AbstractBackgroundThe entorhinal cortex (EC) contains spatially modulated cells, so called grid cells, and plays a central role in spatial navigation. Studies show that tauopathy in the EC is already observed in the early stages of Alzheimer's disease (AD) and is responsible for impairments in spatial memory performance. Moreover, recent studies demonstrate that young, healthy volunteers with the APOE‐ε4‐allele, a genetic risk factor for AD, show impaired grid‐like representations in the EC and reduced path integration performance in environments without spatial cues. People with subjective cognitive decline (SCD) perceive a subjective deterioration in their cognitive memory performance with unimpaired performance on standardized neuropsychological tests. SCD corresponds to the recently defined stage 2 of AD and is also a risk factor for dementia. Here, we tested whether subjects with SCD show path integration impairment, presumably related to malfunctioning in the EC.Method68 participants (31 SCD patients recruited through a memory clinic, age: 68.8 ± 9.2; 37 controls without SCD, age: 69.1 ± 7.9) performed a path integration task on a laptop. In addition, a neuropsychological test (CERAD+) was carried out to rule out an objective cognitive impairment.ResultThe two groups did not differ in age, sex, medical history and number of educational years. We replicated previous findings indicating better path integration performance with spatial cues such as boundaries and landmarks (F(2,128) = 20.83, P < 0.001). In addition, we showed that women performed worse than men (F(1,64) = 6.00, P = 0.017) and that path integration performance declined with increasing age (F(1,64) = 32.14, P < 0.001). There was no significant difference in performance between SCD and controls (F(1,64) = 2.20, P = 0.143).ConclusionGenerally, SCD was not associated with lower path integration performance. We are in the process of characterizing the sample based on plasma amyloid beta 42/40, NFL, pTau and APOE genotype to test, if AD biomarkers and genetic risk factors are associated with path integration performance.