Research

17 pages, 3434 KiB

Open AccessArticle

Genetic Insights into Obesity and Brain: Combine Mendelian Randomization Study and Gene Expression Analysis

by Leian Chen, Shaokun Zhao, Yuye Wang, Xiaoqian Niu, Bin Zhang, Xin Li and Dantao Peng

Brain Sci. 2023, 13(6), 892; https://doi.org/10.3390/brainsci13060892 - 31 May 2023

Cited by 1 | Viewed by 2349

As a major public-health concern, obesity is imposing an increasing social burden around the world. The link between obesity and brain-health problems has been reported, but controversy remains. To investigate the relationship among obesity, brain-structure changes and diseases, a two-stage analysis was performed. [...] Read more.

As a major public-health concern, obesity is imposing an increasing social burden around the world. The link between obesity and brain-health problems has been reported, but controversy remains. To investigate the relationship among obesity, brain-structure changes and diseases, a two-stage analysis was performed. At first, we used the Mendelian-randomization (MR) approach to identify the causal relationship between obesity and cerebral structure. Obesity-related data were retrieved from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and the UK Biobank, whereas the cortical morphological data were from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. Further, we extracted region-specific expressed genes according to the Allen Human Brian Atlas (AHBA) and carried out a series of bioinformatics analyses to find the potential mechanism of obesity and diseases. In the univariable MR, a higher body mass index (BMI) or larger visceral adipose tissue (VAT) was associated with a smaller global cortical thickness (p_BMI = 0.006, p_VAT = 1.34 × 10⁻⁴). Regional associations were found between obesity and specific gyrus regions, mainly in the fusiform gyrus and inferior parietal gyrus. Multivariable MR results showed that a greater body fat percentage was linked to a smaller fusiform-gyrus thickness (p = 0.029) and precuneus surface area (p = 0.035). As for the gene analysis, region-related genes were enriched to several neurobiological processes, such as compound transport, neuropeptide-signaling pathway, and neuroactive ligand–receptor interaction. These genes contained a strong relationship with some neuropsychiatric diseases, such as Alzheimer’s disease, epilepsy, and other disorders. Our results reveal a causal relationship between obesity and brain abnormalities and suggest a pathway from obesity to brain-structure abnormalities to neuropsychiatric diseases. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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11 pages, 615 KiB

Open AccessArticle

Associations between Autonomic Function and Cognitive Performance among Patients with Cerebral Small Vessel Disease

by Guoliang Hu, Jean-Paul Collet, Mengxi Zhao, Yao Lu and Yilong Wang

Brain Sci. 2023, 13(2), 344; https://doi.org/10.3390/brainsci13020344 - 17 Feb 2023

Cited by 3 | Viewed by 1415

Abstract

Data linking heart rate variability (HRV) and cognitive status remains controversial and scarce, particularly in cerebral small vessel disease (CSVD) patients. Whether the association between HRV and cognitive performance exists in CSVD patients is unclear. Hence, we aimed to investigate the association between [...] Read more.

Data linking heart rate variability (HRV) and cognitive status remains controversial and scarce, particularly in cerebral small vessel disease (CSVD) patients. Whether the association between HRV and cognitive performance exists in CSVD patients is unclear. Hence, we aimed to investigate the association between HRV and cognitive performance in patients with CSVD. This cross-sectional study was conducted among 117 CSVD patients. All patients underwent HRV assessment and global cognitive evaluation by the Mini-Mental-State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Multivariable analyses were performed to evaluate the association between HRV and cognitive status. The mean age of study population was 59.5 ± 11.8 years and 39.3% were female. After adjusting for confounding factors, a higher high frequency (HF) norm was independently associated with better MMSE scores (β = 0.051; 95% confidence interval (CI): 0.012~0.090; p = 0.011) and MoCA scores (β = 0.061; 95% CI: 0.017~0.105; p = 0.007), while a higher low frequency (LF)/HF ratio was independently associated with worse MMSE scores (β = −0.492; 95% CI: −0.893~−0.092; p = 0.017) and MoCA scores (β = −0.691; 95% CI: −1.134~−0.248; p = 0.003). The HF norm was positively associated with global cognitive performance, whereas the LF/HF ratio was negatively associated with global cognitive performance among CSVD patients. Further study of the relationship between autonomic function and cognitive performance is warranted. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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14 pages, 3196 KiB

