Subjective spatial navigation complaints are associated with regional brain atrophy and APOE in elderly with subjective memory impairment

      Background: subjective memory complaints (SMC) may confer higher risk of developing Alzheimer’s disease (AD) known for its spatial navigation impairment. Whether subjective spatial navigation complaints (SSNC) associate with objective impairment in SMC subjects is unknown. We analyzed relationship between SSNC and brain atrophy in SMC compared to aMCI patients and controls.
      Methods: after providing consent and study approval, consecutive patients with SMC (n = 61), aMCI (n = 60) and cognitively normal elderly (CN, n = 12) were recruited from memory clinic in Prague. All had neuropsychology, 1.5 T brain scan, APOE genotyping and SSNC questionnaire inquiring about spatial skills developed in house. Brain volumes and cortical thinning were calculated using Freesurfer. Spearman correlations between SSNC and imaging measures were assesssed at alpha = .05.
      Results: SMC patients scored worse on SSNC questionnaire than CN (p = .013), whereas aMCI patients did not (p = .14). aMCI patients had more atrophy in several regions including hippocampus, entorhinal, parahippocampal and precuneus cortex compared to CN and SMC. However, in SMC, SSNC scores correlated with smaller hippocampi (rSp = -0.36, p < 0.001), while in aMCI – perhaps anosognostic to spatial difficulties - did not. SMC Ɛ4 carriers scored worse on SSNC than SMC Ɛ4 noncarriers (p = .04). SMC Ɛ4 carriers had cortical thinning in precuneus (p = .013) and parahippocampus (p = .034) compared to SMC Ɛ4 noncarriers.
      Results: Particularly SMC Ɛ4 carriers are characterized by subjective spatial navigation difficulties associated with atrophy in regions implicated in both spatial navigation and AD. Asking a specific question may be a useful screening tool for subjects at risk of AD and may guide further referral of such patients.