Prospective memory in prodromal Alzheimer's disease: Real world relevance and correlations with cortical thickness and hippocampal subfield volumes

Abstract

Introduction: Prospective memory (PM) is a marker of independent living in Alzheimer's disease. PM requires cue identification (prospective component) and remembering what should happen in response to the cue (retrospective component). We assessed neuroanatomical basis and functional relevance of PM.

Methods: 84 older participants (53-94 years old, 58% male) with or without Mild Cognitive Impairment (MCI) performed PM tests, Activities of Daily Living (ADL) scale and had a structural MRI of the brain to estimate for cortical thickness and hippocampal subfield volumes. A General Linear Model cluster analysis was carried out using FreeSurfer to determine which cortical regions were correlated with PM scores.

Results: Both components of PM are impaired in MCI (p < .001). The retrospective component of PM correlates strongly with ADL (p = .005). Prospective component performance correlates positively with cortical thickness of bilateral frontal-temporal-parietal cortex and volume of CA1 of hippocampus. In contrast, the retrospective component performance correlates positively with cortical thickness of a right-lateralised fronto-temporal-parietal network and volumes of subiculum and CA3 hippocampal subfields.

Discussion: Our neuroimaging findings complement and extend previous research into structural correlates of PM. Here, we show that there are distinct, yet, overlapping brain regions correlating with the two components of PM. PM performance provides a window into real-life functional abilities in people at risk of Alzheimer's disease and could be utilised as a marker of clinically relevant disease.

Keywords: Alzheimer's disease; Cortical thickness; Early marker; Magnetic resonance imaging; Prospective memory.

Fig. 1

Prospective Memory in three participant groups: Healthy Controls, Subjective Cognitive Decline and Mild Cognitive Impairment. Performance of the 3 groups (HC (N = 26), SCD (N = 29) and MCI (N = 29)) presented as total PM score (%). People with MCI performed significantly worse than people with SCD or HC in both the prospective component and retrospective components of Prospective Memory tasks (^⁎⁎⁎=p < .001) (N = 84). Error bars represent SD. Abbreviations: SCD, subjective cognitive decline; MCI, mild cognitive impairment.

Fig. 2

Brain maps demonstrating regions where changes in cortical thickness are significantly positively correlated with Total Prospective Memory scores. In all brain maps; top row demonstrates lateral and superior views of the brain and the bottom row represents the medial and inferior views of the brain. Total Prospective Memory left hemisphere 4 correlation clusters: middle temporal (cluster-wise p value = .0002), superior frontal (2 clusters - cluster-wise p values = .0002 and  = .0402), supramarginal (2 clusters - cluster-wise p values = .0002 and  = .0058), inferior parietal (cluster-wise p value = .0002) (N = 59). Total Prospective Memory right hemisphere 4 correlation clusters: fusiform (cluster-wise p value = .0002), superior frontal (cluster-wise p value = .0002), caudal middle frontal (cluster-wise p value = .0002) and isthmus cingulate (cluster-wise p value = .0054) (N = 59).

Fig. 3

Brain maps demonstrating regions where changes in cortical thickness are significantly positively correlated with Prospective Component and Retrospective Component scores. Prospective Component left hemisphere 7 positive correlation clusters: inferior temporal (cluster-wise p value = .0002), superior frontal (cluster-wise p value = .0002), inferior parietal (cluster-wise p value = .0002), precuneus (cluster-wise p value = .0002), supramarginal (cluster-wise p value = .0038), lateral occipital (cluster-wise p value = .0124) and superior frontal (cluster-wise p value = .0276) (N = 59). Prospective Component right hemisphere 5 positive correlation clusters: fusiform (cluster-wise p value = .0002), superior frontal (cluster-wise p value = .0002), isthmus cingulate (cluster-wise p value = .01196), superior temporal (cluster-wise p value = .0229) and caudal middle frontal (cluster-wise p value = .0441) (N = 59). Retrospective Component left hemisphere 1 positive correlation clusters: fusiform (cluster-wise p value = .02997) (N = 59). Retrospective Component right hemisphere 6 positive correlation clusters: superior temporal (cluster-wise p value = .0002), parahippocampal (cluster-wise p value = .0006), superior frontal (cluster-wise p value = .0124), medial orbitofrontal (cluster-wise p value = .0179), superior parietal (cluster-wise p value = .0181) and isthmus cingulate (cluster-wise p value = .0252) (N = 59).