Open AccessArticle

Applying Retinal Vascular Structures Characteristics Coupling with Cortical Visual System in Alzheimer’s Disease Spectrum Patients

by Lianlian Wang, Zheqi Hu, Haifeng Chen, Xiaoning Sheng, Ruomeng Qin, Pengfei Shao, Zhiyuan Yang, Weina Yao, Hui Zhao, Yun Xu and Feng Bai

Brain Sci. 2023, 13(2), 339; https://doi.org/10.3390/brainsci13020339 - 16 Feb 2023

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Abstract

Cortical visual system dysfunction is closely related to the progression of Alzheimer’s Disease (AD), while retinal vascular structures play an important role in the integrity of the function of the visual network and are a potential biomarker of AD. This study explored the [...] Read more.

Cortical visual system dysfunction is closely related to the progression of Alzheimer’s Disease (AD), while retinal vascular structures play an important role in the integrity of the function of the visual network and are a potential biomarker of AD. This study explored the association between the cortical visual system and retinal vascular structures in AD-spectrum patients, and it established a screening tool to detect preclinical AD based on these parameters identified in a retinal examination. A total of 42 subjects were enrolled and were distributed into two groups: 22 patients with cognitive impairment and 20 healthy controls. All participants underwent neuropsychological tests, optical coherence tomography angiography and resting-state fMRI imaging. Seed-based functional connectivity analysis was used to construct the cortical visual network. The association of functional connectivity of the cortical visual system and retinal vascular structures was further explored in these subjects. This study found that the cognitive impairment group displayed prominently decreased functional connectivity of the cortical visual system mainly involving the right inferior temporal gyrus, left supramarginal gyrus and right postcentral gyrus. Meanwhile, we observed that retinal vascular structure characteristics deteriorated with the decline in functional connectivity in the cortical visual system. Our study provided novel insights into the aberrant cortical visual system in patients with cognitive impairment that strongly emphasized the critical role of retinal vascular structure characteristics, which could be used as potential biomarkers for diagnosing and monitoring the progression of AD. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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15 pages, 5809 KiB

Open AccessArticle

Effective Connectivity Evaluation of Resting-State Brain Networks in Alzheimer’s Disease, Amnestic Mild Cognitive Impairment, and Normal Aging: An Exploratory Study

by Fatemeh Mohammadian, Maryam Noroozian, Arash Zare Sadeghi, Vahid Malekian, Azam Saffar, Mahsa Talebi, Hasan Hashemi, Hanieh Mobarak Salari, Fardin Samadi, Forough Sodaei and Hamidreza Saligheh Rad

Brain Sci. 2023, 13(2), 265; https://doi.org/10.3390/brainsci13020265 - 04 Feb 2023

Cited by 1 | Viewed by 2351

Abstract

(1) Background: Alzheimer’s disease (AD) is a neurodegenerative disease with a high prevalence. Despite the cognitive tests to diagnose AD, there are pitfalls in early diagnosis. Brain deposition of pathological markers of AD can affect the direction and intensity of the signaling. The [...] Read more.

(1) Background: Alzheimer’s disease (AD) is a neurodegenerative disease with a high prevalence. Despite the cognitive tests to diagnose AD, there are pitfalls in early diagnosis. Brain deposition of pathological markers of AD can affect the direction and intensity of the signaling. The study of effective connectivity allows the evaluation of intensity flow and signaling pathways in functional regions, even in the early stage, known as amnestic mild cognitive impairment (aMCI). (2) Methods: 16 aMCI, 13 AD, and 14 normal subjects were scanned using resting-state fMRI and T1-weighted protocols. After data pre-processing, the signal of the predefined nodes was extracted, and spectral dynamic causal modeling analysis (spDCM) was constructed. Afterward, the mean and standard deviation of the Jacobin matrix of each subject describing effective connectivity was calculated and compared. (3) Results: The maps of effective connectivity in the brain networks of the three groups were different, and the direction and strength of the causal effect with the progression of the disease showed substantial changes. (4) Conclusions: Impaired information flow in the resting-state networks of the aMCI and AD groups was found versus normal groups. Effective connectivity can serve as a potential marker of Alzheimer’s pathophysiology, even in the early stages of the disease. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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19 pages, 2638 KiB

