Journal of Istanbul Faculty of Medicine

SUBMITINFORMATION
EnglishTürkçe

Research Article


DOI :10.26650/IUITFD.1581821   IUP :10.26650/IUITFD.1581821    Full Text (PDF)

CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE

Gözde Kızılateş Evin, Ali Bayram, Elif Kurt, Emre Harı, Çiğdem Ulaşoğlu Yıldız, İbrahim Hakan Gürvit, Tamer Demiralp

Objective: Alzheimer’s Progressive Memory Impairment Contin uum (PMIC) is typically the clinical reflection of the neurofibrillary tangle (NFT) spread of Alzheimer’s disease (AD), which starts with subtle memory complaints of subjective cognitive impairment (SCI), passes through objectifiable memory problems of the am nestic mild cognitive impairment (aMCI), and finally reaches the dementia stage of multiple cognitive deficits with an amnestic core (ADD). This study evaluated the patterns of cortical thick ness changes across the PMIC, using a network perspective to unravel structural and functional disruptions.

Material and Methods: The study included 88 participants: 21 with mild ADD, 34 with aMCI, and 33 with SCI. Clinical and neu ropsychiatric evaluations were conducted, followed by structural MRI scanning for cortical thickness measurements. Vertex-wise cortical thickness analyses were conducted using ANCOVA. Age, gender, and education were covariates.

Result: The results showed significant cortical thinning across the PMIC, with more pronounced reductions in the ADD group. The cortical thinning overlapped with the Default Mode Net work (DMN), Ventral Attention Network (VAN), and Frontoparietal Network (FPN). The comparison between the SCI and aMCI groups revealed no significant difference.

Conclusion: Cortical thinning was evident across different stages of PMIC, with more extensive thinning in later stages. The observed network-wide pattern of atrophy that AD-like deterioration affects broader neural systems rather than isolated regions. The findings highlight the importance of a network based approach to understand AD-related structural changes and the potential for future research to integrate multimodal imaging to explore functional connectivity alongside structural atrophy.

Keywords: Alzheimer’s disease, mild cognitive impairment, structural magnetic resonance imaging, cortical thickness
DOI :10.26650/IUITFD.1581821   IUP :10.26650/IUITFD.1581821    Full Text (PDF)

ALZHEIMER'İN İLERLEYİCİ BELLEK BOZUKLUĞU SÜREKLİLİĞİNDE KORTİKAL KALINLIK DEĞİŞİMLERİ: AĞ PERSPEKTİFİ

Gözde Kızılateş Evin, Ali Bayram, Elif Kurt, Emre Harı, Çiğdem Ulaşoğlu Yıldız, İbrahim Hakan Gürvit, Tamer Demiralp

Amaç: Alzheimer'ın İlerleyici Bellek Bozukluğu Sürekliliği (İBBS), Alzheimer hastalığında (AH) nörofibriler yumak (NFY) yayılımının klinik yansımasıdır. Bu süreç, subjektif kognitif bozukluk (SKB) olarak bilinen hafif bellek şikayetleriyle başlayıp, amnestik hafif kognitif bozukluk (aHKB) olarak adlandırılan belirginleşmiş bel lek problemlerine, nihayetinde amnestik bir çekirdekle karakte rize edilen çoklu kognitif bozuklukları içeren demans aşamasına (AHD) ulaşır. Bu çalışma, İBBS boyunca kortikal kalınlık değişim paternlerini ağ perspektifiyle değerlendirerek yapısal ve fonksi yonel bozulmaları ortaya çıkarmayı amaçlamıştır.

Gereç ve Yöntem: Bu çalışmaya, 21 hafif AHD, 34 aHKB ve 33 SKB olmak üzere 88 katılımcı dahil edilmiştir. Klinik ve nöropsiki yatrik değerlendirmeler yapıldıktan sonra, kortikal kalınlık ölçüm leri için yapısal MRG taraması gerçekleştirilmiştir. Verteks-temelli kortikal kalınlık analizleri ANCOVA kullanılarak yapılmıştır. Yaş, cinsiyet ve eğitim kovaryet değişkenlerdi.

