Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus-dependent) and egocentric (body-centered, parietal lobe dependent) navigation and learning in young vs. older adults, and to assess a possible influence of gender. We recruited healthy participants without cognitive deficits on standard neuropsychological testing, white matter lesions or pronounced hippocampal atrophy: 24 young participants (18-26 years old) and 44 older participants stratified as participants 60-70 years old (n = 24) and participants 71-84 years old (n = 20). All underwent spatial navigation testing in the real-space human analog of the Morris Water Maze, which has the advantage of assessing separately allocentric and egocentric navigation and learning. Of the eight consecutive trials, trials 2-8 were used to reduce bias by a rebound effect (more dramatic changes in performance between trials 1 and 2 relative to subsequent trials). The participants who were 71-84 years old (p < 0.001), but not those 60-70 years old, showed deficits in allocentric navigation compared to the young participants. There were no differences in egocentric navigation. All three groups showed spatial learning effect (p' s ≤ 0.01). There were no gender differences in spatial navigation and learning. Linear regression limited to older participants showed linear (β = 0.30, p = 0.045) and quadratic (β = 0.30, p = 0.046) effect of age on allocentric navigation. There was no effect of age on egocentric navigation. These results demonstrate that navigation deficits in older age may be limited to allocentric navigation, whereas egocentric navigation and learning may remain preserved. This specific pattern of spatial navigation impairment may help differentiate normal aging from prodromal Alzheimer's disease.

• Keywords
• Alzheimer’s disease, aging, allocentric navigation, egocentric navigation, gender, hippocampus, spatial learning, spatial navigation,
• Publication type
• Journal Article MeSH

Individuals with subjective cognitive decline (SCD) are at higher risk of incipient Alzheimer's disease (AD). Spatial navigation (SN) impairments in AD dementia and mild cognitive impairment patients have been well-documented; however, studies investigating SN deficits in SCD subjects are still lacking. This study aimed to explore whether basal forebrain (BF) and entorhinal cortex (EC) atrophy contribute to spatial disorientation in the SCD stage. In total, 31 SCD subjects and 24 normal controls were enrolled and administered cognitive scales, a 2-dimensional computerized SN test, and structural magnetic resonance imaging (MRI) scanning. We computed the differences in navigation distance errors and volumes of BF subfields, EC, and hippocampus between the SCD and control groups. The correlations between MRI volumetry and navigation distance errors were also calculated. Compared with the controls, the SCD subjects performed worse in both egocentric and allocentric navigation. The SCD group showed volume reductions in the whole BF (p < 0.05, uncorrected) and the Ch4p subfield (p < 0.05, Bonferroni corrected), but comparable EC and hippocampal volumes with the controls. In the SCD cohort, the allocentric errors were negatively correlated with total BF (r = -0.625, p < 0.001), Ch4p (r = -0.625, p < 0.001), total EC (r = -0.423, p = 0.031), and left EC volumes (r = -0.442, p = 0.024), adjusting for age, gender, years of education, total intracranial volume, and hippocampal volume. This study demonstrates that SN deficits and BF atrophy may be promising indicators for the early detection of incipient AD patients. The reduced BF volume, especially in the Ch4p subfield, may serve as a structural basis for allocentric disorientation in SCD subjects independent of hippocampal atrophy. Our findings may have further implications for the preclinical diagnosis and intervention for potential AD patients.

• Keywords
• allocentric, basal forebrain, entorhinal cortex, spatial navigation, subjective cognitive decline,
• Publication type
• Journal Article MeSH

Spatial reference frames (RFs) play a key role in spatial cognition, especially in perception, spatial memory, and navigation. There are two main types of RFs: egocentric (self-centered) and allocentric (object-centered). Although many fMRI studies examined the neural correlates of egocentric and allocentric RFs, they could not sample the fast temporal dynamics of the underlying cognitive processes. Therefore, the interaction and timing between these two RFs remain unclear. Taking advantage of the high temporal resolution of intracranial EEG (iEEG), we aimed to determine the timing of egocentric and allocentric information processing and describe the brain areas involved. We recorded iEEG and analyzed broad gamma activity (50-150 Hz) in 37 epilepsy patients performing a spatial judgment task in a three-dimensional circular virtual arena. We found overlapping activation for egocentric and allocentric RFs in many brain regions, with several additional egocentric- and allocentric-selective areas. In contrast to the egocentric responses, the allocentric responses peaked later than the control ones in frontal regions with overlapping selectivity. Also, across several egocentric or allocentric selective areas, the egocentric selectivity appeared earlier than the allocentric one. We identified the maximum number of egocentric-selective channels in the medial occipito-temporal region and allocentric-selective channels around the intraparietal sulcus in the parietal cortex. Our findings favor the hypothesis that egocentric spatial coding is a more primary process, and allocentric representations may be derived from egocentric ones. They also broaden the dominant view of the dorsal and ventral streams supporting egocentric and allocentric space coding, respectively.

