Current Alzheimer Research - Volume 22, Issue 4, 2025

Alzheimer’s Disease (AD) is the most prevalent progressive neurodegenerative disorder, leading to significant cognitive decline and dementia. Oxytocin (OXT), a peptide hormone synthesized in the hypothalamus, has emerged as a critical player in cognitive functioning. Notably, alterations in OXT levels have been reported in individuals with Alzheimer’s disease.

This systematic review aims to synthesize existing literature from databases such as PubMed, Scopus, and Web of Science, focusing on the therapeutic potential of OXT in AD treatment. Two independent individuals conducted the screening procedure for all articles.

Our screening revealed that studies investigating OXT therapy primarily involve animal models. These studies consistently demonstrate that, OXT administration mitigates various memory deficits in animal models of AD. These improvements are linked to mechanisms such as reduced microglial-driven inflammation and decreased amyloid-beta (Aβ) deposition, but changes in plaque load do not always correspond directly to cognitive improvement.

While these findings are promising and oxytocin could be a potential therapeutic candidate for AD, the evidence is limited to animal studies. There is a lack of robust human data, making it difficult to draw firm conclusions about oxytocin’s efficacy in people with AD. Ongoing and future clinical trials will be crucial to determine whether these preclinical benefits translate to humans.

Despite the limited number of studies examining the effects of OXT on AD and the inherent challenges in conducting such research, the available evidence from animal studies suggests promising results. These findings can serve as a valuable foundation for future human and complementary studies aimed at exploring oxytocin’s therapeutic potential in treating AD.

It is debatable whether demographic factors alter the relationship between serum lipid traits and cognitive function. Few data have examined the effects of non-traditional lipid metrics on the lipid-cognition relationship. We aim to test the generality of relationships between lipid traits and cognitive function in Chinese adults.

Data from 5,959 participants were obtained from the China Health and Retirement Longitudinal Study (2011–2020). The cognitive function was assessed via the Mini-Mental State Examination. Effects of traditional lipid metrics (Total Cholesterol, TC, Triglycerides, TG, Low-Density Lipoprotein, LDL, High-Density Lipoprotein, HDL) and non-traditional lipid metrics (TC/HDL, LDL/HDL) were analyzed. We employed mixed-effect models, Group-Based Trajectory Models (GBTM), and logistic regression to examine the associations between baseline serum lipid traits and cognitive function.

As continuous variables, higher TG levels were correlated with higher cognitive scores (P = 0.036), and similar patterns were found in TC/HDL (P < 0.01) and LDL/HDL (P < 0.01). In contrast, higher HDL levels were associated with lower cognitive scores. Similar trends were observed when lipid traits were analyzed as categorical quartiles, and grouped by gender and age. Non-traditional lipid metrics (LDL/HDL, TC/HDL) had higher contributions to the variation of cognitive scores than traditional lipid metrics (TC, TG, LDL, HDL).

Results of this study further supported the protective effect of TG and negative effect of HDL in elderly adults, though confounding factors like baseline cognitive heterogeneity warrant future investigation. Notably, non-traditional lipid ratios demonstrated stronger predictive value for cognitive variation than individual lipid metrics.

Our study provided evidence for the generality of a significant association between traditional/non-traditional lipid metrics and cognitive function in middle-aged and elderly adults. The factors that vary with genders and age groups do not appear to significantly alter the lipid-cognition relationship.

Chronic stress is a major global health issue linked to conditions such as anxiety, depression, and cognitive decline. In rodent studies, chronic immobilization stress (CIS) is commonly used to investigate the neuropsychological effects of prolonged stress, leading to behaviours such as anhedonia, anxiety, and depressive-like symptoms. An enriched environment (EE) provides physical, cognitive, and sensory stimulation, which promotes social interaction, supports brain development, and can enhance the effectiveness of pharmacological treatments, improving overall therapeutic outcomes. Metformin, commonly prescribed for type 2 diabetes, has antidiabetic effects and helps reduce oxidative stress, inflammation, and cell death in the brain, which may contribute to its neuroprotective properties. This study aims to evaluate the effectiveness of metformin, an enriched environment (EE), and its combination in alleviating anxiety and depression-like behaviours, memory impairments, and metabolic changes.

Rats were exposed to chronic immobilization stress (CIS) for 2 hours per day over a period of 10 days, followed by 14 days of treatment with metformin (200 mg/kg) and 6 hours of daily exposure to an enriched environment (EE). Behavioural tests, including the open field test (OFT), elevated plus maze (EPM), sucrose preference test (SPT), and novel object recognition test (NORT), were conducted. After completing the behavioural assessments, the animals were euthanized, and their plasma levels of corticosterone (CORT), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, triglycerides, and glucose were measured. Additionally, the concentration of brain-derived neurotrophic factor (BDNF) in the hippocampus was analysed.

