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Advanced Neurology Neuroimaging regarding spatial navigation in AD

been extensively investigated. Therefore, spatial navigation a logistic regression model based on spatial navigation
has been considered an overlooked cognitive marker and functional connectivity measures revealed a big area
for preclinical AD . Nevertheless, spatial navigation under the curve (AUC) of 0.880 in differentiating SCD
[3]
impairments are increasingly shown to be present in individuals from NCs, indicating the promising role of
individuals with incipient AD, which may be related to spatial navigation and related neuroimaging measures in
the high susceptibility of MTL to AD pathology in the the preclinical detection of incipient AD patients.
[7]
preclinical stage . In preclinical AD subjects with genetic risk factors for
Individuals with subjective cognitive decline (SCD), AD, investigations have shown that APOE ε4 noncarriers
a self-perceived worsening of cognitive function without outperformed ε4 carriers in spatial navigation tests;
objectively detected deficits, have been widely recognized at this finding may be of use to characterize the preclinical
a higher risk of incipient AD than normal elderly individuals phase of cognitive impairment [103,104] . A recent study
without cognitive complaints [96,97] . Indeed, abundant observed significantly lower functional connectivity
evidence has suggested significant associations between between the right entorhinal cortex and PCC in subjects
amyloid pathology, genetic risk of AD, entorhinal cortical of APOE ε3ε4 group than in those of ε3ε3 group, and
thinning, and SCD [9,98] . Spatial navigation complaints are a the reduced connectivity was correlated with navigation
frequent symptom not only in patients with AD and MCI, discrepancies [105] . Therefore, the early neurodegenerative
but also in individuals with SCD. In particular, 68% of SCD processes in APOE ε4 carriers may significantly damage
subjects complained about their spatial navigation, which the neural networks that are presumed to be crucial
was significantly higher than the 33% in the NC group . for spatial navigation. Furthermore, the classification
[99]
The hidden goal task, which has been suggested to show accuracy of the path integration test, coupled with
excellent ecological validity and is strongly correlated connectivity strength between the right entorhinal cortex
with real-world navigation difficulty, was applied to and PCC, achieved an accuracy of 0.85 to distinguish
evaluate spatial navigation abilities in SCD individuals . the APOE ε4 carriers. APOE ε4 could also moderate the
[79]
In accordance with that observed in AD dementia and indirect effects of basal forebrain volumes on allocentric
MCI patients, both egocentric and allocentric navigation navigation performance through the MTL and PFC in
strategies were found to be impaired in individuals with older adults without dementia [106] . In contrast, APOE ε2 is
SCD [100,101] . Spatial navigation performance worsened known to be protective against AD and is associated with a
with increasing severity of cognitive impairment in reduced risk and delayed onset of AD [107] . Of note, Konishi
SCD, MCI, and AD dementia patients [102] . The fact that et al. found that APOE ε2 carriers tend to use allocentric
these weak levels of navigation impairment could not be spatial strategies and have greater hippocampal volumes
detected objectively using standard neuropsychological than APOE ε3 homozygous individuals and APOE ε4
evaluations of episodic memory, language, or executive carriers [108] . These findings suggest that the protective effect
functions indicates that spatial navigation is a specific of the APOE ε2 allele may be expressed in part through
cognitive domain that is impaired in the earliest stages of increased use of allocentric navigation strategies and
AD. The reduced volumes of the basal forebrain, especially greater hippocampal volumes.
in the Ch4p subfield, may serve as a structural basis for Spatial navigation impairments have also been observed
allocentric disorientation in SCD individuals independent in preclinical AD elderly individuals with abnormal AD
of hippocampal atrophy [101] . Since the Ch4p subfield biomarkers of Aβ compared to those with normal Aβ
of the basal forebrain is a key structure for cholinergic levels, suggesting that navigation may be particularly
inputs to the cerebral cortex, the results highlighted the sensitive for identifying the earliest pathologic changes in
potential role of loss of cholinergic neurons in allocentric AD [109] . Furthermore, longitudinal studies have provided
disorientation. In the rs-fMRI analyses, alterations in strong scientific evidence that spatial navigation is specific
functional connectivity between brain regions associated enough to predict conversion from normal cognition to
with spatial navigation were observed in SCD individuals. MCI or dementia [110,111] . More specifically, during an average
In particular, two spatial navigation brain networks, ego- follow-up period of 4–5 years, baseline performance on
network and allo-network, each with 10 selected spherical cognitive mapping and route learning, which depends on
regions of interest, were defined [100] . Compared with the allocentric and egocentric representation, respectively,
NCs, participants in the SCD group showed decreased were predictors of clinical progression of AD [111] .
functional connectivity between the right RSC and right The AUCs of cognitive mapping, route learning, and
prefrontal cortex (PFC) in the ego-network and decreased episodic memory for discriminating progressors from
functional connectivity between the right RSC and right nonprogressors were 0.894, 0.794, and 0.735, respectively.
hippocampus in the allo-network. More interestingly, In particular, cognitive mapping tended to perform better

Volume 1 Issue 2 (2022) 6 https://doi.org/10.36922/an.v1i2.145