• Keywords
• Allocentric, Egocentric, High-frequency gamma activity, Intracranial EEG, Reference frames, Spatial judgment,
• MeSH
• Electrocorticography MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Judgment physiology   MeSH
• Spatial Processing * MeSH
• Space Perception * physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

AIMS: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI). METHODS: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly participants (HE, n = 22). They completed the Mini-Mental State Examination and a virtual Hidden Goal Task in egocentric, allocentric, and delayed recall subtests. RESULTS: In allocentric navigation, aMCI and comMCI performed significantly worse than HE and similarly to each other. Although aMCI performed significantly worse at egocentric navigation than HE, they performed significantly better than patients with comMCI. CONCLUSIONS: Despite the growing burden of dementia and the prevalence of neuropsychiatric symptoms in the elderly population, comMCI remains under-studied. Since trials often assess "pure" aMCI, we may underestimate patients' navigation and other deficits. This finding emphasizes the importance of taking account of the cognitive effects of psychiatric disorders in aMCI.

• Keywords
• Mild cognitive impairment, neuropsychiatric comorbidity, spatial memory, spatial navigation,
• MeSH
• Amnesia epidemiology   psychology   MeSH
• Cognitive Dysfunction epidemiology   psychology   MeSH
• Comorbidity MeSH
• Humans MeSH
• Spatial Navigation * MeSH
• Spatial Memory MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Cognitive deficits are common in early multiple sclerosis (MS), however, spatial navigation changes and their associations with brain pathology remain poorly understood. OBJECTIVE: To characterize the profile of spatial navigation changes in two main navigational strategies, egocentric (self-centred) and allocentric (world-centred), and their associations with demyelinating and neurodegenerative changes in early MS. METHODS: Participants with early MS after the first clinical event (n = 51) and age-, gender- and education-matched controls (n = 42) underwent spatial navigation testing in a real-space human analogue of the Morris water maze task, comprehensive neuropsychological assessment, and MRI brain scan with voxel-based morphometry and volumetric analyses. RESULTS: The early MS group had lower performance in the egocentric (p = 0.010), allocentric (p = 0.004) and allocentric-delayed (p = 0.038) navigation tasks controlling for age, gender and education. Based on the applied criteria, lower spatial navigation performance was present in 26-29 and 33-41% of the participants with early MS in the egocentric and the allocentric task, respectively. Larger lesion load volume in cortical, subcortical and cerebellar regions (ß ≥ 0.29; p ≤ 0.032) unlike brain atrophy was associated with less accurate allocentric navigation performance. CONCLUSION: Lower spatial navigation performance is present in up to 41% of the participants with early MS. Demyelinating lesions in early MS may disrupt neural network forming the basis of allocentric navigation.

• Keywords
• Allocentric, Cognition, Egocentric, Lesion load, MRI, Neuropsychology, Volumetry, Voxel-based morphometry,
• MeSH
• Cognition MeSH
• Cognitive Dysfunction * MeSH
• Humans MeSH
• Neuropsychological Tests MeSH
• Spatial Navigation * MeSH
• Multiple Sclerosis * diagnostic imaging   MeSH
• Space Perception MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Spatial navigation is a skill of determining and maintaining a trajectory from one place to another. Mild progressive decline of spatial navigation develops gradually during the course of physiological ageing. Nevertheless, severe spatial navigation deficit can be the first sign of incipient Alzheimer's disease (AD), occurring in the stage of mild cognitive impairment (MCI), preceding the development of a full blown dementia. Patients with amnestic MCI, especially those with the hippocampal type of amnestic syndrome, are at very high risk of AD. These patients present with the same pattern of spatial navigation impairment as do the patients with mild AD. Spatial navigation testing of elderly as well as computer tests developed for routine clinical use thus represents a possibility for further investigation of this cognitive domain, but most of all, an opportunity for making early diagnosis of AD.

• Keywords
• Alzheimer's disease, allocentric navigation, egocentric navigation, mild cognitive impairment, pathological ageing, physiological ageing, spatial navigation,
• Publication type
• Journal Article MeSH

Hippocampal and basal forebrain (BF) atrophy is associated with allocentric navigation impairment in Alzheimer's disease (AD) and may lead to recruitment of compensatory navigation strategies. We examined navigation strategy preference, its association with allocentric navigation, and the role of hippocampal and BF volumes in this association in early clinical stages of AD. Sixty nine participants-amnestic mild cognitive impairment (aMCI) due to AD (n = 28), AD dementia (n = 21), and cognitively normal (CN) older adults (n = 20)-underwent virtual Y-maze strategy assessment, real-space navigation testing, cognitive assessment, and hippocampal and BF volumetry. Preference for egocentric over allocentric strategy increased with AD severity (aMCI: 67% vs. 33%; dementia: 94% vs. 6%), which contrasted with preference in the CN group (39% vs. 61%). Those with aMCI who preferred egocentric strategy had worse allocentric navigation. Among those with aMCI, hippocampal and BF atrophy explained up to 25% of the association between strategy preference and allocentric navigation. The preference for egocentric strategy in AD may reflect recruitment of compensatory extrahippocampal navigation strategies as adaptation to hippocampal and BF neurodegeneration.