Bulgular: Sonuçlar, İBBS boyunca anlamlı kortikal incelme old uğunu ve bu incelmenin AHD grubunda daha belirgin olduğunu göstermiştir. Kortikal incelme Olağan Durum Ağı (ODA), Ventral Dikkat Ağı (VDA) ve Frontoparyetal Ağ (FPA) ile örtüşmektedir. SKB ve aHKB grupları arasındaki karşılaştırmada anlamlı bir fark bulunamamıştır.

Sonuç: Kortikal incelme, IBBS'nin farklı evrelerinde belirgindir ve özellikle ileri evrelerde daha yaygın görülmektedir. Ağ genelinde gözlemlenen atrofi paterni, AH-benzeri bozulmanın yalnızca izo le bölgeleri değil, daha geniş sinir sistemlerini etkilediğini gös termektedir. Bulgular, AH ile ilişkili yapısal değişiklikleri anlamak için ağ tabanlı bir yaklaşımın önemini vurgulamakta ve yapısal atrofinin yanı sıra fonksiyonel bağlantısallığı keşfetmek için ge lecekteki araştırmalara çoklu modalite görüntülemeyi entegre etme potansiyeline dikkat çekmektedir.

Keywords: Alzheimer hastalığı, hafif kognitif bozukluk, yapısal manyetik rezonans görüntüleme, kortikal kalınlık

