U n c o r r e c t e d A u t h o r P r o o fJournal of Alzheimer's Disease xx (20xx) x-xx Abstract. Spatial navigation tasks reveal small differences between normal and pathological aging and may thus disclose potential neuropsychological predictors of neurodegenerative diseases. The aim of our study was to investigate which navigational skills are compromised in the early phase of pathological aging as well as the extent to which they are compromised. We performed an extensive neuropsychological evaluation based on working memory and learning tasks (i.e., Corsi Block-Tapping Test and Walking Corsi Test) involving both reaching and navigational vista spaces. We also assessed spatial navigation skills in the real world by asking participants to perform route-learning and landmark-recognition tasks. We conducted a cross-sectional study on nineteen patients with a diagnosis of mild cognitive impairment (MCI) who displayed either an isolated memory deficit (single-domain amnestic MCI, MCIsd; N = 3) or a memory deficit associated with deficits in other cognitive functions (multi-domain MCI, MCImd; N = 16) as well as on nineteen healthy control participants. The groups' performances were compared by means of mixed factorial ANOVA and two-sample t-tests. We found that patients with MCI performed worse than controls, especially when they were required to learn spatial positions within the navigational vista space. Route-learning within the real environment was also impaired whereas landmark-recognition was spared. The same pattern of results emerged in the MCImd subgroup. Moreover, single case analyses on MCIsd patients revealed a dissociation between learning of spatial positions within navigational vista space and within reaching space. These results suggest that topographical learning is compromised in the early phase of MCIsd and MCImd and that spatial navigation tasks may be used to better characterize topographical disorientation in MCI patients as well as for the early diagnosis of pathological aging.

Neuropsychological studies on acquired topographical disorientation have provided useful insights into the contribution of different brain regions to human navigation. However, little is known about the possibility to restore navigational skills after brain damage. Here we describe the case of No Longer Lost (NLL), a 49-year-old man who complained of severe topographical disorientation following traumatic brain injury. Extensive neuropsychological evaluation at baseline revealed selective episodic memory deficits and topographical disorientation. NLL underwent 8-week imagery-based treatment (IBT) inspired by current cognitive models of human spatial navigation. After IBT, NLL improved topographical skills and episodic memory. From a clinical point of view, the present study describes a model-based intervention for topographical disorientation. From a theoretical point of view, it provides new insights into the cognitive models of human spatial navigation and straightforward evidence about common phylogenetic roots of brain mechanisms devoted to spatial navigation and memory.

This study aimed to explore the prevalence and safety of SARS-CoV-2 vaccination in individuals with dementia. Patients with mild cognitive impairment or dementia were recruited at a tertiary memory clinic, from March 15 to September 15, 2021. Information on COVID-19 vaccination and adverse events experienced after vaccine administration were collected from caregivers. Two-hundred-seventy subjects were finally recruited. Among them, 253 (93.7%) had received the vaccine and only 69 (27.3%) experienced adverse events. Cognitive and behavioral changes following immunization were only rarely reported. COVID-19 vaccination is safe and well-tolerated in patients with cognitive impairment who should be prioritized in the vaccination campaign.