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Alzheimer hastalığında transkraniyal manyetik stimülasyonun hipokampal alt alanlar üzerindeki yapısal etkileri

Year 2025, Volume: 30 Issue: 1, 62 - 70, 29.01.2025
https://doi.org/10.21673/anadoluklin.1595288

Abstract

Amaç: Bu çalışma, Alzheimer hastalığı (AH) olan bireylerde tekrarlayan transkraniyal manyetik stimülasyonun (rTMS) hipokampal alt alanlar ve kortikal şekil metrikleri üzerindeki yapısal etkilerini araştırmaktadır. Yüksek çözünürlüklü MRI segmentasyonu ve Hippunfold analizi kullanılarak, TMS kaynaklı yapısal değişiklikleri incelemeyi ve TMS’nin olası nöroprotektif rolünü değerlendirmeyi amaçlıyoruz.

Yöntemler: Bu retrospektif çalışmada, 17 AH hastası ve 18 sağlıklı kontrol (SK) yer aldı. AH hastalarına, iki hafta boyunca toplam 10 seanslık sol lateral paryetal korteksi hedefleyen 20 Hz rTMS uygulandı. Tedavi öncesi ve sonrası MRI görüntüleri Hippunfold yazılımıyla analiz edilerek hipokampal alt alanlar segmentlendi ve kortikal kalınlık ile şekil metrikleri çıkarıldı. Gruplar arası ve zaman noktaları arasındaki karşılaştırmalar için istatistiksel analizler yapıldı.

Bulgular: Hipokampal volumetrik analiz, AH hastalarında Cornu Ammonis 1, (CA1), CA2, CA4, dentat girus (DG), subikulum ve stratum radiatum-lacunosum-moleculare (SRLM) gibi alt alanlarda belirgin atrofi olduğunu ortaya koydu. TMS sonrası anlamlı bir volumetrik iyileşme gözlenmese de, sağ CA3 alt alanında progresif atrofi tespit edildi (p=0.005). Kortikal şekil analizleri, AH hastalarında hipokampal kalınlıkta (p<0.001) ve yüzey alanında (p<0.001) sağlıklı kontrollere kıyasla anlamlı azalmalar olduğunu gösterdi ve her iki hemisferde de TMS öncesi ve sonrası arasında kortikal incelme görüldü. Bu bulgular, TMS tedavisine rağmen devam eden nörodejenerasyonu işaret etmektedir.

Sonuç: TMS, bu çalışmada hipokampal atrofiyi veya kortikal incelmeyi anlamlı şekilde tersine çevirmemiştir. Ancak, sol hipokampal alt alanların sağa göre daha stabil olması, TMS’nin potansiyel nöroprotektif etkilerini işaret etmektedir. Bu sonuçlar, TMS’nin AH progresyonunu hafifletme potansiyelini araştırmak için daha uzun süreli ve çift taraflı stimülasyon protokollerinin gerekliliğine dikkat çekmektedir.