PDF View

References

  • Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol 2010;9(1):119-28. [CrossRef] google scholar
  • Braak H, Braak E. Neuropathological stageing of Alzheimerrelated changes. Acta Neuropathol 1991;82(4):239-59. [CrossRef] google scholar
  • Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011;70(11):960-9. [CrossRef] google scholar
  • Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7(3):280-92. [CrossRef] google scholar
  • Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256(3):183-94. [CrossRef] google scholar
  • Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001;58(12):1985-92. [CrossRef] google scholar
  • Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, et al. Mild cognitive impairment-- beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256(3):240-6. [CrossRef] google scholar
  • Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, et al. Conversion of mild cognitive impairment to dementia: predictive role of mild cognitive impairment subtypes and vascular risk factors. Dement Geriatr Cogn Disord 2006;21(1):51-8. [CrossRef] google scholar
  • Rabin LA, Smart CM, Amariglio RE. Subjective cognitive decline in preclinical Alzheimer’s disease. Annu Rev Clin Psychol 2017;13(1):369-96. [CrossRef] google scholar
  • Jessen F, Amariglio RE, Van Boxtel M, Breteler M, Ceccaldi M, Chételat G, et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement 2014;10(6):844-52. [CrossRef] google scholar
  • Petersen RC, Lopez O, Armstrong MJ, Getchius TS, Ganguli M, Gloss D, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2018;90(3):126-35. [CrossRef] google scholar
  • Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7(3):270-9. [CrossRef] google scholar
  • Hari E, Kurt E, Ulasoglu-Yildiz C, Bayram A, Bilgic B, Demiralp T, et al. Morphometric analysis of medial temporal lobe subregions in Alzheimer’s disease using high-resolution MRI. Brain Struct Funct 2023;228(8):1885-99. [CrossRef] google scholar
  • Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN, et al. The cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex 2009;19(3):497-510. [CrossRef] google scholar
  • Desikan RS, Cabral HJ, Hess CP, Dillon WP, Glastonbury CM, Weiner MW, et al. Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer’s disease. Brain 2009;132(8):2048-57. [CrossRef] google scholar
  • Sheline YI, Morris JC, Snyder AZ, Price JL, Yan Z, D’Angelo G, et al. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Abeta42. J Neurosci 2010;30(50):17035-40. [CrossRef] google scholar
  • Sheline YI, Raichle ME, Snyder AZ, Morris JC, Head D, Wang S, et al. Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry 2010;67(6):584-7. [CrossRef] google scholar
  • Pievani M, de Haan W, Wu T, Seeley WW, Frisoni GB. Functional network disruption in the degenerative dementias. Lancet Neurol 2011;10(9):829-43. [CrossRef] google scholar
  • Buschke H. Cued recall in amnesia. J Clin Exp Neuropsychol 1984;6(4):433-40. [CrossRef] google scholar
  • Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12(3):189-98. [CrossRef] google scholar
  • Ivnik RJ, Smith GE, Lucas JA, Tangalos EG, Kokmen E, Petersen RC. Free and cued selective reminding test: MOANS norms. J Clin Exp Neuropsychol 1997;19(5):676- 91. [CrossRef] google scholar
  • Morris JC. The Clinical Dementia Rating (CDR) current version and scoring rules. Neurology 1993;43(11):2412-4. [CrossRef] google scholar
  • McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7(3):263-9. [CrossRef] google scholar
  • Grober E, Sanders AE, Hall C, Lipton RB. Free and cued selective reminding identifies very mild dementia in primary care. Alzheimer Dis Assoc Disord 2010;24(3):284- 90. [CrossRef] google scholar
  • Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256(3):183-94. [CrossRef] google scholar
  • Jessen F, Wolfsgruber S, Wiese B, Bickel H, Mösch E, Kaduszkiewicz H, et al. AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement 2014;10(1):76-83. [CrossRef] google scholar
  • Dahnke R, Yotter RA, Gaser C. Cortical thickness and central surface estimation. Neuroimage 2013;65:336-48. [CrossRef] google scholar
  • Ashburner J, Friston KJ. Unified segmentation. Neuroimage 2005;26(3):839-51. [CrossRef] google scholar
  • Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage 2007;38(1):95-113. [CrossRef] google scholar
  • Yotter RA, Dahnke R, Thompson PM, Gaser C. Topological correction of brain surface meshes using spherical harmonics. Hum Brain Mapp 2011;32(7):1109-24. [CrossRef] google scholar
  • Yotter RA, Thompson PM, Gaser C. Algorithms to improve the reparameterization of spherical mappings of brain surface meshes. J Neuroimaging 2011;21(2): e134-e147. [CrossRef] google scholar
  • Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 2011;106(3):1125-65. [CrossRef] google scholar
  • Vogt NM, Hunt JF, Adluru N, Dean DC III, Johnson SC, Asthana S, et al. Cortical microstructural alterations in mild cognitive impairment and Alzheimer’s disease dementia. Cereb Cortex 2020;30(5):2948-60. [CrossRef] google scholar
  • Montal V, Vilaplana E, Alcolea D, Pegueroles J, Pasternak O, González‐Ortiz S, et al. Cortical microstructural changes along the Alzheimer’s disease continuum. Alzheimers Dement 2018;14(3):340-51. [CrossRef] google scholar
  • Bakkour A, Morris JC, Dickerson BC. The cortical signature of prodromal AD: regional thinning predicts mild AD dementia. Neurology 2009;72(12):1048-55. [CrossRef] google scholar
  • Ferreira LK, Busatto GF. Resting-state functional connectivity in normal brain aging. Neurosci Biobehav Rev 2013;37(3):384-400. [CrossRef] google scholar
  • Ferreira LK, Busatto GF. Neuroimaging in Alzheimer’s disease: current role in clinical practice and potential future applications. Clinics 2011;66:19-24. [CrossRef] google scholar
  • Mevel K, Chételat G, Eustache F, Desgranges B. The default mode network in healthy aging and Alzheimer’s disease. Int J Alzheimers Dis 2011;2011:535816. [CrossRef] google scholar
  • Buckner RL, Andrews‐Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008;1124(1):1-38. [CrossRef] google scholar
  • Greicius MD, Srivastava G, Reiss AL, Menon V. Defaultmode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI. Proc Natl Acad Sci USA 2004;101(13):4637-42. [CrossRef] google scholar
  • Villemagne VL, Pike KE, Chetelat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol 2011;69(1):181-92. [CrossRef] google scholar
  • Onoda K, Ishihara M, Yamaguchi S. Decreased functional connectivity by aging is associated with cognitive decline. J Cogn Neurosci 2012;24(11):2186-98. [CrossRef] google scholar
  • Brier MR, Thomas JB, Snyder AZ, Benzinger TL, Zhang D, Raichle ME, et al. Loss of intranetwork and internetwork resting state functional connections with Alzheimer’s disease progression. J Neurosci 2012;32(26):8890-9. [CrossRef] google scholar
  • Nabizadeh F. Disruption in functional networks mediated tau spreading in Alzheimer’s disease. Brain Commun 2024;6(4):fcae198. [CrossRef] google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Kızılateş Evin, G., Bayram, A., Kurt, E., Harı, E., Ulaşoğlu Yıldız, Ç., Gürvit, İ.H., & Demiralp, T. (2025). CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE. Journal of Istanbul Faculty of Medicine, 88(2), 90-97. https://doi.org/10.26650/IUITFD.1581821


