue Res. 1978;186:423-33.

39. Fujiyoshi K, Suga H, Okamoto K, et al. Reduction of arginine-vasopressin in the cerebral cortex in Alzheimer type senile dementia. J Neurol Neurosurg Psychiatry. 1987;50:929-32.

40. Sørensen PS, Hammer M, Vorstrup S, et al. CSF and plasma vasopressin concentrations in dementia. J Neurol Neurosurg Psychiatry. 1983;46:911-6.