Cognitive impairment and associated factors among patients with diabetes mellitus in Africa: a systematic review and meta-analysis.

Background: Inappropriate management of blood sugar in patients with diabetes mellitus leads to micro-vascular and macro-vascular complications, subsequently leading to high morbidity and mortality rates. In addition, diabetes independently increases the occurrence of cognitive impairment complicated by dementia. Scientific evidence on the magnitude of cognitive impairment will provide a sound basis for the determination of healthcare needs and the planning of effective healthcare services. Despite this, there are no comprehensive data on the prevalence and associated factors of cognitive impairment among patients with diabetes in Africa. Methods: To identify relevant articles for this review, we searched PubMed, Cochrane Library, Science Direct, African Journals Online, and Google Scholar. After extraction, the data were imported into Stata software version 11 (Stata Corp., TX, USA) for further analysis. The random-effects model, specifically the DerSimonian and Laird (D+L) pooled estimation method, was used due to the high heterogeneity between the included articles. Begg's and Egger's regression tests were used to determine the evidence of publication bias. Sub-group analyses and sensitivity analyses were also conducted to handle heterogeneity. Results: The pooled prevalence of cognitive impairment among patients with diabetes in Africa is found to be 43.99% (95% CI: 30.15-57.83, p < 0.001). According to our analysis, primary level of education [pooled odds ratio (POR) = 6.08, 95% CI: 3.57-10.36, I 2 = 40.7%], poorly controlled diabetes mellitus (POR = 5.85, 95% CI: 1.64-20.92, I 2 = 87.8%), age above 60 years old (POR = 3.83, 95% 95% CI: 1.36-10.79, I 2 = 63.7%), and diabetes duration greater than 10 years (POR = 1.13; 95% CI: 1.07-1.19, I 2 = 0.0%) were factors associated with cognitive impairment among patients with diabetes. Conclusion: Based on our systematic review, individuals with diabetes mellitus exhibit a substantial prevalence rate (43.99%) of cognitive impairment. Cognitive impairment was found to be associated with factors such as primary level of education, poorly controlled diabetes mellitus, age above 60 years, and diabetes duration greater than 10 years. Developing suitable risk assessment tools is crucial to address uncontrolled hyperglycemia effectively. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024561484.

Identifying postoperative cognitive dysfunction after elective coronary artery bypass graft surgery in a tertiary centre in Malaysia.

Postoperative cognitive dysfunction (POCD) is a significant concern, with incidences reported up to 70% following cardiac surgery. Therefore, we aim to evaluate the incidence of POCD after elective coronary artery bypass graft (CABG) surgery at our single centre over a one-year period from August 2021 to July 2022. We included 34 patients in the study and conducted serial cognitive assessments up to three months post-surgery. Interestingly, our findings indicated an absence of POCD among patients who underwent elective CABG. Reasons contributing to this outcome are multifactorial, which may include the patients' younger age, higher educational levels, lack of pre-existing neurological disorders, meticulous intraoperative cerebral saturation monitoring, and the duration of aortic crossclamp and cardiopulmonary bypass time.

Establishment and evaluation of a clinical prediction model for cognitive impairment in patients with cerebral small vessel disease.

BACKGROUND: There are currently no effective prediction methods for evaluating the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD). AIMS: To investigate the risk factors for cognitive dysfunction in patients with CSVD and to construct a risk prediction model. METHODS: A retrospective study was conducted on 227 patients with CSVD. All patients were assessed by brain magnetic resonance imaging (MRI), and the Montreal Cognitive Assessment (MoCA) was used to assess cognitive status. In addition, the patient's medical records were also recorded. The clinical data were divided into a normal cognitive function group and a cognitive impairment group. A MoCA score < 26 (an additional 1 point for education < 12 years) is defined as cognitive dysfunction. RESULTS: A total of 227 patients (mean age 66.7 ± 6.99 years) with CSVD were included in this study, of whom 68.7% were male and 100 patients (44.1%) developed cognitive impairment. Age (OR = 1.070; 95% CI = 1.015 ~ 1.128, p < 0.05), hypertension (OR = 2.863; 95% CI = 1.438 ~ 5.699, p < 0.05), homocysteine(HCY) (OR = 1.065; 95% CI = 1.005 ~ 1.127, p < 0.05), lacunar infarct score(Lac_score) (OR = 2.732; 95% CI = 1.094 ~ 6.825, P < 0.05), and CSVD total burden (CSVD_score) (OR = 3.823; 95% CI = 1.496 ~ 9.768, P < 0.05) were found to be independent risk factors for cognitive decline in the present study. The above 5 variables were used to construct a nomogram, and the model was internally validated by using bootstrapping with a C-index of 0.839. The external model validation C-index was 0.867. CONCLUSIONS: The nomogram model based on brain MR images and clinical data helps in individualizing the probability of cognitive impairment progression in patients with CSVD.

