Where is my hand? Proprioceptive disturbances in posterior cortical atrophy and typical Alzheimer’s disease

Abstract

AbstractBackgroundPosterior cortical atrophy (PCA) is a neurodegenerative syndrome most commonly caused by Alzheimer’s disease (AD) pathology. PCA is often considered the canonical ‘visual dementia’, characterised by the progressive loss of visual and posterior cortical functions corresponding to parieto‐occipital and occipito‐temporal atrophy. However, patient reports of difficulties finding sleeves of clothes, transferring between postures and determining heading direction imply non‐visual disturbances, consistent with the multisensory role of the posterior parietal cortex. Such reports raise questions regarding AD clinical heterogeneity, representing a substantial challenge to patients' independence and management of PCA and typical AD (tAD).MethodPatient (total n = 39; PCA n = 23; tAD n = 16) and control (n = 19) participants repeatedly reached to a proprioceptive target (their non‐dominant thumb) (Fig.A) with and without vision and tactile feedback (n = 40 trials per participant). The target was positioned passively behind a screen apparatus at five positions using an adjustable foam handrest. The primary outcome measure was absolute (medio‐lateral) error determined using whole‐body motion capture data (Fig.B).ResultAbsolute error was greater without than with vision across groups. However, the effect of removing vision on absolute error was smallest in the control group (estimated mean error with vision [95%CI]: 15mm [6,25]; without vision: 23mm [14,32]), greatest in PCA (with vision: 39mm [30,49]; without vision: 76mm [67,86]) and intermediate in the tAD group (with vision: 26mm [16,37]; without vision: 49mm [39,60]) (vision‐by‐group interaction: p<.001; Fig.C). For ∼5% of trials, absolute error exceeded 200mm in PCA and 120mm in tAD participants (Fig.B; control range: 0.01‐80mm). There was no evidence of an effect of tactile feedback in any group.The effect of target location differed between groups (location‐by‐group interaction: p<.001). Patient reaching errors were particularly apparent under postures where the target arm crossed the body midline (e.g. left arm in right hemispace); this effect was notably evident in the PCA group even with available vision (Fig.C).ConclusionFindings emphasise disturbed spatial awareness in PCA and tAD in the absence of vision, consistent with diminished body position sense‐ proprioception ‐ which may be mediated centrally through posterior parietal vulnerability. Findings suggest implications for assessment and management of disabling dressing, mobility, navigation and balance difficulties.