Abstract
Subjective memory decline is associated with neurodegeneration and increased risk of cognitive decline in participants with no or subjective cognitive impairment, while in patients with mild cognitive impairment or Alzheimer’s-type dementia, findings are inconsistent. Our aim was to provide a comprehensive overview of subjective memory decline changes, relative to objective memory performances, and of their relationships with neurodegeneration, across the clinical continuum of Alzheimer’s disease. Two hundred participants from the Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce (IMAP+) primary cohort and 731 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) replication cohort were included. They were divided into four clinical groups (Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce/Alzheimer’s Disease Neuroimaging Initiative): controls (n = 67/147, age: 60–84/60–90, female: 54/55%), patients with subjective cognitive decline (n = 30/84, age: 54–84/65–80, female: 44/63%), mild cognitive impairment (n = 50/369, age: 58–86/55–88, female: 45/44%) or Alzheimer’s-type dementia (n = 36/121, age: 51–86/61–90, female: 41/41%). Subjective and objective memory scores, and their difference (i.e. delta score reflecting memory awareness), were compared between groups. Then, voxelwise relationships between subjective memory decline and neuroimaging measures of neurodegeneration [atrophy (T1-MRI) and hypometabolism (18F-fluorodeoxyglucose-PET)] were assessed across clinical groups and the interactive effect of the level of cognitive impairment within the entire sample was assessed. Analyses were adjusted for age, sex and education, and repeated including only the amyloid-positive participants. In Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce, the level of subjective memory decline was higher in all patient groups (all P < 0.001) relative to controls, but similar between patient groups. In contrast, objective memory deficits progressively worsened from the subjective cognitive decline to the dementia group (all P < 0.001). Accordingly, the delta score showed a progressive decline in memory awareness across clinical groups (all P < 0.001). Voxelwise analyses revealed opposite relationships between the subjective memory decline score and neurodegeneration across the clinical continuum. In the earliest stages (i.e. patients with subjective cognitive decline or Mini Mental State Examination > 28), greater subjective memory decline was associated with increased neurodegeneration, while in later stages (i.e. patients with mild cognitive impairment, dementia or Mini Mental State Examination < 27) a lower score was related to more neurodegeneration. Similar findings were recovered in the Alzheimer’s Disease Neuroimaging Initiative replication cohort, with slight differences according to the clinical group, and in the amyloid-positive subsamples. Altogether, our findings suggest that the subjective memory decline score should be interpreted differently from normal cognition to dementia. Higher scores might reflect greater neurodegeneration in earliest stages, while in more advanced stages lower scores might reflect decreased memory awareness, i.e. more anosognosia associated with advanced neurodegeneration.
Highlights
Subjective cognitive decline, conceptualized as cognitive complaints, refers to the self-perception of worsening cognitive abilities relative to a previous level of performance.[1]
Amyloid SUVr was lower in IMAPþ than in Alzheimer’s Disease Neuroimaging Initiative (ADNI) for controls (P < 0.001) and SCD patients (P 1⁄4 0.01), and the MMSE score was lower in IMAPþ than in ADNI for MCI and dementia patients
Our main findings were that (i) the gap between subjective memory decline and objective memory performances increased across clinical stages, with a decrease in memory awareness at the dementia stage, which could start from the MCI stage; and (ii) the pattern of association between subjective memory decline and neurodegeneration changed across clinical groups and according to the level of cognitive impairment
Summary
Subjective cognitive decline, conceptualized as cognitive complaints, refers to the self-perception of worsening cognitive abilities relative to a previous level of performance.[1]. Such perception is often the warning signal that will motivate an individual to refer to a memory centre. Neuroimaging studies showed that SCD patients, when compared as a group to a control population, have increased levels of biomarkers suggestive of Alzheimer’s disease,[6,7] including both amyloid deposition and neurodegeneration—i.e. hippocampal atrophy and/or temporoparietal hypometabolism.[8–12]. Data suggest that SCD patients are at greater risk for Alzheimer’s disease than cognitively unimpaired elderly without subjective cognitive decline, as their subjective cognitive decline would in part reflect subtle cognitive decline that has not yet reached the level of objective impairment required for the MCI diagnosis.[13] In SCD patients, the presence of subjective cognitive decline is known to be related to an increased risk of subsequent objective cognitive decline[2,3] and conversion to dementia.[4,5] neuroimaging studies showed that SCD patients, when compared as a group to a control population, have increased levels of biomarkers suggestive of Alzheimer’s disease,[6,7] including both amyloid deposition and neurodegeneration—i.e. hippocampal atrophy and/or temporoparietal hypometabolism.[8–12] Altogether, data suggest that SCD patients are at greater risk for Alzheimer’s disease than cognitively unimpaired elderly without subjective cognitive decline, as their subjective cognitive decline would in part reflect subtle cognitive decline that has not yet reached the level of objective impairment required for the MCI diagnosis.[13]
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