The role of gut microbiota in chronic restraint stress-induced cognitive deficits in mice.

BACKGROUND: Chronic stress induces cognitive deficits. There is a well-established connection between the enteric and central nervous systems through the microbiota-gut-brain (MGB) axis. However, the effects of the gut microbiota on cognitive deficits remain unclear. The present study aimed to elucidate the microbiota composition in cognitive deficits and explore its potential in predicting chronic stress-induced cognitive deficits. METHODS: Mice were randomly divided into control and chronic restraint stress (CRS) groups. The mice subjected to CRS were further divided into cognitive deficit (CRS-CD) and non-cognitive deficit (CRS-NCD) groups using hierarchical cluster analysis of novel object recognition test results. The composition and diversity of the gut microbiota were analyzed. RESULTS: After being subjected to chronic restraint distress, the CRS-CD mice travelled shorter movement distances (p = 0.034 vs. CRS-NCD; p < 0.001 vs. control) and had a lower recognition index than the CRS-NCD (p < 0.0001 vs. CRS-NCD; p < 0.0001 vs. control) and control mice. The results revealed that 5 gut bacteria at genus levels were significantly different in the fecal samples of mice in the three groups. Further analyses demonstrated that Muricomes were not only significantly enriched in the CRS-CD group but also correlated with a decreased cognitive index. The area under the receiver operating curve of Muricomes for CRS-induced cognitive deficits was 0.96. CONCLUSIONS: Our study indicates that the composition of the gut microbiota is involved in the development of cognitive deficits induced by chronic restraint stress. Further analysis revealed that Muricomes have the potential to predict the development of chronic stress-induced cognitive deficits in mice.

Inhibition of ANGPTL8 protects against diabetes-associated cognitive dysfunction by reducing synaptic loss via the PirB signaling pathway.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS: The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS: Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION: Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Effects of a dual intervention (motor and virtual reality-based cognitive) on cognition in patients with mild cognitive impairment: a single-blind, randomized controlled trial.

BACKGROUND: The increase in cases of mild cognitive impairment (MCI) underlines the urgency of finding effective methods to slow its progression. Given the limited effectiveness of current pharmacological options to prevent or treat the early stages of this deterioration, non-pharmacological alternatives are especially relevant. OBJECTIVE: To assess the effectiveness of a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity of daily living (ADL) on cognitive functions and its impact on depression and the ability to perform such activities in patients with MCI. METHODS: Thirty-four older adults (men, women) with MCI were randomized to the experimental group (n = 17; 75.41 ± 5.76) or control (n = 17; 77.35 ± 6.75) group. Both groups received motor training, through aerobic, balance and resistance activities in group. Subsequently, the experimental group received cognitive training based on VR, while the control group received traditional cognitive training. Cognitive functions, depression, and the ability to perform activities of daily living (ADLs) were assessed using the Spanish versions of the Montreal Cognitive Assessment (MoCA-S), the Short Geriatric Depression Scale (SGDS-S), and the of Instrumental Activities of Daily Living (IADL-S) before and after 6-week intervention (a total of twelve 40-minutes sessions). RESULTS: Between groups comparison did not reveal significant differences in either cognitive function or geriatric depression. The intragroup effect of cognitive function and geriatric depression was significant in both groups (p < 0.001), with large effect sizes. There was no statistically significant improvement in any of the groups when evaluating their performance in ADLs (control, p = 0.28; experimental, p = 0.46) as expected. The completion rate in the experimental group was higher (82.35%) compared to the control group (70.59%). Likewise, participants in the experimental group reached a higher level of difficulty in the application and needed less time to complete the task at each level. CONCLUSIONS: The application of a dual intervention, through motor training prior to a cognitive task based on Immersive VR was shown to be a beneficial non-pharmacological strategy to improve cognitive functions and reduce depression in patients with MCI. Similarly, the control group benefited from such dual intervention with statistically significant improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931 .

Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Relationship between serum levels of folic acid and homocysteine with cognitive impairment in patients diagnosed with multiple sclerosis.

Multiple Sclerosis (MS), one of the most common neurological diseases, plays a major role in the ailments of adults. Studies on the role of homocysteine (Hcy) and folic acid in causing cognitive disorders in patients diagnosed with MS are still ongoing. This study aimed to evaluate the serum levels of folic acid and Hcy related to cognitive impairment in patients with multiple sclerosis. This prospective clinical study was conducted on 57 patients diagnosed with MS who were referred to Firoozgar Hospital, Tehran, Iran (Between November 2019 and September 2021). Demographic information and clinical characteristics of enrolled patients were recorded in a predesigned checklist. These characteristics were comprised of outcomes related to the Brief International Cognitive Assessment for MS, and the patient's Hcy and acid folic levels. Data were analyzed using SPSS version 25. Out of 57 enrolled patients, 39 subjects (68.4%) were female and 18 subjects (31.6%) were male, with a mean age of 36.87 ±â€…9.40 years old. In terms of disease time span, there was a mean duration of 3.80 ±â€…4.94 years (range: 1-23 years). There were no significant differences between the mean score of Brief International Cognitive Assessment for MS scale with patient's sex (P value: .88), and disease duration of patients (P value: .86). There was no significant relationship between the serum levels of acid folic and Hcy with cognitive impairment (P value > .05). The study results revealed that there were no significant relationships between the folic acid, Hcy levels, disease duration, and the type of MS disease with the severity of cognitive impairment. More randomized controlled clinical trials are needed to confirm the relationships between the folic acid and Hcy levels with cognitive impairment in patients with MS.

Mild Cognitive Impairment: Clinical Presentation and Short-Term Comparative Outcome of Patients With Potentially Modifiable and Nonmodifiable Risk Factors.

Objective: To estimate the prevalence and study the clinical presentation of mild cognitive impairment (MCI), assess its outcome in terms of cognition and quality of life, identify factors for reversion to baseline, and compare these factors in the modifiable and nonmodifiable risk factor groups.Methods: Individuals aged >50 years with memory/cognitive complaint(s) were screened using the Mini-Cog over 1 year (August 2018-August 2019). Those meeting the DSM-5 criteria for MCI were enrolled, and risk factors (modifiable and nonmodifiable) were noted. Assessments were done using the Hindi version of the Montreal Cognitive Assessment (H-MoCA), the Clinical Dementia Rating (CDR)-Hindi version, and the World Health Organization Quality of Life-Brief Hindi version. Treatment outcome was assessed at 6 months and compared between the risk factor groups. Factors for reversion of MCI were assessed.Results: A total of 124 patients (22.1% of 561 with cognitive complaints) had MCI, and 100 patients (50 patients from the modifiable group and 50 patients from the nonmodifiable group) completed the study. Depression (52%) and hypertension (48%) were common risk factors. End point cognition scores were similar in both groups, with quality of life better in the modifiable group (P = .023). Age was negatively correlated with cognition in total patients and the nonmodifiable group (r =0.283-0.420; P = .002-.004). In total patients, cognition moderately correlated with education and somewhat with quality of life; 31% and 57% reverted to normal on the MoCA and CDR scales, respectively, while 1 progressed to dementia. Reverters had higher baseline H-MoCA scores (odds ratio [OR] = 6.996; P < .001) and were treated with cholinesterase inhibitors + vitamin E (OR = 28.999; P = .007).Conclusion: Short-term outcome for both the modifiable and nonmodifiable risk factor groups was favorable. Higher education positively correlated with cognition, which itself predicted a better quality of life. Reverters of MCI had better baseline cognition and were treated with cholinesterase inhibitors + vitamin E.Prim Care Companion CNS Disord 2024;26(4):24m03708. Author affiliations are listed at the end of this article.

Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis.

OBJECTIVE: To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity. PATIENTS AND METHODS: We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA. RESULTS: The study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6). CONCLUSIONS: Patients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.

