Brain connectivity and metacognition in persons with subjective cognitive decline (COSCODE): rationale and study design

Ribaldi, Federica; Chicherio, Christian; Altomare, Daniele; Martins, Marta; Tomczyk, Szymon; Jelescu, Ileana O.; Maturana, Enrique; Scheffler, Max; Haller, Sven; Lövblad, Karl‐Olof; Pievani, Michela; Garibotto, Valentina; Kliegel, Matthias; Frisoni, Giovanni B.

doi:10.1186/s13195-021-00846-z

Cited by 24 publications

(30 citation statements)

References 30 publications

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“…Furthermore, the risk of progression to dementia is substantially increased in case of the presence of amyloid deposition (ie, a hazard ratio of 17.0 compared with SCD with normal AD biomarkers). For these reasons, individuals with SCD are increasingly targeted in research and prevention initiatives, and are frequently included in research studies involving amyloid-PET (eg, ABIDE, AMYPAD-DPMS, DELCODE, SCIENCe, COSCODE, ALFA+). Previous studies have shown that amyloid-PET has substantial clinical consequences in terms of diagnostic change and improvement of diagnostic confidence in SCD, and many of these individuals are proactively seeking medical advice and information about their amyloid status …”

Section: Introductionmentioning

confidence: 99%

Analysis of Psychological Symptoms Following Disclosure of Amyloid–Positron Emission Tomography Imaging Results to Adults With Subjective Cognitive Decline

et al. 2023

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ImportanceIndividuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks.ObjectiveTo assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive.Design, Setting, and ParticipantsThis prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022.ExposuresDisclosure of amyloid-PET result.Main Outcomes and MeasuresPsychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale–Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms).ResultsAfter disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30]) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2]; P &lt; .001), IES-R avoidance (0.00 [0.00 to 0.69] vs 0.00 [0.00 to 0.00]; P &lt; .001), IES-R intrusions (0.50 [0.13 to 0.75] vs 0.00 [0.00 to 0.25]; P &lt; .001), and IES-R hyperarousal (0.33 [0.00 to 0.67] vs 0.00 [0.00 to 0.00]; P &lt; .001) scores than the 78 patients who were amyloid-negative (median [IQR], age, 67 [64 to 74] years, 45 men [58%], median [IQR] education: 15 [12 to 17] years, median [IQR] MMSE score: 29 [28 to 30]). There were no observed differences between amyloid-positive and amyloid-negative patients in the median (IQR) HADS Anxiety (–1.0 [–3.0 to 1.8] vs –2.0 [–4.8 to 1.0]; P = .06) and Depression (–1.0 [–2.0 to 0.0] vs –1.0 [–3.0 to 0.0]; P = .46) deltas (score after disclosure – scores at baseline). In patients with amyloid-positive SCD+, despite the small sample size, higher education was associated with lower disclosure-related distress (ρ = –0.43; P = .02) whereas the presence of study partner was associated with higher disclosure-related distress (W = 7.5; P = .03). No participants with amyloid-positive SCD+ showed probable presence of PTSD or severe anxiety or depression symptoms at follow-up.Conclusions and RelevanceThe disclosure of a positive amyloid-PET result to patients with SCD+ was associated with a bigger psychological change, yet such change did not reach the threshold for clinical concern.

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Section: Introductionmentioning

confidence: 99%

Analysis of Psychological Symptoms Following Disclosure of Amyloid–Positron Emission Tomography Imaging Results to Adults With Subjective Cognitive Decline

et al. 2023

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“…Table 1). In line with 76 , SCD was defined based on the following criteria: persons asking for help and consulting to the GMC for self-experience of deterioration in cognitive abilities, without objective cognitive impairment detected through formal neuropsychological testing. MCI was defined based on the following clinical criteria: (i) objective evidence of cognitive impairment, (ii) cognitive concern reported by the patient and/or informant (family or close friend), and (iii) little or no functional impairment in daily living activities 51 .…”

Section: Methodsmentioning

confidence: 99%

Fingerprints of brain disease: Connectome identifiability in cognitive decline and Alzheimer’s disease

Stampacchia

Asadi

Tomczyk

et al. 2022

Preprint

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In analogy to the friction ridges of a human finger, the functional connectivity patterns of the human brain can be used to identify a given individual from a population. In other words, functional connectivity patterns constitute a marker of human identity, or a brain fingerprint. Notably, very little is known about whether brain fingerprints are preserved in brain ageing and in the presence of cognitive decline. Using fMRI data of 96 memory clinic subjects, here we show that individuals functional connectivity profiles remain unique even when cognitive impairment occurs. Yet, the patterns of functional connectivity that make the healthy subjects more identifiable change during cognitive decline, suggesting that the brain undergoes functional reconfiguration. Notably, the functional connections that were the most reliable in healthy cohorts disappeared during cognitive decline, leaving room for other stable connections, adapting to the process of neurodegeneration. We believe that these findings could help in moving towards a more personalised medicine and treatment during cognitive decline, and we hope they will set the ground for clinical fingerprinting of brain disease.