References

  • Doran S, Carey D, Knight S, Meaney JF, Kenny RA, De Looze C. Relationship between hippocampal subfield volumes and cognitive decline in healthy subjects. Front Aging Neurosci. 2023;15:1284619.
  • Tarawneh R, Holtzman DM. The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb Perspect Med. 2012;2(5):a006148.
  • Yan Y, Tian M, Wang T, Wang X, Wang Y, Shi J. Transcranial magnetic stimulation effects on cognitive enhancement in mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Front Neurol. 2023;14:1209205.
  • Bashir S, Uzair M, Abualait T, et al. Effects of transcranial magnetic stimulation on neurobiological changes in Alzheimer’s disease (Review). Mol Med Rep. 2022;25(4):109.
  • Wei L, Zhang Y, Wang J, et al. Parietal-hippocampal rTMS improves cognitive function in Alzheimer’s disease and increases dynamic functional connectivity of default mode network. Psychiatry Res. 2022;315:114721.
  • Jung YH, Jang H, Park S, et al. Effectiveness of Personalized Hippocampal Network-Targeted Stimulation in Alzheimer Disease: A Randomized Clinical Trial [published correction appears in JAMA Netw Open. 2024;7(7):e2426187.
  • Velioglu HA, Hanoglu L, Bayraktaroglu Z, et al. Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer’s disease: Possible role of BDNF and oxidative stress. Neurobiol Learn Mem. 2021;180:107410.
  • DeKraker J, Haast RAM, Yousif MD, et al. Automated hippocampal unfolding for morphometry and subfield segmentation with HippUnfold. Elife. 2022;11:e77945.
  • Wang JX, Rogers LM, Gross EZ, et al. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014;345(6200):1054-7.
  • Mencarelli L, Torso M, Borghi I, et al. Macro and micro structural preservation of grey matter integrity after 24 weeks of rTMS in Alzheimer’s disease patients: a pilot study. Alzheimers Res Ther. 2024;16(1):152.
  • Suthana NA, Ekstrom AD, Moshirvaziri S, Knowlton B, Bookheimer SY. Human hippocampal CA1 involvement during allocentric encoding of spatial information. J Neurosci. 2009;29(34):10512-9.
  • Mu Y, Gage FH. Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener. 2011;6:85.
  • Kricheldorff J, Göke K, Kiebs M, et al. Evidence of Neuroplastic Changes after Transcranial Magnetic, Electric, and Deep Brain Stimulation. Brain Sci. 2022;12(7):929.
  • Jack CR Jr, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207-16.
  • Heine J, Prüß H, Scheel M, et al. Transdiagnostic hippocampal damage patterns in neuroimmunological disorders. Neuroimage Clin. 2020;28:102515.
  • Shen KK, Fripp J, Mériaudeau F, et al. Detecting global and local hippocampal shape changes in Alzheimer’s disease using statistical shape models. Neuroimage. 2012;59(3):2155-66.

The structural effects of transcranial magnetic stimulation on hippocampal subfields in Alzheimer's disease

Year 2025, Volume: 30 Issue: 1, 62 - 70, 29.01.2025
https://doi.org/10.21673/anadoluklin.1595288

Abstract

Aim: This study investigates the structural effects of repetitive transcranial magnetic stimulation (rTMS) on hippocampal subfields and cortical shape metrics in Alzheimer’s disease (AD) patients. Using high-resolution MRI segmentation and analysis via Hippunfold, we aim to elucidate TMS-induced structural changes and assess its potential neuroprotective role.

Methods: This retrospective study included 17 AD patients and 18 healthy controls (HC). AD patients underwent 20 Hz rTMS targeting the left lateral parietal cortex over 10 sessions across two weeks. Magnetic resonance imaging (MRI) data were acquired before and after rTMS and analyzed with Hippunfold to segment hippocampal subfields and extract cortical thickness and shape metrics. Statistical analyses were performed to compare subfield volumes and cortical metrics between groups and across time points.

Results: Hippocampal volumetric analysis revealed significant atrophy in subfields such as Cornu Ammonis 1, (CA1), CA2, CA4, dentate gyrus (DG), subiculum, and stratum radiatum-lacunosum-moleculare (SRLM) in AD patients compared to HC. Although no significant volumetric recovery was observed post-TMS, a further decline was noted in the right CA3 subfield (p=0.005), highlighting progressive atrophy. Cortical shape analyses showed significant reductions in hippocampal thickness (p<0.001) and surface area (p<0.001) in AD patients versus HC, with further cortical thinning in both hemispheres between pre- and post-TMS conditions. These findings suggest ongoing neurodegeneration despite TMS treatment.

Conclusion: TMS did not significantly reverse hippocampal atrophy or cortical thinning in this cohort. However, observed asymmetry in atrophy patterns, with relatively stable left hippocampal subfields compared to the right, suggests potential neuroprotective effects of TMS. These results highlight the need for prolonged and bilateral stimulation protocols to explore the therapeutic potential of TMS in mitigating AD progression.