[Yigong San improves cognitive decline in a rat model of Alzheimer's disease by regulating intestinal microorganisms].

OBJECTIVE: To investigate the effect of Yigong San (YGS) on learning and memory abilities of rats with lipopolysaccharide (LPS)­induced cognitive decline and explore its possible mechanism in light of intestinal microbiota. METHODS: Forty SD rats were randomly divided into control group, model group, donepezil (1.3 mg/kg) group, and high-dose (5.25 g/kg) and low-dose (2.63 g/kg) YGS treatment groups. After 24 days of treatment with the corresponding drugs or water by gavage, the rats in the latter 4 groups received an intraperitoneal injection of LPS (0.5 mg/kg) to establish models of Alzheimer's disease (AD). Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus. The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing, and the levels of IL-6, TNF-α, and IL-1ß in the brain tissue and serum were detected using ELISA. RESULTS: Compared with the AD model group, the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling, reduced neuronal degeneration and necrosis in the hippocampus, lowered pathological score of cell damage, and decreased levels IL-6, TNF-α and IL-1ß in the brain tissue and serum. The YGS-treated rats showed also obvious reduction of Alpha diversity indicators (ACE and Chao1) of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae, which were involved in such metabolic signaling pathways as cell community prokaryotes, membrane transport, and energy metabolism. CONCLUSION: YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction, cofactors, and vitamin metabolism.

Vitamin B12 Deficiency-Induced Neuropathy and Cognitive and Motor Impairment in the Elderly: A Case Study.

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history.

Plain language titleA case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaintsPlain language summaryVitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery.

Vitamin B12 and Age-Related Cognitive Decline-Dementia and "Alzheimer's Disease".

This article is a commentary on the role of vitamin B12 in age-related cognitive decline, with a meta-commentary on the misuse of the term "Alzheimer's Disease." The article describes the historical origins of the term "Alzheimer's Disease" and argues that the term should be restricted to a narrower segment of the age-related dementia spectrum. The article also outlines the role of vitamin B12 in age-related cognitive decline and outlines the rationale for the treatment of B12 deficiency to address a potentially reversible factor in cognitive decline.

Age-Related Effects of AT1 Receptor Antagonist Losartan on Cognitive Decline in Spontaneously Hypertensive Rats.

Both hypertension and aging are known to increase the vulnerability of the brain to neurovascular damage, resulting in cognitive impairment. The present study investigated the efficacy of the antihypertensive drug losartan on age- and hypertension-associated cognitive decline and the possible mechanism underlying its effect in spontaneously hypertensive rats (SHRs). Losartan was administered (10 mg/kg, i.p. for 19 days) to 3- and 14-month-old SHRs. Age-matched Wistar rats were used as controls. Working memory, short-term object recognition, and spatial memory were assessed using the Y-maze, object recognition test (ORT) and radial arm maze (RAM) test. The expression of markers associated with aging, oxidative stress, and memory-related signaling was assessed in the frontal cortex (FC) and hippocampus. Motor activity measured over 24 h was not different between groups. Middle-aged vehicle-treated SHRs showed poorer performance in spontaneous alternation behavior (SAB) and activity in the first Y-maze test than their younger counterparts, suggesting age-related reduced "decision making" and reactivity in a novel environment. Losartan improved the age- and hypertension-induced decline in short-term recognition and spatial memory measured in the ORT and the second Y-maze test, particularly in the middle-aged rats, but was ineffective in the young adult rats. Changes in memory and age-related markers such as cAMP response element-binding protein (CREB) and amyloid-ß1-42 (Aß1-42) and increased oxidative stress were observed in the hippocampus but not in the FC between young adult and middle-aged vehicle-treated SHRs. Losartan increased CREB expression while reducing Aß1-42 levels and concomitant oxidative stress in middle-aged SHRs compared with vehicle-treated SHRs. In conclusion, our study highlights the complex interplay between hypertension, aging, and cognitive impairment. It suggests that there is a critical time window for therapeutic intervention with angiotensin II type 1 receptor blockers.

High baseline perivascular space volume in basal ganglia is associated with attention and executive function decline in Parkinson's disease.