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“…The individuals were classi ed as SCD if they reported cognitive complaints to the physician, without objective evidence of impairment. [19] The diagnostic workup includes clinical, neurological, and neuropsychological assessments as well as an MRI scan. Thanks to several interconnected ongoing research studies, some patients also undergo amyloid, tau PET scans, APOE genotyping, and blood-based biomarkers assessment.…”

Section: Populationmentioning

confidence: 99%

“…Thanks to several interconnected ongoing research studies, some patients also undergo amyloid, tau PET scans, APOE genotyping, and blood-based biomarkers assessment. [19] The neuropsychological battery assessed global cognition (Mini-Mental State Examination, MMSE), memory (3 objects 3 places; Free and Cued Selective Reminding Test delayed recall, FCSRT; digit span), language (category and phonemic uency), attention (Trial Making Test, TMT, A, digit symbol forward), executive functions (TMT B, TMT B-A, digit symbol backward), and visuospatial abilities (Clock). Anxiety and depression were also assessed (Hospital Anxiety and Depression Scale, HADS).…”

Section: Populationmentioning

confidence: 99%

The taxonomy of subjective cognitive decline: proposal and first clinical evidence from the Geneva memory clinic cohort

Ribaldi

Palomo

Altomare

et al. 2023

Preprint

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Background: Subjective Cognitive Decline (SCD) is characterized by subjective cognitive complaints without objective cognitive impairment and is considered a risk factor for cognitive decline and dementia. However, most SCD patients will not develop neurodegenerative disorders, yet they may suffer from minor psychiatric, neurological, or somatic comorbidities. The aim of the present study is to provide a taxonomy of the heterogeneous SCD entity by isolating homogenous SCD subgroups with specific clinical features and cognitive trajectories. Methods: Participants were fifty-five SCD individuals consecutively recruited at the Geneva Memory Center. Based on clinical reports, they were classified into three clinically pre-defined subgroups: (i) those with psychological or psychiatric comorbidities (Psy), (ii) those with somatic comorbidities (SomCom), (iii) and those with no apparent cause (NAC). Baseline demographics, clinical, cognitive, and biomarker differences among the SCD subgroups were assessed. Longitudinal cognitive changes (average 3 years follow-up) were modeled using a linear mixed model. Results: Out of the 55 SCD cases, 16 were SomCom, 18 Psy, and 21 NAC. 47% were female, mean age was 71 years. We observed higher frequency of APOE ε4 carriers in NAC (53%) compared to SomCom (14%) and Psy (0%, P=0.023) and lower level of plasma Aβ42 in NAC (6.8±1.0) compared to SomCom (8.4±1.1; P=0.031). SomCom subjects were older (74 years) than Psy (67 years, P=0.011), and had greater medial temporal lobe atrophy (1.0±1.0) than Psy (0.2±0.6) and NAC (0.4±0.5, P=0.005). SomCom have worse episodic memory performances (14.5±3.5) than Psy (15.8±0.4) and SomCom (15.1±0.7, P=0.032). We observed a slightly steeper, yet not statistically significant, cognitive decline in NAC (β=-0.48) compared to Psy (β=-0.28) and SomCom (β=-0.24). Conclusions: NAC feature higher proportion of APOE ε4 carriers, lower plasma Aβ42, worse memory performance, and a trend towards steeper cognitive decline than SomCom and Psy. Taken together, these findings suggest that NAC are at higher risk of cognitive decline due to AD. The proposed clinical taxonomy might be implemented in clinical practice to identify SCD at higher risk. However, such taxonomy should be tested on an independent cohort with larger sample size.

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Brain connectivity and metacognition in persons with subjective cognitive decline (COSCODE): rationale and study design

Cited by 24 publications

References 30 publications

Analysis of Psychological Symptoms Following Disclosure of Amyloid–Positron Emission Tomography Imaging Results to Adults With Subjective Cognitive Decline

Analysis of Psychological Symptoms Following Disclosure of Amyloid–Positron Emission Tomography Imaging Results to Adults With Subjective Cognitive Decline

Fingerprints of brain disease: Connectome identifiability in cognitive decline and Alzheimer’s disease

The taxonomy of subjective cognitive decline: proposal and first clinical evidence from the Geneva memory clinic cohort

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