Open AccessArticle

Decreased Brain Structural Network Connectivity in Patients with Mild Cognitive Impairment: A Novel Fractal Dimension Analysis

by Chi Ieong Lau, Jiann-Horng Yeh, Yuh-Feng Tsai, Chen-Yu Hsiao, Yu-Te Wu and Chi-Wen Jao

Brain Sci. 2023, 13(1), 93; https://doi.org/10.3390/brainsci13010093 - 03 Jan 2023

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Abstract

Mild cognitive impairment (MCI) is widely regarded to be the intermediate stage to Alzheimer’s disease. Cerebral morphological alteration in cortical subregions can provide an accurate predictor for early recognition of MCI. Thirty patients with MCI and thirty healthy control subjects participated in this [...] Read more.

Mild cognitive impairment (MCI) is widely regarded to be the intermediate stage to Alzheimer’s disease. Cerebral morphological alteration in cortical subregions can provide an accurate predictor for early recognition of MCI. Thirty patients with MCI and thirty healthy control subjects participated in this study. The Desikan–Killiany cortical atlas was applied to segment participants’ cerebral cortex into 68 subregions. A complexity measure termed fractal dimension (FD) was applied to assess morphological changes in cortical subregions of participants. The MCI group revealed significantly decreased FD values in the bilateral temporal lobes, right parietal lobe including the medial temporal, fusiform, para hippocampal, and also the orbitofrontal lobes. We further proposed a novel FD-based brain structural network to compare network parameters, including intra- and inter-lobular connectivity between groups. The control group had five modules, and the MCI group had six modules in their brain networks. The MCI group demonstrated shrinkage of modular sizes with fewer components integrated, and significantly decreased global modularity in the brain network. The MCI group had lower intra- and inter-lobular connectivity in all lobes. Between cerebral lobes, the MCI patients may maintain nodal connections between both hemispheres to reduce connectivity loss in the lateral hemispheres. The method and results presented in this study could be a suitable tool for early detection of MCI. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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13 pages, 1335 KiB

Open AccessArticle

Pulse Pressure Is Associated with Rapid Cognitive Decline over 4 Years: A Population-Based Cohort Study

by Rong Zhou, Shan Wei, Yanyu Wang, Ling Gao, Liangjun Dang, Suhang Shang, Ningwei Hu, Wei Peng, Yi Zhao, Ye Yuan, Jingyi Wang, Jin Wang and Qiumin Qu

Brain Sci. 2022, 12(12), 1691; https://doi.org/10.3390/brainsci12121691 - 09 Dec 2022

Cited by 2 | Viewed by 1272

Abstract

Aiming to investigate the relationship between pulse pressure (PP) and cognitive decline, cognitively normal subjects from a community-based longitudinal cohort were followed-up for 4 years. The Mini-Mental State Examination (MMSE) was used to evaluate global cognitive function, and a ≥2-point decrease in the [...] Read more.

Aiming to investigate the relationship between pulse pressure (PP) and cognitive decline, cognitively normal subjects from a community-based longitudinal cohort were followed-up for 4 years. The Mini-Mental State Examination (MMSE) was used to evaluate global cognitive function, and a ≥2-point decrease in the MMSE score from baseline was defined as cognitive decline. Restricted cubic spline, multivariable linear regression and logistic regression were used to investigate the relationship between PP and cognitive decline. A total of 1173 participants completed the follow-up, and 205 (17.5%) met the criteria for cognitive decline. Restricted cubic splines showed no nonlinear relationship between PP and ΔMMSE (P_overall = 0.037, P_non-linear = 0.289) or cognitive decline (P_overall = 0.003, P_non-linear = 0.845). Multivariable linear regression analysis showed that PP was positively related to ΔMMSE (b = 0.021, p = 0.020). Multivariable logistic regression analysis showed that PP was positively associated with cognitive decline (OR = 1.020, p = 0.023). A stratified analysis found an association between PP and cognitive decline in participants who were aged ≤65 years, male, and APOEε4 noncarriers and who had school education ≤6 years or hypertension. A sensitivity analysis after propensity-score matching did not alter our findings. These findings highlight that elevated PP is associated with rapid cognitive decline, particularly in males, middle-aged, low-educated, hypertensive individuals and APOEε4 noncarriers. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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Review

