Behfar, Qumars ORCID: 0000-0001-5217-924X (2025). Cognitive Stimulation Therapy in mild to moderate Alzheimer’s Disease: an MRI study. PhD thesis, Universität zu Köln.

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Abstract

This research endeavor aimed at understanding the mechanisms behind the effectiveness of Cognitive Stimulation Therapy (CST) in addressing cognitive challenges in Alzheimer's disease (AD) patients. The study, conducted at the Neurology Department of Cologne University Hospital, involved mild to moderate AD patients undergoing CST. Utilizing MRI, our goal was to uncover neural transformations underlying cognitive benefits observed in CST participants, thus advancing understanding of CST's therapeutic potential. Brain plasticity refers to the brain's ability to adapt and reorganize itself in response to experiences and injuries. This process allows for the formation of new neural connections, supporting the development of new skills and improving cognitive function. CST is designed to enhance brain plasticity and promote compensatory mechanisms in individuals with cognitive decline. Building on knowledge of neuroplasticity's role in CST and its manifestation as compensatory effects in brain imaging, our study established a framework to detect resting-state compensatory effects in healthy aging and Mild Cognitive Impairment (MCI). Using graph theory analysis of resting-state functional MRI data and volumetric analyses of structural MRI, we identified compensatory regions in the brain associated with cognitive performance. Our analysis revealed increased connectivity in certain brain regions despite atrophy, suggesting a compensatory mechanism to counter cognitive decline. These findings align with existing models of compensation in aging and neurodegeneration. Specifically, we identified regions such as the prefrontal cortex and parietal lobe showing successful compensation in MCI patients, with similarity to patterns observed in task-based compensational effect, suggesting that these regions may serve as targets for non-invasive stimulation techniques to enhance neuronal performance. With evidence of brain plasticity-driven compensation in healthy aging and MCI, our study then focused on CST's capacity to mitigate cognitive decline in mild to moderate AD, using an eight-week CST program on patients with mild to moderate AD compared to a control group with no intervention. We evaluated changes in cognition, quality of life (QoL), and brain connectivity immediately after the intervention period and at a three-month follow-up. CST was found to significantly improve cognitive function, QoL, and neuropsychiatric measures in the intervention group compared to the control group. Furthermore, our study examined the role of cognitive reserve in predicting response to CST, finding a significant correlation between improvement in cognition and years of education as a proxy measure for cognitive reserve. However, baseline total brain volume did not correlate with CST outcomes, suggesting that CST efficacy is not dependent on brain reserve in patients with mild to moderate AD. Analysis of brain connectivity using functional MRI revealed enhanced connectivity between the hippocampus and memory-related regions, suggesting neuroplastic changes induced by CST. Additionally, increased connectivity in the parietal lobes is observed, consistent with compensatory mechanisms in healthy aging and prodromal AD. Our results are suggestive of CST-induced neuronal activity, promoting compensatory neuroplasticity, particularly in regions associated with memory and self-representation. Autobiographical recall and narrative tasks incorporated into the CST program may contribute to memory enhancement and restoration of self-continuity. Finally, we discussed the potential of Maintenance Cognitive Stimulation Therapy (MCST) as a longer-term intervention to maintain cognitive gains and prevent further decline in individuals with dementia. Overall, our findings highlight the effectiveness of CST in improving cognition, QoL, and brain connectivity in patients with mild to moderate AD, and provide further evidence for the broad recommendation of CST as a cost-effective non-pharmacological treatment approach for AD and emphasizes the need for its widespread accessibility in various settings, while underscoring the importance of further research to refine intervention strategies and understand underlying mechanisms.