AMA

Kızılateş Evin G, Bayram A, Kurt E, Harı E, Ulaşoğlu Yıldız Ç, Gürvit İ H, Demiralp T. CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE. Journal of Istanbul Faculty of Medicine. 2025;88(2):90-97. https://doi.org/10.26650/IUITFD.1581821


ABNT

Kızılateş Evin, G.; Bayram, A.; Kurt, E.; Harı, E.; Ulaşoğlu Yıldız, Ç.; Gürvit, İ.H.; Demiralp, T. CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 88, n. 2, p. 90-97, 2025.


Chicago: Author-Date Style

Kızılateş Evin, Gözde, and Ali Bayram and Elif Kurt and Emre Harı and Çiğdem Ulaşoğlu Yıldız and İbrahim Hakan Gürvit and Tamer Demiralp. 2025. “CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE.” Journal of Istanbul Faculty of Medicine 88, no. 2: 90-97. https://doi.org/10.26650/IUITFD.1581821


Chicago: Humanities Style

Kızılateş Evin, Gözde, and Ali Bayram and Elif Kurt and Emre Harı and Çiğdem Ulaşoğlu Yıldız and İbrahim Hakan Gürvit and Tamer Demiralp. “CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE.” Journal of Istanbul Faculty of Medicine 88, no. 2 (May. 2025): 90-97. https://doi.org/10.26650/IUITFD.1581821


Harvard: Australian Style

Kızılateş Evin, G & Bayram, A & Kurt, E & Harı, E & Ulaşoğlu Yıldız, Ç & Gürvit, İH & Demiralp, T 2025, 'CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE', Journal of Istanbul Faculty of Medicine, vol. 88, no. 2, pp. 90-97, viewed 8 May. 2025, https://doi.org/10.26650/IUITFD.1581821


Harvard: Author-Date Style

Kızılateş Evin, G. and Bayram, A. and Kurt, E. and Harı, E. and Ulaşoğlu Yıldız, Ç. and Gürvit, İ.H. and Demiralp, T. (2025) ‘CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE’, Journal of Istanbul Faculty of Medicine, 88(2), pp. 90-97. https://doi.org/10.26650/IUITFD.1581821 (8 May. 2025).


MLA

Kızılateş Evin, Gözde, and Ali Bayram and Elif Kurt and Emre Harı and Çiğdem Ulaşoğlu Yıldız and İbrahim Hakan Gürvit and Tamer Demiralp. “CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE.” Journal of Istanbul Faculty of Medicine, vol. 88, no. 2, 2025, pp. 90-97. [Database Container], https://doi.org/10.26650/IUITFD.1581821


Vancouver

Kızılateş Evin G, Bayram A, Kurt E, Harı E, Ulaşoğlu Yıldız Ç, Gürvit İH, Demiralp T. CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE. Journal of Istanbul Faculty of Medicine [Internet]. 8 May. 2025 [cited 8 May. 2025];88(2):90-97. Available from: https://doi.org/10.26650/IUITFD.1581821 doi: 10.26650/IUITFD.1581821


ISNAD

Kızılateş Evin, Gözde - Bayram, Ali - Kurt, Elif - Harı, Emre - Ulaşoğlu Yıldız, Çiğdem - Gürvit, İbrahimHakan - Demiralp, Tamer. “CORTICAL THICKNESS ALTERATIONS IN ALZHEIMER’S PROGRESSIVE MEMORY IMPAIRMENT CONTINUUM: A NETWORK PERSPECTIVE”. Journal of Istanbul Faculty of Medicine 88/2 (May. 2025): 90-97. https://doi.org/10.26650/IUITFD.1581821



TIMELINE


Submitted09.11.2024
Accepted03.12.2024
Published Online13.03.2025

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE



Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.