Jump to: Research, Other

22 pages, 1096 KiB

Open AccessEditor’s ChoiceReview

Current and Future Nano-Carrier-Based Approaches in the Treatment of Alzheimer’s Disease

by Astik Kumar, Sachithra Thazhathuveedu Sudevan, Aathira Sujathan Nair, Ashutosh Kumar Singh, Sunil Kumar, Jobin Jose, Tapan Behl, Sabitha Mangalathillam, Bijo Mathew and Hoon Kim

Brain Sci. 2023, 13(2), 213; https://doi.org/10.3390/brainsci13020213 - 27 Jan 2023

Cited by 4 | Viewed by 2564

Abstract

It is a very alarming situation for the globe because 55 million humans are estimated to be affected by Alzheimer’s disease (AD) worldwide, and still it is increasing at the rapid speed of 10 million cases per year worldwide. This is an urgent [...] Read more.

It is a very alarming situation for the globe because 55 million humans are estimated to be affected by Alzheimer’s disease (AD) worldwide, and still it is increasing at the rapid speed of 10 million cases per year worldwide. This is an urgent reminder for better research and treatment due to the unavailability of a permanent medication for neurodegenerative disorders like AD. The lack of drugs for neurodegenerative disorder treatment is due to the complexity of the structure of the brain, mainly due to blood–brain barrier, because blood–brain drug molecules must enter the brain compartment. There are several novel and conventional formulation approaches that can be employed for the transportation of drug molecules to the target site in the brain, such as oral, intravenous, gene delivery, surgically implanted intraventricular catheter, nasal and liposomal hydrogels, and repurposing old drugs. A drug’s lipophilicity influences metabolic activity in addition to membrane permeability because lipophilic substances have a higher affinity for metabolic enzymes. As a result, the higher a drug’s lipophilicity is, the higher its permeability and metabolic clearance. AD is currently incurable, and the medicines available merely cure the symptoms or slow the illness’s progression. In the next 20 years, the World Health Organization (WHO) predicts that neurodegenerative illnesses affecting motor function will become the second-leading cause of mortality. The current article provides a brief overview of recent advances in brain drug delivery for AD therapy. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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Jump to: Research, Review

8 pages, 773 KiB

Open AccessStudy Protocol

Effects of Long-Term Oral Administration of N-Palmitoylethanolamine in Subjects with Mild Cognitive Impairment: Study Protocol

by Michela Bossa, Ornella Argento, Chiara Piacentini, Nicola Manocchio, Lucia Scipioni, Sergio Oddi, Mauro Maccarrone and Ugo Nocentini

Brain Sci. 2023, 13(8), 1138; https://doi.org/10.3390/brainsci13081138 - 29 Jul 2023

Viewed by 1002

Abstract

N-palmitoylethanolamine (PEA) plays a key role in preventing Aβ-mediated neuroinflammation and neurotoxicity in murine models. It has been demonstrated that PEA provides anti-neuroinflammatory, pain-relieving and neuroprotective actions even in humans. In this project, we aim to evaluate these anti-neuroinflammatory effects via the [...] Read more.

N-palmitoylethanolamine (PEA) plays a key role in preventing Aβ-mediated neuroinflammation and neurotoxicity in murine models. It has been demonstrated that PEA provides anti-neuroinflammatory, pain-relieving and neuroprotective actions even in humans. In this project, we aim to evaluate these anti-neuroinflammatory effects via the cognitive evaluation and biochemical analyses of a 12-month oral administration of PEA in subjects with mild cognitive impairment (MCI). Subjects with MCI will be randomized to placebo or PEA groups, and followed for another 6 months. Cognitive abilities and neurological inflammation will be examined at baseline and after treatment. The specific objectives of the project are to ascertain whether: (i) PEA influences the scores of the neuropsychological and behavioral evaluations after one-year treatment, comparing PEA-treated and placebo subjects in both MCI and control groups; (ii) PEA can change the inflammatory and neuronal damage markers of blood and urine in MCI subjects; and (iii) these changes correlate with the clinical scores of participating subjects. Full article

(This article belongs to the Special Issue Cognitive Function and Alzheimer’s Disease)

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