References

  • Doran S, Carey D, Knight S, Meaney JF, Kenny RA, De Looze C. Relationship between hippocampal subfield volumes and cognitive decline in healthy subjects. Front Aging Neurosci. 2023;15:1284619.
  • Tarawneh R, Holtzman DM. The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb Perspect Med. 2012;2(5):a006148.
  • Yan Y, Tian M, Wang T, Wang X, Wang Y, Shi J. Transcranial magnetic stimulation effects on cognitive enhancement in mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Front Neurol. 2023;14:1209205.
  • Bashir S, Uzair M, Abualait T, et al. Effects of transcranial magnetic stimulation on neurobiological changes in Alzheimer’s disease (Review). Mol Med Rep. 2022;25(4):109.
  • Wei L, Zhang Y, Wang J, et al. Parietal-hippocampal rTMS improves cognitive function in Alzheimer’s disease and increases dynamic functional connectivity of default mode network. Psychiatry Res. 2022;315:114721.
  • Jung YH, Jang H, Park S, et al. Effectiveness of Personalized Hippocampal Network-Targeted Stimulation in Alzheimer Disease: A Randomized Clinical Trial [published correction appears in JAMA Netw Open. 2024;7(7):e2426187.
  • Velioglu HA, Hanoglu L, Bayraktaroglu Z, et al. Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer’s disease: Possible role of BDNF and oxidative stress. Neurobiol Learn Mem. 2021;180:107410.
  • DeKraker J, Haast RAM, Yousif MD, et al. Automated hippocampal unfolding for morphometry and subfield segmentation with HippUnfold. Elife. 2022;11:e77945.
  • Wang JX, Rogers LM, Gross EZ, et al. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014;345(6200):1054-7.
  • Mencarelli L, Torso M, Borghi I, et al. Macro and micro structural preservation of grey matter integrity after 24 weeks of rTMS in Alzheimer’s disease patients: a pilot study. Alzheimers Res Ther. 2024;16(1):152.
  • Suthana NA, Ekstrom AD, Moshirvaziri S, Knowlton B, Bookheimer SY. Human hippocampal CA1 involvement during allocentric encoding of spatial information. J Neurosci. 2009;29(34):10512-9.
  • Mu Y, Gage FH. Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener. 2011;6:85.
  • Kricheldorff J, Göke K, Kiebs M, et al. Evidence of Neuroplastic Changes after Transcranial Magnetic, Electric, and Deep Brain Stimulation. Brain Sci. 2022;12(7):929.
  • Jack CR Jr, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207-16.
  • Heine J, Prüß H, Scheel M, et al. Transdiagnostic hippocampal damage patterns in neuroimmunological disorders. Neuroimage Clin. 2020;28:102515.
  • Shen KK, Fripp J, Mériaudeau F, et al. Detecting global and local hippocampal shape changes in Alzheimer’s disease using statistical shape models. Neuroimage. 2012;59(3):2155-66.
There are 16 citations in total.

Details

Primary Language English
Subjects Health Services and Systems (Other)
Journal Section ORIGINAL ARTICLE
Authors

Halil Aziz Velioglu 0000-0002-2306-5937

Betül Sümbül Şekerci 0000-0001-9970-3491

Taha Hanoğlu 0000-0001-5517-4735

Ali Behram Salar 0000-0002-3691-5216

Publication Date January 29, 2025
Submission Date December 3, 2024
Acceptance Date December 28, 2024
Published in Issue Year 2025 Volume: 30 Issue: 1

Cite

Vancouver Velioglu HA, Sümbül Şekerci B, Hanoğlu T, Salar AB. The structural effects of transcranial magnetic stimulation on hippocampal subfields in Alzheimer’s disease. Anatolian Clin. 2025;30(1):62-70.

13151 This Journal licensed under a CC BY-NC (Creative Commons Attribution-NonCommercial 4.0) International License.