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Brain connectivity and metacognition in persons with subjective cognitive decline (COSCODE): correlation with clinical features and in vivo neuropathology

English title Brain connectivity and metacognition in persons with subjective cognitive decline (COSCODE): correlation with clinical features and in vivo neuropathology
Applicant Frisoni Giovanni
Number 182772
Funding scheme Project funding (Div. I-III)
Research institution Centre de la mémoire Hôpitaux Universitaires de Genève Bâtiment Morier
Institution of higher education University of Geneva - GE
Main discipline Neurology, Psychiatry
Start/End 01.09.2019 - 31.08.2023
Approved amount 700'000.00
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Keywords (5)

Alzheimer's disease; Brain connectivity; Memory; Metacognition; MRI

Lay Summary (Italian)

I progressi nel campo della malattia di Alzheimer (AD) hanno aumentato la consapevolezza sulla salute del cervello e sulla prevenzione. Ciò porta un numero crescente di adulti a cercare aiuto nelle cliniche della memoria per dimenticanze molto lievi. Ad oggi, il 25% delle persone che afferiscono a tali cliniche lamentano un declino cognitivo in assenza di deficit oggettivi (declino cognitivo soggettivo, SCD), si prevede che tale afferenza aumenterà nei prossimi anni. L'obiettivo di COSCODE è quello di studiare l’SCD dal punto di vista clinico e patofisiologico al fine di individuare coloro a maggior rischio di sviluppare l'AD.
Lay summary

Negli ultimi anni, lo sviluppo di sofisticate tecniche di neuroimmagine ha aperto le porte alla diagnosi precoce nel campo delle demenze. Il presente progetto si rivolge a soggetti a rischio, ovvero persone con declino cognitivo soggettivo (SCD). Alcuni soggetti SCD sviluppano demenza di AD, ma la maggior parte è affetto da lievi disturbi psichiatrici, fisici, o invecchiamento cerebrale. La risonanza magnetica (RM) funzionale consente di "vedere il cervello al lavoro" e ciò potrebbe aiutare a identificare il danno di specifiche connessioni cerebrali. COSCODE ha l’obiettivo di studiare i cambiamenti di connettività cerebrale negli SCD e la loro associazione con cause neurologiche, psichiatriche e fisiche. Verranno arruolati 120 soggetti con SCD, 40 con deterioramento cognitivo lieve e 40 sani sottoposti a RM, valutazione clinica e neuropsicologica. Si eseguiranno analisi avanzate per identificare i sottogruppi di SCD con specifici pattern di connettività, caratteristiche fisiche e psichiatriche. COSCODE consentirà di individuare i soggetti con SCD in fase precoce di AD e quali siano i circuiti da utilizzare per futuri interventi riabilitativi.


Direct link to Lay Summary Last update: 03.07.2019

Lay Summary (English)

Advances in the Alzheimer’s disease (AD) field have enhanced awareness on brain health and prevention. This brings an increasing number of adults to seek help in memory clinics for very mild forgetfulness, leading to increased use of already scarce health care resources. Nowadays, about 25% of memory clinics patients complain of cognitive decline in absence of objective deficits (subjective cognitive decline, SCD), and they are expected to increase in the coming years. Some patients with SCD indeed go on to develop cognitive impairment and dementia, often due to AD, but the majority have psychiatric conditions, physical diseases, polypharmacy, or simply normal brain ageing. Differentiating these potential causes is often a difficult exercise even for expert physicians. Brain imaging with magnetic resonance allow to “see the brain at work” and might help identify the disruption of specific brain connections and identify the brain substrate of SCD.
Lay summary

This project aims to investigate brain connectivity changes in SCD and their association with neurological, psychiatric, and physical causes. Firstly, 120 SCD, 40 mild cognitive impairment and 40 healthy subjects will be enrolled and undergo clinical and neuropsychological assessments and magnetic resonance. Advanced imaging analyses will be performed to identify SCD sub-groups with patterns of connectivity changes, neurologic and psychiatric features. COSCODE will allow to discriminate SCD patients at a very early stage of AD from the others and identify circuits that might be targeted with rehabilitative or neurophysiological interventions.

Direct link to Lay Summary Last update: 03.07.2019

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BACKGROUND. Subjective cognitive decline (SCD) consists of the subjective perception of cognitive decline or impairment in the absence of objective evidence. Some SCD patients may have very early Alzheimer’s disease and others minor psychiatric conditions or physical comorbidity. However, the clinical features, natural history, taxonomy, clinical management of SCD patients are far from defined. Clinical observation leads to hypothesise that SCD patients incipient Alzheimer’s disease may have metacognitive judgements of own cognitive performance towards and overestimate, while psychiatric patients towards an underestimate. Moreover, brain connectivity changes are known correlates of AD and psychiatric conditions, and lend themselves as biomarkers to discriminate SCD patients of different aetiology. OVERARCHING AIM. COSCODE’s overarching aim will be to identify subgroups of SCD patients with coherent metacognitive, brain connectivity, psychiatric, and AD biomarker profiles. SPECIFIC AIMS. To answer the following questions: (i) Can subgroups of SCD patients be identified with coherent patterns of metacognitive judgements, connectivity changes, psychiatric features, and AD biomarkers? (ii) Are specific networks affected by connectivity changes in SCD or SCD subgroups? (iii) Can the above features separate subgroups with patient-level accuracy? (iv) What is the natural history of cognitive performance in the different SCD subgroups?DESIGN: Observational longitudinal prospective clinical cohort study. Project duration: 4 years.METHODS. Participants will be selected based on Jessen and colleagues’ definition of SCD plus, a population enriched with Alzheimer’s pre-dementia cases. Metacognition will be studied with Maniscalco and Lau’s confidence rating protocol. Diffusion and functional MRI scans will be acquired from 120 patients with SCD from the Geneva Memory Clinic; controls will be 40 patients with MCI due to AD (aka prodromal AD) and 40 healthy volunteers. SCD will be evaluated with validated questionnaires harmonised to German DELCODE, Dutch SCIENCe, and EU euroSCD and SCD-I initiatives. MR diffusion acquisitions will consist in diffusion tensor imaging at 3T in 100% of participants, and multi-shell1,2 high-angular resolution (HARDI) at 3T in 50% and at 7T in 35%. Structural connectivity analysis will be done with multi-tensor fibre tracking and graph-based modelling, and tissue microstructure analysis with multi-shell data and tissue modelling (neurite orientation dispersion and density imaging - NODDI).2,3 Functional acquisitions will include resting-state BOLD at 3T in 100% of participants and at 7T in 35%. Large-scale networks will be studied with graph-based and dynamic connectivity modelling. Participants will be phenotyped for Alzheimer’s biomarkers (genetic and imaging), psychiatric features, and physical health, and will be followed for up to 36 months to ascertain the progression of cognitive complaints to objective cognitive impairment.IMPORTANCE AND IMPACT. COSCODE will allow to: (i) define the constellation of signs and symptoms associated with different aetiologies of SCD, paving the way to the development of cost-effective diagnostic and treatment protocols; (ii) devise pharmacologic and connectivity-based interventions aimed to delay neurodegeneration and mitigate memory concerns; (iii) clarify the taxonomy of SCD and allow develop cost-effective population-based screening and clinic-based diagnostic programs.