BACKGROUND: Pathologic perivascular spaces (PVS), the fluid-filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinson's disease (PD). However, whether this impacts specific cognitive domains has not been investigated. OBJECTIVES: This study examined the relationship of PVS volume at baseline with domain-specific and global cognitive change over 2 years in PD individuals. METHODS: A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years. RESULTS: Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores. CONCLUSIONS: While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains.

High-frequency repetitive transcranial magnetic stimulation ameliorates memory impairment by inhibiting neuroinflammation in the chronic cerebral hypoperfusion mice.

BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been found to ameliorate cognitive impairment. However, the effects of HF-rTMS remain unknown in chronic cerebral hypoperfusion (CCH). AIM: To investigate the effects of HF-rTMS on cognitive improvement and its potential mechanisms in CCH mice. MATERIALS AND METHODS: Daily HF-rTMS therapy was delivered after bilateral carotid stenosis (BCAS) and continued for 14 days. The mice were randomly assigned to three groups: the sham group, the model group, and the HF-rTMS group. The Y maze and the new object recognition test were used to assess cognitive function. The expressions of MAP-2, synapsis, Myelin basic protein(MBP), and brain-derived growth factors (BDNF) were analyzed by immunofluorescence staining and western blot to evaluate neuronal plasticity and white matter myelin regeneration. Nissl staining and the expression of caspase-3, Bax, and Bcl-2 were used to observe neuronal apoptosis. In addition, the activation of microglia and astrocytes were evaluated by fluorescence staining. The inflammation levels of IL-1ß, IL-6, and Tumor Necrosis Factor(TNF)-α were detected by qPCR in the hippocampus of mice in each group. RESULTS: Via behavioral tests, the BCAS mice showed reduced a rate of new object preference and decreased a rate of spontaneous alternations, while HF-rTMS significantly improved hippocampal learning and memory deficits. In addition, the mice in the model group showed decreased levels of MAP-2, synapsis, MBP, and BDNF, while HF-rTMS treatment reversed these effects. As expected, activated microglia and astrocytes increased in the model group, but HF-rTMS treatment suppressed these changes. HF-rTMS decreased BCAS-induced neuronal apoptosis and the expression of pro-apoptotic protein (Caspase-3 and Bax) and increased the expression of anti-apoptotic protein (Bcl-2). In addition, HF-rTMS inhibited the expression of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). CONCLUSIONS: HF-rTMS alleviates cognitive impairment in CCH mice by enhancing neuronal plasticity and inhibiting inflammation, thus serving as a potential method for vascular cognitive impairment.

CRY2 mediates the cognitive decline induced by sleep deprivation in 5xFAD mice.

BACKGROUND: Cryptochrome-2 (CRY2) is a core rhythm gene that plays a crucial role in DNA damage repair. The present study investigated the potential role of CRY2 in mediating sleep deprivation-induced cognitive decline in 5xFAD mice. METHODS: To assess the effects of SD on different brain regions of the mouse brain, we used 18F FDG PET-CT. Cognitive function was evaluated using the Morris water maze test and Y-maze. Lentivirus was used for the overexpression of CRY2, and small interfering RNA (siRNA) was used for the downregulation of CRY2 to verify the effect of CRY2. We used qRT‒PCR and Western blotting to identify the downstream factors of CRY2 and evaluated the cognitive function of mice to confirm the effects of these factors. RESULTS: The AD mice exhibited cognitive decline after 21 days of SD and had higher expression of CRY2 compared to AD mice with normal sleep. Overexpression of CRY2 led to decreased cognitive function in AD mice, and the downregulation of CRY2 attenuated the SD-induced cognitive decline in AD mice. CRY2 reduced the expression and function of CISH, which reduced the inhibition of STAT1 phosphorylation and led to synaptic dysfunction. CISH overexpression attenuated the impairing effect of sleep deprivation on cognitive function in AD mice. Furthermore, 18F FDG PET-CT revealed that SD significantly reduced glucose metabolism in different brain regions of AD mice. CONCLUSION: Our study demonstrated that sleep deprivation upregulated CRY2 in the hippocampus of AD mice, which resulted in synaptic dysfunction by decreasing CISH-mediated STAT1 phosphorylation.

Resting-state neural activity and cerebral blood flow alterations in type 2 diabetes mellitus: Insights from hippocampal subfields.

