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.

• Klíčová slova
• 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 genetika   MeSH
• kognitivní dysfunkce genetika   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozkový neurotrofický faktor genetika   MeSH
• polymorfismus genetický MeSH
• prostorová navigace fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoprotein E4 MeSH
• BDNF protein, human MeSH Prohlížeč
• mozkový neurotrofický faktor MeSH

Impairment of spatial navigation (SN) skills is one of the features of the Alzheimer's disease (AD) already at the stage of mild cognitive impairment (MCI). We used a computer-based battery of spatial navigation tests to measure the SN performance in 22 MCI patients as well as 21 normal controls (NC). In order to evaluate intrinsic activity in the subcortical regions that may play a role in SN, we measured ALFF, fALFF, and ReHo derived within 14 subcortical regions. We observed reductions of intrinsic activity in MCI patients. We also demonstrated that the MCI versus NC group difference can modulate activity-behavior relationship, that is, the correlation slopes between ReHo and allocentric SN task total errors were significantly different between NC and MCI groups in the right hippocampus (interaction F = 4.44, p = 0.05), pallidum (F = 8.97, p = 0.005), and thalamus (F = 5.95, p = 0.02), which were negative in NC (right hippocampus, r = -0.49; right pallidum, r = -0.50; right thalamus, r = -0.45; all p < 0.05) but absent in MCI (right hippocampus, r = 0.21; right pallidum, r = 0.32; right thalamus r = 0.28; all p > 0.2). These findings may provide a novel insight of the brain mechanism associated with SN impairment in MCI and indicated a stage specificity of brain-behavior correlation in dementia. This trial is registered with ChiCTR-BRC-17011316.

• MeSH
• dospělí MeSH
• funkční zobrazování neurálních procesů MeSH
• globus pallidus diagnostické zobrazování   patofyziologie   MeSH
• hipokampus diagnostické zobrazování   patofyziologie   MeSH
• kognitivní dysfunkce diagnostické zobrazování   patofyziologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• neuropsychologické testy MeSH
• prostorová navigace fyziologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thalamus diagnostické zobrazování   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. OBJECTIVES: We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. METHODS: We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. RESULTS: Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. CONCLUSIONS: In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.

• Klíčová slova
• Acetylcholinesterase inhibitor *, Human *, Rat *, Scopolamine *, Spatial orientation *,
• MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• bludiště - učení účinky léků   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• donepezil MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• indany farmakologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mladý dospělý MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• prostorová navigace účinky léků   MeSH
• skopolamin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté muskarinových receptorů MeSH
• cholinesterasové inhibitory MeSH
• donepezil MeSH
• indany MeSH
• piperidiny MeSH
• skopolamin MeSH

• Klíčová slova
• animal models, clinical studies, cognition, neuropsychiatric disorders, preclinical studies,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer's disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored. OBJECTIVES: To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls. PATIENTS AND METHODS: A total of 114 patients, 13 with single domain (SD-aMCI) and 30 with multiple domains (MD-aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI. RESULTS: Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls. CONCLUSIONS: Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD-aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus.

• MeSH
• Alzheimerova nemoc diagnóza   psychologie   MeSH
• emoce MeSH
• kognitivní dysfunkce * MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• rozpoznávání (psychologie) MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spánkový lalok patologie   MeSH
• výraz obličeje MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH