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Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE) gene is a strong risk factor for AD.
BACKGROUND
Alzheimer's disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE) gene is a strong risk factor for AD.
OBJECTIVE
Here, we explored alterations in grey matter structure (GMV) and networks in AD, as well as the effects of the APOEɛ4 allele on neuroimaging regions based on structural magnetic resonance imaging (sMRI).
METHODS
All subjects underwent an sMRI scan. GMV and cortical thickness were calculated using voxel-based morphological analysis, and structural networks were constructed based on graph theory analysis to compare differences between AD and normal controls.
RESULTS
The volumes of grey matter in the bilateral inferior temporal gyrus, right middle temporal gyrus, right inferior parietal lobule, right limbic lobe, right frontal lobe, left anterior cingulate gyrus, and bilateral olfactory cortex of patients with AD were significantly decreased. The cortical thickness in patients with AD was significantly reduced in the left lateral occipital lobe, inferior parietal lobe, orbitofrontal region, precuneus, superior parietal gyrus, right precentral gyrus, middle temporal gyrus, pars opercularis gyrus, insular gyrus, superior marginal gyrus, bilateral fusiform gyrus, and superior frontal gyrus. In terms of local properties, there were significant differences between the AD and control groups in these areas, including the right bank, right temporalis pole, bilateral middle temporal gyrus, right transverse temporal gyrus, left postcentral gyrus, and left parahippocampal gyrus.
CONCLUSION
There were significant differences in the morphological and structural covariate networks between AD patients and healthy controls under APOEɛ4 allele effects.
Topics: Humans; Alzheimer Disease; Apolipoprotein E4; Brain; Gray Matter; Magnetic Resonance Imaging
PubMed: 36530087
DOI: 10.3233/JAD-220877 -
Parkinsonism & Related Disorders May 2024Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying...
INTRODUCTION
Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD.
METHODS
Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis.
RESULTS
Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus.
CONCLUSIONS
The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.
Topics: Humans; Parkinson Disease; Male; Female; Aged; Middle Aged; Longitudinal Studies; Magnetic Resonance Imaging; REM Sleep Behavior Disorder; Olfaction Disorders; Atrophy; Anosmia; Disease Progression; Brain
PubMed: 38430690
DOI: 10.1016/j.parkreldis.2024.106072 -
Cell & Bioscience May 2023Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry...
BACKGROUND
Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed.
METHODS
Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1 mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated.
RESULTS
In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum.
CONCLUSIONS
Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.
PubMed: 37147705
DOI: 10.1186/s13578-023-01032-4 -
Frontiers in Aging Neuroscience 2023The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition...
BACKGROUND
The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition interaction remains largely unknown.
METHODS
One hundred and twenty-seven participants, including 35 normal controls (NCs), 62 with subjective cognitive decline (SCD), and 30 with cognitive impairment (CI), were included in this study. The participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Structural MRI data were analyzed for cortical anatomical features, including thickness, sulcus depth, fractal dimension, and Toro's gyrification index using the SBM method. The association of altered gut microbiota among the three groups with structural MRI metrics and cognitive function was evaluated. Furthermore, co-expression network analysis was conducted to investigate the gut-brain-cognition interactions.
RESULTS
The abundance of , and decreased with cognitive ability. , and were specifically enriched in the CI group. abundance was correlated with changes in brain gray matter and cerebrospinal fluid volume ( = 0.0214, = 0.0162) and significantly with changes in cortical structures in brain regions, such as the internal olfactory area and the parahippocampal gyrus. The three colonies enriched in the CI group were positively correlated with cognitive function and significantly associated with changes in cortical structure related to cognitive function, such as the precuneus and syrinx gyrus.
CONCLUSION
This study provided evidence that there was an inner relationship among the altered gut microbiota, brain atrophy, and cognitive decline. Targeting the gut microbiota may be a novel therapeutic strategy for early AD.
PubMed: 37520126
DOI: 10.3389/fnagi.2023.1216509 -
Epilepsy & Behavior : E&B Feb 2024To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras.
OBJECTIVES
To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras.
MATERIALS AND METHODS
We conducted a monocentric, retrospective study on patients who underwent surgery in the Neurosurgery Unit of Udine University Hospital (Udine, Italy), between the 1st of January 2010 and the 1st of January 2019, for primary brain tumors (PBTs) involving the temporal lobe and the insula. All patients were affected by tumor-related epilepsy; the study group presented olfactory auras as well. We collected neuroradiological, neuropsychological and neurophysiological data from patients' medical charts.
RESULTS
The subtraction analysis of MRI data shows maximum lesion overlay in left olfactory cortex, left and right hippocampus, left amygdala, right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus. The presence of olfactory auras did not influence seizure outcome (p = 0.500) or tumor recurrence after surgery (p = 0.185). The type of auras (elementary vs. complex), also, did not influence seizure control (p = 0.222).
DISCUSSION
In presence of olfactory auras, anterior and mesial temporal regions are mainly involved, such as olfactory cortex, amygdala, and anterior hippocampus, together with right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus, suggesting their possible role in the genesis of olfactory auras. Post-surgical seizure outcome and disease relapse are not influenced by neither the presence nor the type of olfactory auras.
CONCLUSIONS
Olfactory auras are rare event, however they may be often underestimated by the patients and under-investigated by the clinicians, even when their occurrence can represent a useful localizing tool.
Topics: Humans; Epilepsy, Temporal Lobe; Odorants; Retrospective Studies; Epilepsy; Seizures; Neoplasms; Magnetic Resonance Imaging; Recurrence; Electroencephalography
PubMed: 38242066
DOI: 10.1016/j.yebeh.2024.109642 -
NeuroImage. Clinical 2022Subjective cognitive decline (SCD), one of the important clinical indicators for preclinical Alzheimer's disease (AD), is primarily defined as self-perceived cognitive...
BACKGROUNDS
Subjective cognitive decline (SCD), one of the important clinical indicators for preclinical Alzheimer's disease (AD), is primarily defined as self-perceived cognitive decline without objective evidence for cognitive impairment. However, the accuracy of their self-evaluation of cognition is unclear. This study sought to investigate the capacity for self-evaluation of own cognitive performance in SCD by applying an objective metamemory paradigm.
METHODS
147 individuals with SCD were classified into four subgroups by their subjective feeling of worse performance than peers or not (P+/-) and whether they have objectively slight cognitive impairment compared to normative data (S+/-). Metamemory scores, the amplitude of the low-frequency fluctuation (ALFF), fractional low-frequency fluctuation amplitude (fALFF), and cortical thickness were compared among four subgroups. Partial correlations between neuropsychological scores and neuroimaging measures were examined, controlling for age, sex, and education years.
RESULTS
SCD S+P- showed the worst performance in short-term delayed recall and the worst metamemory performance, indicated by the highest value in the degree of confidence of short-term delayed recall (DOC-N4) and long-term cued recall (DOC-N6) and the worst value in relative accuracy of judgments of short-term delayed recall (ROJ-N4). ALFF values in the bilateral superior medial frontal and olfactory cortices and the left superior orbitofrontal gyrus cortex were significantly higher in SCD P- compared with SCD P+ groups (all P < 0.05, FWE-corrected, cluster-wise level). A significant S × P interaction effect in the left hippocampus and middle cingulate cortex was found for the fALFF signals (all P < 0.05, FWE-corrected, cluster-wise level). Significant interaction and main effects on cortical thickness were reported. The parahippocampal and posterior cingulate cortices were significantly decreased in SCD S+P- (all P < 0.05).
CONCLUSION
SCD S+P- showed the worst episodic memory performance, altered metamemory capacity (overconfidence and less accuracy of judgment), and altered neuroimaging measures, though they had feelings of similar performance with peers. Our results indicate that metamemory capacity is affected in a subtype of SCD with reduced cortical thickness and intensity of regional spontaneous activity in key areas for metamemory processing.
Topics: Humans; Neuropsychological Tests; Magnetic Resonance Imaging; Cognitive Dysfunction; Cognition; Metacognition
PubMed: 36451360
DOI: 10.1016/j.nicl.2022.103255 -
Brain Sciences Jul 2022The present study aimed to investigate the association between the functional connectivity (FC) of the olfactory cortex and olfactory performance in Parkinson's disease...
The present study aimed to investigate the association between the functional connectivity (FC) of the olfactory cortex and olfactory performance in Parkinson's disease (PD). Eighty-two early PD patients and twenty-one healthy controls underwent structural and resting-state functional MRI scans, as well as neuropsychological assessments from the Parkinson's Progression Markers Initiative database. A whole brain voxel-wise regression analysis was conducted to evaluate the relationship between the FC of the entorhinal cortex (EC-FC) and olfactory performance. Then, a one-way ANCOVA, based on the regions of interest, was performed with SPSS to investigate the group differences and correlation analysis that were used to analyze the relationships between the FC and neuropsychological assessments. In addition, regression models were used to evaluate the risk factors for the decreased olfactory function. A significantly negative correlation was observed between the olfactory performance and the left EC-FC in the right dorsal cingulate gyrus (dCC) in patients. The PD patients with anosmia exhibited significantly higher FC values than the PD patients with normal olfaction or the PD patients with mild to moderate microsomia. Except for the olfactory performance, no significant correlation was detected between the neuropsychological assessments and the FC values. A linear regression analysis revealed that the increased FC and Geriatric Depression Scale are independently associated with lower the University of Pennsylvania Smell Identification Test scores. The current findings enhanced the understanding of olfactory dysfunction-related pathophysiological mechanisms in early PD and suggested that the left EC-FC in the right dCC may be a potential neuroimaging biomarker for olfactory performance.
PubMed: 35892404
DOI: 10.3390/brainsci12080963 -
Neurological Research Apr 2023We investigated the peripheral and central smell regions in patients with idiopathic intracranial hypertension (IIH) by cranial MRI.
OBJECTIVES
We investigated the peripheral and central smell regions in patients with idiopathic intracranial hypertension (IIH) by cranial MRI.
METHODS
In this retrospective study, cranial MRI images of 43 adult patients with IIH (Group 1) and 43 healthy adults without IIH (Group 2) were included. In both groups, peripheral [Olfactory bulb (OB) volume and Olfactory sulcus (OS) depth] and central smell regions (insular gyrus and corpus amygdala area, and thalamus volume) were measured in cranial MRI.
RESULTS
Bilateral OB volume and insular gyrus area, and right corpus amygdala and thalamus volumes of the IIH group were significantly lower than those of the control group (p < 0.05). In the IIH group, OB volume of the right side was significantly lower, and insular gyrus area of the right side was significantly higher than those of the left side (p < 0.05). In the IIH group, there were positive correlations between OB volumes; OS depths; insular gyrus areas; corpus amygdala areas; and thalamus volumes bilaterally (p < 0.05). In older patients, right OS depth and right corpus amygdala area decreased (p < 0.05).
CONCLUSION
In conclusion, IIH may be related to olfactory impairment. Cranial MRI images showed a decrease in peripheral (OB volume) and central (insular gyrus and corpus amygdala area and thalamus volume) smell regions. To prevent olfactory impairment in IIH patients, treatment should be done in IIH patients to decrease intracranial pressure. It is very important to prevent the circulation of CSF with increased pressure between the sheets of the olfactory nerve in IIH patients.
Topics: Adult; Humans; Aged; Smell; Pseudotumor Cerebri; Retrospective Studies; Olfaction Disorders; Magnetic Resonance Imaging; Olfactory Bulb; Intracranial Hypertension
PubMed: 36373831
DOI: 10.1080/01616412.2022.2146261 -
Cerebral Cortex (New York, N.Y. : 1991) Oct 2020The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better...
The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better its roles in emotion and its disorders. The medial OFC and ventromedial prefrontal cortex have direct connections with the pregenual and subgenual parts of the anterior cingulate cortex; all of which are reward-related areas. The lateral OFC (OFClat) and its closely connected right inferior frontal gyrus (rIFG) have direct connections with the supracallosal anterior cingulate cortex; all of which are punishment or nonreward-related areas. The OFClat and rIFG also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the OFClat and rIFG. Another key finding is that the ventromedial prefrontal cortex shares with the medial OFC especially strong outputs to the nucleus accumbens and olfactory tubercle, which comprise the ventral striatum, whereas the other regions have more widespread outputs to the striatum. Direct connections of the OFC and IFG were with especially the temporal pole part of the temporal lobe. The left IFG, which includes Broca's area, has direct connections with the left angular and supramarginal gyri.
Topics: Adult; Aged; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Neural Pathways; Prefrontal Cortex
PubMed: 32548630
DOI: 10.1093/cercor/bhaa160 -
Neuroscience Research Sep 2022New neurons are constantly generated in the olfactory bulb and the dentate gyrus of the hippocampus. The number of new cells depends on sensory experiences; an enriched...
New neurons are constantly generated in the olfactory bulb and the dentate gyrus of the hippocampus. The number of new cells depends on sensory experiences; an enriched odor environment increases neurogenesis and neural survival. The aim of this study was to investigate whether enriched olfactory stimuli affect neurogenesis of mitral and granule cells of the olfactory bulb and dentate gyrus, and whether respiratory activity accompanied by olfactory stimuli is associated with new cells in these regions. To this end, respiratory activity during enriched odor stimuli was continuously measured in mice and new cells were stained with 5-bromo-2'-deoxyuridine, which selectively labels proliferating cells. An enriched olfactory environment significantly increased neurogenesis of mitral and granule cells in the olfactory bulb, but not in the dentate gyrus. Additionally, an increase of new granule cells under the enriched odor condition was correlated to sniffing frequency power, which had a significantly different pattern from the no-odor condition. A high respiratory frequency with frequent odor stimuli may be associated with activation of granule cells to form inhibitory neurons and this active state might increase granule cell neurogenesis.
Topics: Animals; Mice; Neurogenesis; Neurons; Odorants; Olfactory Bulb; Smell
PubMed: 35636589
DOI: 10.1016/j.neures.2022.05.007