OBJECTIVE: In this study, multimodal magnetic resonance imaging (MRI) imaging was used to deeply analyze the changes of hippocampal subfields perfusion and function in patients with type 2 diabetes mellitus (T2DM), aiming to provide image basis for the diagnosis of hippocampal-related nerve injury in patients with T2DM. METHODS: We recruited 35 patients with T2DM and 40 healthy control subjects (HCs). They underwent resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) scans, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, and regional homogeneity (ReHo) value of the bilateral hippocampus subfields. RESULTS: The CBF values of cornu ammonis area 1 (CA1), dentate gyrus (DG), and subiculum in the right hippocampus of T2DM group were significantly lower than those of HCs. The ALFF values of left hippocampal CA3, subiculum, and bilateral hippocampus amygdala transition area (HATA) were higher than those of HCs in T2DM group. The ReHo values of CA3, DG, subiculum, and HATA in the left hippocampus of T2DM group were higher than those of HCs. In the T2DM group, HbAc1 and FINS were negatively correlated with imaging characteristics in some hippocampal subregions. CONCLUSION: This study indicates that T2DM patients had decreased perfusion in the CA1, DG, and subiculum of the right hippocampus, and the right hippocampus subiculum was associated with chronic hyperglycemia. Additionally, we observed an increase in spontaneous neural activity within the left hippocampal CA3, subiculum, and bilateral HATA regions, as well as an enhanced local neural coordination in the left hippocampal CA3, DG, HATA, and subiculum among patients with type 2 diabetes, which may reflect an adaptive compensation for cognitive decline. However, this compensation may decline with the exacerbation of metabolic disorders.

Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice.

Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms are unclear. We used optogenetic and chemogenetic tools to identify the crucial roles of the hippocampal CA1 astrocytes in cognitive decline. Our results showed that repeated optogenetic stimulation of the hippocampal CA1 astrocytes induced cognitive impairment in mice and decreased synaptic long-term potentiation (LTP), which was accompanied by the appearance of inflammatory astrocytes. Mechanistic studies conducted using knockout animal models and hippocampal neuronal cultures showed that lipocalin-2 (LCN2), derived from reactive astrocytes, mediated neuroinflammation and induced cognitive impairment by decreasing the LTP through the reduction of neuronal NMDA receptors. Sustained chemogenetic stimulation of hippocampal astrocytes provided similar results. Conversely, these phenomena were attenuated by a metabolic inhibitor of astrocytes. Fiber photometry using GCaMP revealed a high level of hippocampal astrocyte activation in the neuroinflammation model. Our findings suggest that reactive astrocytes in the hippocampus are sufficient and required to induce cognitive decline through LCN2 release and synaptic modulation. This abnormal glial-neuron interaction may contribute to the pathogenesis of cognitive disturbances in neuroinflammation-associated brain conditions.

The effects of moderate-intensity aerobic exercise on cognitive function in individuals with stroke-induced mild cognitive impairment: a randomized controlled pilot study.

OBJECTIVE: To assess the impact of moderate-intensity aerobic exercise on working memory in stroke-induced mild cognitive impairment (MCI). DESIGN: Randomized, double-blind controlled study. SUBJECTS AND METHODS: Twenty MCI patients from the Fifth Affiliated Hospital of Guangzhou Medical University (December 2021 to February 2023), aged 34-79, 2-12 months post-stroke, were divided into an experimental group (EG) and a control group (CG), each with 10 participants. The EG underwent standard rehabilitation plus 40 minutes of aerobic exercise, while the CG received only standard therapy, 5 times weekly for 2 weeks. Working memory was tested using the n-back task, and overall cognitive function was measured with the MOCA and MMSE Scales before and after the intervention. RESULTS: The EG showed higher 3-back correctness (71.80 ± 14.53 vs 56.50 ± 13.66), MOCA scores (27.30 ± 1.57 vs 24.00 ± 3.13), and improved visuospatial/executive (4.60 ± 0.52 vs 3.30 ± 1.06) and delayed recall (4.30 ± 0.82 vs 3.00 ± 1.56) on the MOCA scale compared with the CG. CONCLUSION: Moderate-intensity aerobic exercise may enhance working memory, visuospatial/executive, and delayed recall functions in stroke-induced MCI patients.