The effect of TOMM40 on spatial navigation in amnestic mild cognitive impairment

Spatial navigation and risk of cognitive impairment: A prospective cohort study

“…[30] Specific gene variants such as APOE and TOMM40 genotypes that are associated with increased risk of developing AD were reported to influence exocentric but not egocentric navigation in older adults with amnestic MCI. [31, 32] Neuroimaging studies indicate that exocentric navigation relies on hippocampal and parietal regions,[3, 33, 34] which are known to be vulnerable to Alzheimer pathology. On the other hand, FMT did not predict incidence of amnestic MCI or memory decline in our sample.…”

The Aging Navigational System

“…Impaired grid cell-like properties have also been reported in young adults who were carriers of the APOE E4 allele (Kunz et al, 2015), suggesting that physiological changes in grid cell networks may appear very early in adulthood (Figure 5). In addition to the APOE E4 gene, a negative influence of other genetic risk factors for AD on navigation skill has been observed among carriers of the VL variant of the Tomm40 gene (Laczó et al, 2015) and the T polymorphism of the KIBRA gene (Schuck et al, 2013). Given that old, memory-deficient rats show improved memory following pharmacological treatments that manipulate KIBRA activity (Huentelman et al, 2009), KIBRA pathways may be promising therapeutic targets for cognitive enhancement in normative aging, and potentially in attenuating AD-related memory deficits.…”

Normal Aging and Dementia

“…The volunteers underwent neuropsychological testing every 2 years. This study [55] showed that the influence of TOMM40 variation on memory decline was particularly visible in subjects before 60 years of age (p = 0.009), however only in TOMM40 VL/VL carriers whose improvement after the test-retest was significantly less pronounced than in the S/S and S/VL carriers. Moreover, the authors performed a neuropsychological examination and testing using the human analog of the Morris water maze and brain MRI on 59 cognitively normal volunteers, stratified as S/S, S/VL, and VL/VL carriers.…”

“…They also found that the TOMM40 variants significantly influenced the brain structure. The S/S group had a thicker right entorhinal cortex (p ≤ 0.043) than the S/VL and VL/VL groups, whereas significant thinning of the left entorhinal cortex and the left posterior cingulate cortex was present only in the VL/VL group (p = 0.043 and p = 0.024, respectively) as compared to the S/S group [55]. In another interesting study [56], the authors stratified 117 healthy adults (medium age: 55 years) with the APOE E3/E3 genotype according to the TOMM40 status into three groups, S/S, S/VL, and VL/VL, and performed memory tests and structural brain imaging.…”

“…Moreover, they observed that the S variant significantly reduced vocabulary ability, diminished age-dependent vocabulary decline, in subjects as compared to the VL variant carriers. Other authors [55] conducted longitudinal modeling of a cognitive aging study on a cohort of 639 subjects with no signs of dementia, aged 21 to 97 years with a known TOMM40 and APOE status. The volunteers underwent neuropsychological testing every 2 years.…”