Rats exposed to chronic immobilization stress (CIS) exhibited increased anxiety and depressive-like behaviours, as well as poor performance in the novel object recognition test (NORT). These behavioural changes were linked to elevated levels of plasma corticosterone (CORT), LDL, cholesterol, triglycerides, and glucose, along with decreased HDL levels and lower hippocampal BDNF. Treatment with metformin, an enriched environment (EE), or their combination alleviated these effects, improving exploratory behaviour, sucrose preference, and recognition memory and reducing anxiety-like behaviours. These benefits were accompanied by increased hippocampal BDNF expression, elevated plasma HDL, and reduced levels of CORT, LDL, cholesterol, triglycerides, and glucose.

The combination of metformin and an enriched environment completely restored cognitive impairment and metabolic alterations in chronic stress conditions. Metformin’s ability to improve energy metabolism and reduce oxidative stress could be further enhanced in an enriched environment, which promotes cognitive function and resilience to stress.

Therefore, evidence suggests that EE can positively influence the outcomes of the neuroprotective effects of metformin and present promising therapeutic approaches for mitigating stress-induced behavioural and biochemical alterations.

Given the role of inflammation in the development of both Alzheimer's disease (AD) and periodontal disease, it is plausible that periodontal disease may influence the progression of AD. Complete blood count (CBC) parameters may also serve as predictive indicators for this condition. This study investigated the predictive value of CBC parameters on the progression of AD in patients with periodontal disease.

Data from a prospective cohort study (n=90) with 6-month follow-up was analyzed. AD was assessed based on the Clinical Dementia Rating Scale. Records of C-reactive Protein (CRP) levels and CBC parameters measured within the 6 months preceding the participation date were evaluated. Cognitive assessments at the initial and 6^th-month follow-up were performed using the Standardized Mini-Mental Test (SMMT). All patients underwent clinical periodontal examination.

The difference in SMMT score change (∆SMMT) and platelet distribution width (PDW) value between groups with and without periodontitis was statistically notable (p<0.05). The presence of periodontitis was found to be significantly associated with age, ∆SMMT, and PDW values using the multivariate logistic regression model (p<0.05). Furthermore, having Stage II and Stage III AD, periodontitis, age factor, and mean platelet volume (MPV) value had a notable impact on ∆SMMT (p<0.05). These findings may indicate that systemic inflammation as reflected by complete blood count parameters (such as PDW and MPV) may play a predictive role in cognitive decline in Alzheimer's disease patients with periodontitis.

PDW and MPV levels may have a predictive significance in clarifying the association between periodontitis and AD progression.

The mechanisms underlying the relationship between obesity and cognitive function remain unclear, particularly among older adults, where reliable evidence is limited. This study aimed to explore whether the relationship between obesity and cognitive function is mediated by sleep quality and blood pressure (BP) in older Chinese adults.

We conducted an observational study using data from a cluster randomized controlled trial (RCT) with 5 follow-up periods involving older adults in rural China. The trial took place in Sichuan, China, from May 2021 to May 2023. Telephone Interview for Cognitive Status (TICS-10) was used to assess the participants’ cognitive function. Additionally, linear mixed-effects models and mediation analyses were performed.

The mean age of participants was 70.89, and 225 out of 506 participants were males. Weight, waist circumference (WC), and hip circumference (HC) were positively associated with cognitive function, while compared to normal/underweight participants, participants with overweight had a significant association with cognitive function. Sleep quality mediated the association between weight and cognitive function (β = 0.01, (95% CI: 0.00 to 0.01), P < 0.001), accounting for a mediating effect proportion of 4.04% (95% CI: 2.19% to 8.00%). Diastolic blood pressure (DBP) mediated the association between overweight (β = 0.02, (95% CI: 0.00 to 0.05), P < 0.001), HC (β = 0.01, (95% CI: 0.00 to 0.01), P = 0.02), and WC (β = 0.01, (95% CI: 0.00, 0.01), P <0.001) and cognitive function, explaining approximately 4.46% (95% CI: 0.41% to 12.00%), 7.16% (95% CI: 0.36%, 17.00%), and 9.60% (95% CI: 1.11%, 25.00%) mediating proportion of the total effect, respectively.

Our study highlights the potential mediating roles of sleep quality and DBP in the relationship between obesity and cognitive function. The findings contribute to understanding the obesity-cognition link in older adults, particularly in rural settings. However, limitations, such as self-reported sleep measures and unmeasured confounders, warrant caution. Further research is needed to clarify the underlying mechanisms and inform targeted interventions.

Our study demonstrates a significant positive association between weight, body mass index (BMI), HC, and WC and cognitive function in older adults. These findings suggest that maintaining a moderately high level of overweight may be protective against cognitive decline in this population. Additionally, the study also provides insights into optimizing cognitive function through factors, such as sleep and BP management.