Association of the Informant-Reported Memory Decline With Cognitive and Brain Deterioration Through the Alzheimer Clinical Continuum

Abstract

<h3>Background and objectives:</h3> Studies are sparse regarding the association between the informant-reported subjective memory decline (informant-report) and Alzheimer’s disease (AD) biomarkers. This study thus aimed at determining the clinical relevance of the informant-report throughout the AD clinical continuum, by assessing its specific relationships with amyloid deposition, cognition and neurodegeneration. <h3>Methods:</h3> Participants from the <i>Imagerie Multimodale de la maladie d9Alzheimer à un stade Précoce</i> (IMAP+) primary cohort and from the <i>Alzheimer’s Disease Neuroimaging Initiative</i> (ADNI) replication cohort were included; all underwent multimodal neuroimaging and neuropsychological assessments. Follow-up data of IMAP+ participants over up to 36 months were also used for longitudinal analyses. The informant-report was measured respectively with the Cognitive Difficulties Scale (IMAP+) and Everyday Cognition (ADNI). General linear models were used to assess the cross-sectional associations between the informant-report and amyloid-PET, cognitive performances, and neurodegeneration (atrophy and hypometabolism) in Alzheimer’s-signature areas; while longitudinal links were assessed in IMAP+ with linear mixed-effects models. <h3>Results:</h3> 110 IMAP+ participants were included, including 32 cognitively unimpaired elders (controls, age: 70.91±6.57, female:50%), 25 patients with subjective cognitive decline (SCD, 65.88±6.64, 40%), 35 with mild cognitive impairment (MCI, 72.49±7.5, 34%) and 18 with Alzheimer’s-type dementia (AD dementia, 68.17±8.59, 28%). 731 ADNI participants were included, including 157 controls (74.21±5.95, 55%), 84 SCD (72.00±5.41, 63%), 369 MCI (71.84±7.4, 44%) and 121 AD dementia (74.29±7.75, 40%). In IMAP+, higher informant-report strongly correlated to greater amyloid-PET specifically in MCI patients (β=0.48, p=.003), and to lower cognitive performance in SCD (global cognition, β=-0.41, p=.04) and MCI patients (memory, β=-0.37, p=.03). Findings in MCI patients were replicated in ADNI (amyloid-PET, β=0.25, p&lt;.001; memory, β=-0.22, p&lt;.001), and extended to neurodegeneration in AD signature areas (β=-0.2, p&lt;.001). Longitudinal analyses in IMAP+ showed links with global cognitive decline over time in MCI (est. -0.74, SE 0.26, p=.005) and in SCD (est. -0.36, SE 0.26, p=.02) patients where higher baseline informant-report also predicted increased amyloid-PET over time (est. 0.008, SE 0.003, p=.02). <h3>Discussion:</h3> Altogether, our findings suggest that the informant-report is particularly relevant in MCI patients where it strongly relates to higher amyloid-PET, indicative of impairment due-to-AD. <h3>Trial registration information:</h3> ClinicalTrials.gov Identifier: NCT01638949

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