• Keywords
• Allocentric, Basal forebrain, Egocentric, Hippocampus, Mild cognitive impairment, Navigation, Strategy,
• MeSH
• Alzheimer Disease pathology   psychology   MeSH
• Atrophy MeSH
• Maze Learning MeSH
• Nerve Degeneration MeSH
• Hippocampus pathology   physiopathology   MeSH
• Cognitive Dysfunction pathology   psychology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neuropsychological Tests MeSH
• Basal Forebrain pathology   physiopathology   MeSH
• Spatial Navigation physiology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Organ Size MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Spatial navigation (SN) impairment is present early in Alzheimer's disease (AD). We tested whether SN performance, self-centered (egocentric) and world-centered (allocentric), was distinguishable from performance on established cognitive functions-verbal and nonverbal memory, executive and visuospatial function, attention/working memory, and language function. 108 older adults (53 cognitively normal [CN] and 55 with amnestic mild cognitive impairment [aMCI]) underwent neuropsychological examination and real-space navigation testing. Subset (n = 63) had automated hippocampal volumetry. In a factor analysis, allocentric and egocentric navigation tasks loaded highly onto the same factor with low loadings on other factors comprising other cognitive functions. In linear regression, performance on other cognitive functions was not, or was only marginally, associated with spatial navigation performance in CN or aMCI groups. After adjustment for age, gender, and education, right hippocampal volume explained 26% of the variance in allocentric navigation in aMCI group. In conclusion, spatial navigation, a known cognitive marker of early AD, may be distinguished from other cognitive functions. Therefore, its assessment along with other major cognitive functions may be highly beneficial in terms of obtaining a comprehensive neuropsychological profile.

• Keywords
• Alzheimer's disease, Hippocampus, Mild cognitive impairment, Morris Water Maze, Neuropsychology, Spatial navigation,
• MeSH
• Hippocampus diagnostic imaging   pathology   MeSH
• Cognition physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Memory physiology   MeSH
• Spatial Navigation physiology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Aging pathology   psychology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOEɛ4 carriers but its role in APOEɛ4-related spatial navigation deficits has not been established. OBJECTIVE: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI). METHODS: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4-/BDNFVal/Val, ɛ4-/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze. RESULTS: Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4-/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4-/BDNFVal/Val (p≤0.019) and ɛ4-/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4-/BDNFVal/Val group (p < 0.05). CONCLUSION: The combination of APOEɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.

• Keywords
• Alzheimer’s disease, Morris water maze, apolipoproteins E, brain-derived neurotrophic factor, entorhinal cortex, episodic memory, gene polymorphism, magnetic resonance imaging, mild cognitive impairment, spatial navigation,
• MeSH
• Apolipoprotein E4 genetics   MeSH
• Cognitive Dysfunction genetics   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Brain-Derived Neurotrophic Factor genetics   MeSH
• Polymorphism, Genetic MeSH
• Spatial Navigation physiology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Apolipoprotein E4 MeSH
• BDNF protein, human MeSH Browser
• Brain-Derived Neurotrophic Factor MeSH

BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.

• Keywords
• Allocentric navigation, Amyloid-β, Egocentric navigation, Entorhinal cortex, Hippocampus, Tau protein,
• MeSH
• Alzheimer Disease * genetics   cerebrospinal fluid   diagnostic imaging   complications   physiopathology   pathology   MeSH
• Amyloid beta-Peptides cerebrospinal fluid   MeSH
• Apolipoprotein E4 * genetics   MeSH
• Apolipoproteins E * genetics   MeSH
• Atrophy MeSH
• Biomarkers cerebrospinal fluid   MeSH
• Genotype MeSH
• Cognitive Dysfunction * genetics   cerebrospinal fluid   diagnostic imaging   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain pathology   diagnostic imaging   MeSH
• Neuropsychological Tests MeSH
• Peptide Fragments cerebrospinal fluid   MeSH
• Positron-Emission Tomography MeSH
• Spatial Navigation * physiology   MeSH
• tau Proteins cerebrospinal fluid   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• amyloid beta-protein (1-42) MeSH Browser
• Amyloid beta-Peptides MeSH
• Apolipoprotein E4 * MeSH
• Apolipoproteins E * MeSH
• Biomarkers MeSH
• Peptide Fragments MeSH
• tau Proteins MeSH