BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.
- MeSH
 - Alzheimer Disease * genetics cerebrospinal fluid diagnostic imaging complications physiopathology pathology MeSH
 - Amyloid beta-Peptides cerebrospinal fluid MeSH
 - Apolipoprotein E4 * genetics MeSH
 - Apolipoproteins E * genetics MeSH
 - Atrophy MeSH
 - Biomarkers cerebrospinal fluid MeSH
 - Genotype MeSH
 - Cognitive Dysfunction * genetics cerebrospinal fluid diagnostic imaging physiopathology MeSH
 - Middle Aged MeSH
 - Humans MeSH
 - Magnetic Resonance Imaging MeSH
 - Brain pathology diagnostic imaging MeSH
 - Neuropsychological Tests MeSH
 - Peptide Fragments cerebrospinal fluid MeSH
 - Positron-Emission Tomography MeSH
 - Spatial Navigation * physiology MeSH
 - tau Proteins cerebrospinal fluid MeSH
 - Aged, 80 and over MeSH
 - Aged MeSH
 - Check Tag
 - Middle Aged MeSH
 - Humans MeSH
 - Male MeSH
 - Aged, 80 and over MeSH
 - Aged MeSH
 - Female MeSH
 - Publication type
 - Journal Article MeSH