Item Type: Thesis (PhD thesis)
Translated title:
TitleLanguage
UNSPECIFIEDEnglish
Translated abstract:
AbstractLanguage
Ziel dieses Forschungsvorhabens war es, die Mechanismen zu verstehen, die hinter der Wirksamkeit der kognitiven Stimulationstherapie (CST) bei der Bewältigung kognitiver Herausforderungen bei Alzheimer-Patienten stehen. An der Studie, die an der Neurologischen Klinik der Uniklinik Köln durchgeführt wurde, nahmen leichte bis mittelschwere Alzheimer-Patienten teil, die sich einer CST unterzogen. Unser Ziel war es, mit Hilfe der MRT die neuronalen Veränderungen aufzudecken, die den bei den CST-Teilnehmern beobachteten kognitiven Vorteilen zugrunde liegen, und so das Verständnis für das therapeutische Potenzial der CST zu verbessern. Unter Plastizität des Gehirns versteht man die Fähigkeit des Gehirns, sich als Reaktion auf Erfahrungen und Verletzungen anzupassen und neu zu organisieren. Dieser Prozess ermöglicht die Bildung neuer neuronaler Verbindungen, die die Entwicklung neuer Fähigkeiten unterstützen und die kognitiven Funktionen verbessern. Die CST wurde entwickelt, um die Plastizität des Gehirns zu verbessern und die Kompensationsmechanismen bei Menschen mit kognitivem Abbau zu fördern. Aufbauend auf dem Wissen über die Rolle der Neuroplastizität bei der CST und ihrer Manifestation als kompensatorische Effekte in der Bildgebung des Gehirns wurde in unserer Studie ein Rahmen geschaffen, um kompensatorische Effekte im Ruhezustand bei gesundem Altern und leichter kognitiver Beeinträchtigung (MCI) zu erkennen. Mithilfe der graphentheoretischen Analyse funktioneller MRT-Daten im Ruhezustand und volumetrischer Analysen der strukturellen MRT identifizierten wir kompensatorische Regionen im Gehirn, die mit der kognitiven Leistung in Verbindung stehen. Unsere Analyse ergab, dass die Konnektivität in bestimmten Hirnregionen trotz Atrophie zunimmt, was auf einen kompensatorischen Mechanismus zum Ausgleich des kognitiven Verfalls hindeutet. Diese Ergebnisse stimmen mit bestehenden Modellen der Kompensation bei Alterung und Neurodegeneration überein. Insbesondere haben wir Regionen wie den präfrontalen Kortex und den Parietallappen identifiziert, die bei MCI-Patienten eine erfolgreiche Kompensation zeigen, mit Ähnlichkeit zu Mustern, die bei aufgabenbasierten Kompensationseffekten beobachtet wurden, was darauf hindeutet, dass diese Regionen als Ziele für nicht-invasive Stimulationstechniken zur Verbesserung der neuronalen Leistung dienen könnten. Angesichts der Belege für die Kompensation durch Hirnplastizität bei gesundem Altern und MCI konzentrierte sich unsere Studie auf die Fähigkeit der CST, den kognitiven Abbau bei leichter bis mittelschwerer Alzheimer-Krankheit abzuschwächen, indem wir ein achtwöchiges CST-Programm bei Patienten mit leichter bis mittelschwerer Alzheimer-Krankheit im Vergleich zu einer Kontrollgruppe ohne Intervention durchführten. Wir untersuchten die Veränderungen der kognitiven Fähigkeiten, der Lebensqualität und der Konnektivität des Gehirns unmittelbar nach der Intervention und nach einer dreimonatigen Nachuntersuchung. Es zeigte sich, dass die CST die kognitiven Funktionen, die Lebensqualität und die neuropsychiatrischen Messwerte in der Interventionsgruppe im Vergleich zur Kontrollgruppe deutlich verbesserte. Darüber hinaus untersuchte unsere Studie die Rolle der kognitiven Reserve bei der Vorhersage der Reaktion auf die CST und fand eine signifikante Korrelation zwischen der Verbesserung der kognitiven Fähigkeiten und den Jahren der Ausbildung als Ersatzmaß für die kognitive Reserve. Das Gesamthirnvolumen zu Beginn der Studie korrelierte jedoch nicht mit den Ergebnissen der CST, was darauf hindeutet, dass die Wirksamkeit der CST bei Patienten mit leichter bis mittelschwerer Alzheimer-Krankheit nicht von der Hirnreserve abhängt. Die Analyse der Konnektivität des Gehirns mittels funktioneller MRT ergab eine verbesserte Konnektivität zwischen dem Hippocampus und gedächtnisrelevanten Regionen, was auf neuroplastische Veränderungen durch CST hindeutet. Außerdem wurde eine erhöhte Konnektivität in den Parietallappen beobachtet, was mit kompensatorischen Mechanismen bei gesundem Altern und Alzheimer-Prodromen übereinstimmt. Unsere Ergebnisse deuten auf eine CST-induzierte neuronale Aktivität hin, die eine kompensatorische Neuroplastizität fördert, insbesondere in Regionen, die mit dem Gedächtnis und der Selbstrepräsentation verbunden sind. Autobiografische Erinnerungs- und Erzählaufgaben, die in das CST-Programm integriert sind, könnten zur Verbesserung des Gedächtnisses und zur Wiederherstellung der Selbstkontinuität beitragen. Schließlich erörterten wir das Potenzial der kognitiven Erhaltungstherapie (Maintenance Cognitive Stimulation Therapy, MCST) als längerfristige Intervention zur Aufrechterhaltung kognitiver Fortschritte und zur Verhinderung eines weiteren Rückgangs bei Menschen mit Demenz. Insgesamt unterstreichen unsere Ergebnisse die Wirksamkeit der CST bei der Verbesserung der Kognition, der Lebensqualität und der Konnektivität des Gehirns bei Patienten mit leichter bis mittelschwerer Alzheimer-Krankheit. Sie liefern weitere Belege für die breite Empfehlung der CST als kosteneffizienter nicht-pharmakologischer Behandlungsansatz bei Alzheimer-Krankheit und unterstreichen die Notwendigkeit ihrer breiten Zugänglichkeit in verschiedenen Settings.German
Creators:
CreatorsEmailORCIDORCID Put Code
Behfar, Qumarsq_behfar@yahoo.comorcid.org/0000-0001-5217-924XUNSPECIFIED
URN: urn:nbn:de:hbz:38-752175
Date: 2025
Publisher: University of Cologne
Place of Publication: Cologne, Germany
Language: English
Faculty: Faculty of Medicine
Divisions: Außeruniversitäre Forschungseinrichtungen > Forschungszentrum Jülich
Subjects: Data processing Computer science
Psychology
Natural sciences and mathematics
Medical sciences Medicine
Uncontrolled Keywords:
KeywordsLanguage
cognitive training, cognitive reserve, fMRI, plasticity, compensation, healthy aging, mild cognitive impairment, degree centrality, Brainnetome atlasEnglish
Date of oral exam: 27 January 2025
Referee:
NameAcademic Title
Özgür, A. OnurProf. Dr.
Dirk, IsbrandtProf. Dr.
Achim, TreschProf. Dr.
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Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/75217

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