Evaluation of APOE ɛ2/ɛ3/ɛ4 Alleles in a Cohort of Individuals Affected by Developmental Topographical Disorientation

The three common alleles of the APOE gene, ɛ2/ɛ3/ɛ4, have been linked to human spatial orientation. We investigated the genetic role of APOE in developmental topographical disorientation (DTD), a lifelong condition that results in topographical disorientation. We genotyped the APOE ɛ2/ɛ3/ɛ4 alleles in a cohort of 20 unrelated DTD probands, and found allele frequencies not statistically different from the those seen in the population as a whole. Therefore, we found no evidence that DTD occurs preferentially on a genetic background containing any particular APOE allele, making it unlikely that these APOE alleles are contributing to the development of DTD.

Developmental Topographical Disorientation With Concurrent Face Recognition Deficit: A Case Report

Developmental topographical disorientation (DTD) has been defined as a developmental deficit in human navigational skills in the absence of congenital or acquired brain damage. We report the case of Lost In Space Again (LISA), a 22-year-old woman with a normal development and no clinical history of neurological or psychiatric diseases, evaluated twice, with an interval of 5 years. The magnetic resonance imaging (MRI) examination did not reveal any morphological alteration, while diffusion tensor imaging (DTI) showed a structural connectivity deficit (a decreased fractional anisotropy—FA) in the parieto–prefrontal and parieto–premotor pathway. The behavioral assessment showed different deficits in spatial and navigational tasks, which seemed to be connected to a poor ability to form a cognitive map of the environment. Moreover, LISA displayed a poor performance in high-level face encoding and retrieval. The aim of this case report is to share new insight about DTD in order to deepen the knowledge of this specific neurodevelopmental disorder. In conclusion, this novel DTD case (1) supports the hypothesis of the existence of different DTD subtypes; (2) sustains the evidence that DTD can co-occur (or not) with deficit in face recognition; and (3) highlights the need for an in-depth examination from both a neurocognitive and behavioral point of view of a possible common developmental defect between the formation of cognitive maps and the recognition of faces that might be in mental imagery skills. Future directions will be also discussed.

Behavioural and cognitive mechanisms of Developmental Topographical Disorientation

Individuals affected by Developmental Topographical Disorientation (DTD) get lost on a daily basis, even in the most familiar of surroundings such as their neighbourhood, the building where they have worked for many years, and, in extreme cases, even in their own homes. Individuals with DTD report a lifelong selective inability to orient despite otherwise well-preserved general cognitive functions, and the absence of any acquired brain injury or neurological condition, with general intelligence reported to be within the normal range. To date, the mechanisms underlying such a selective developmental condition remain unknown. Here, we report the findings of a 10-year-long study investigating the behavioural and cognitive mechanisms of DTD in a large sample of 1211 cases. We describe the demographics, heritability pattern, self-reported and objective spatial abilities, and some personality traits of individuals with DTD as compared to a sample of 1624 healthy controls; importantly, we test the specific hypothesis that the presence of DTD is significantly related to the inability of the individuals to form a mental representation of the spatial surroundings (i.e., a cognitive map). We found that individuals with DTD reported relatively greater levels of neuroticism and negative affect, and rated themselves more poorly on self-report measures of memory and imagery skills related to objects, faces, and places. While performing interactive tasks, as a group, the individuals with DTD performed slightly worse on a scene-based perspective-taking task, and, notably struggled to solve tasks that demand the generation and use of a cognitive map. These novel findings help define the phenotype of DTD, and lay the foundation for future studies of the neurological and genetic mechanisms of this lifelong condition.

Egocentric and Allocentric Spatial Cognition in Amnestic Mild Cognitive Impairment and Early Alzheimer’s Disease

Background: Topographical disorientation is one of the early symptoms of Alzheimer’s disease (AD). The nature of this symptom, however, remains unclear. Objective: The aim of the study was to investigate egocentric and allocentric spatial cognition in patients with amnestic mild cognitive impairment (aMCI) and early AD. Participants and Methods: The participants consisted of normal healthy volunteers (n = 23), patients with aMCI (n = 26), and patients with early AD (n = 22). We administered the card placing test (CPT), in which a subject was required to recreate an array of 3 cards, each of which was randomly placed on 8 grids around the individual, before (part A) and after (part B) the individual’s rotation. With this design, the CPT can reveal an individual’s ability to represent spatial information either egocentrically (CPT-A) or allocentrically (CPT-B). A qualitative analysis of errors in performing the CPT was also conducted. Results: Compared with the controls, the aMCI patients showed significantly poorer CPT-B performance, while there was no significant difference in CPT-A performance between these 2 groups. In contrast, the AD patients demonstrated significantly poorer performance on both the CPT-A and CPT-B than the controls and aMCI patients. There was no significant difference in the profile of errors on the CPT-B between the controls and aMCI patients, whereas there was a notable difference in those on the CPT-A between the controls and AD patients and the aMCI and AD patients. Conclusion: Allocentric spatial cognition is selectively impaired in aMCI patients, while an egocentric spatial cognition is additionally impaired in AD patients.