Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

Background: The number of individuals with mild cognitive impairment (MCI), or those people without dementia who are experiencing age-related cognitive decline, has increased in recent years. Conveniently, several interventions to delay cognitive decline exist, where cognitively stimulating activities (CSA) have been receiving too much attention. However, its beneficial effects have not been well established among older people with MCI due to conflicting findings. Objectives: This study aimed to assess and summarize the available evidence on the effects of CSA on the overall cognitive functioning of older people with MCI. Specifically, it sought to answer the PICO question, “In older people with MCI, does engagement in cognitively stimulating activities improve cognitive function?” Methods: A systematic review and meta-analysis of randomized controlled trials examining the effects of CSA on older people with MCI were conducted. Three studies met the inclusion criteria from the 1,328 records from BioMed Central, CINAHL, Cochrane Library, Health Source: Nursing/Academic Edition, MEDLINE, and PubMed databases and 156 articles from WorldCat, DSpace Saint Louis University, and Google Scholar databases and catalogs. Effect size values were inspected using the random-effects model. Data were summarized as standardized mean difference (SMD) with corresponding 95% confidence intervals in the forest plot. Results: This meta-analysis which compared studies that employed similar methodologies, found that CSA has a significant, large effect in improving cognitive functioning among older people with MCI, evidenced by an SMD of 0.798 (95% CI = 0.510-1.085, p = 0.001). While its superiority over other interventions that improve cognitive function was not observed in this study, it was still found that using CSA was helpful in terms of its cost-effectiveness. Also, heterogeneity across studies was non-significant (Cochran’s Q = 0.151, df = 2, p = 0.927, I2 = 0.00%). These results mean that clinical heterogeneity was absent even though a diverse range of CSA was employed. Additionally, methodological diversity was not present since there were no variations in the study design and minimal variability in the risk of bias assessment. Conclusion Overall, it is acknowledged that CSA are effective and practical, inexpensive, non-pharmacologic cognitive training approaches to delay cognitive decline among older people with MCI. However, interpreting this study’s significant, large effect, and non-significant heterogeneity warrants caution.
Cognition ; Cognitive Dysfunction ; Meta-Analysis

BACKGROUND

Type 2 Diabetes Mellitus (T2DM) patients are predisposed to cognitive decline and dementia. The cooccurrence of the two diseases translate to a higher medical cost. Identification of factors contributing to cognitive impairment is warranted.

To determine the predictors of cognitive impairment among Filipino patients with Type 2 Diabetes Mellitus.

This is a cross-sectional analytical study involving Filipino patients diagnosed with T2DM in the outpatient clinic. A total of 171 patients were included and were screened using AD8-P tool.

A total of 171 adult patients were included and screened for cognitive impairment.19.3% were cognitively impaired, with mean age of 59.6 years old (vs. 55.5 years old, p < 0.029), and two-thirds were female. The mean duration of the patient’s diabetes was 11.2 years. After adjusting for confounders and multi-collinearity, the duration of diabetes was significantly associated with cognitive impairment with odds of developing cognitive impairment increasing as the duration reach 10 years above. Those with T2DM for at least ten years were 2.5 times more likely to develop cognitive impairment, holding the age constant. (OR = 2.5, 95% CI – 1.0 to 5.8, p < 0.043).

19.3% of Filipino patients with Type 2 Diabetes Mellitus in a tertiary government hospital are cognitively impaired and this can occur even in less than 65 years old. The ten years or longer duration of T2DM increases the risk of developing cognitive impairment by 2.5%.

BACKGROUND: Chronic illnesses such as Type 2 diabetes mellitus (T2DM) and obesity have been implicated as risk factors in the development of cognitive impairment (CI), but despite this, definite association between the two conditions in increasing cognitive impairment risk is not well defined. OBJECTIVE: This study aims to examine the association between body mass index (BMI) and cognitive impairment (CI) in elderly patients with Type 2 diabetes mellitus. METHODS: This is a cross-sectional study conducted in the outpatient clinics of a private hospital in Manila which included elderly patients with Type 2 diabetes. BMI categories of the subjects were determined using the Asia-Pacific criteria and the Montreal Cognitive Assessment – Philippines (MOCA-P) was administered to subjects who fulfilled the inclusion criteria. Descriptive statistics were used to determine the prevalence of impaired cognition among subjects while risk ratio analysis was used to determine the correlation between BMI and CI. Correlation analysis and linear regression analysis were used to determine the presence of association between cognition (measured by MOCA-P scores) and BMI. For all analysis, a 95% level of significance was used. RESULTS: A total of 109 subjects from the outpatient clinics were included in the study. A high percentage of the study population (90.83%) had CI based on MOCA-P scores. Subjects that belonged to the extremes of BMI- underweight and obese class 2 had higher incidence of CI compared to the other groups. Underweight subjects had 1.103 (95% CI: 1.038 to 1.172) times likelihood of having impaired cognition (p-value 0.0016), while obese 2 subjects had 1.110 (95% CI: 1.040 to 1.184) times likelihood of having impaired cognition (p-value 0.0016). Regression analysis revealed that in subjects with diabetes of less than 10 years, cognition scores were negatively correlated to BMI (p-value 0.0454). Correlation analysis revealed that at the general population level, regardless of the external factors, increasing or decreasing BMI did not have significant effect on cognition scores. CONCLUSION Subjects who belonged to the extremes of BMI-underweight and obese class 2 – had higher incidence of CI compared to the other BMI groups. Among subjects with T2DM duration of less than 10 years, cognition scores tend to be negatively correlated to BMI.
diabetes mellitus, Type 2 ; cognitive impairment ; cognitive dysfunction ; Body Mass Index

Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies showed conflicting results regarding presence of cancer, cancer treatment, and its association with dementia. Likewise, depression is often associated with cognitive problems. Objectives: This study aims to determine the prevalence and association of cognitive impairment and depression among breast cancer patients Methods: This is a prospective cross-sectional study utilizing Montreal Cognitive Assessment – Philippines (MOCA-P) and Patient Health Questionnaire (PHQ-9) Filipino version questionnaires through face-to-face interview. In analyzing the presence of cognitive impairment and depression, Chi-square was performed; all significant factors from this test underwent binary logistic regression to ascertain the statistical effect size for the presence of cognitive impairment and depression. Results: Results showed that 80.8% (97 out of 120 patients) have cognitive impairment while 27.5% of the patients have depression. Among the patients with cognitive impairment, 24.2% of them had depression. Results also showed significant association between the level of education and MOCA-P score suggesting that the higher the level of education, the better the MOCA-P score. This study showed no significant association between presence of cognitive impairment and depression. Conclusion In analyzing and managing patients with cognitive impairment, the level of educational attainment should be put into consideration since it is correlated significantly with MOCA-P results. As such, concomitant depression should be addressed accordingly since it may affect the patients’ overall health status.
Cognitive Dysfunction ; Depression ; Breast Neoplasms ; Mental Status and Dementia Tests

INTRODUCTION: This study aimed to elucidate the cognitive profile of patients with mild cognitive impairment with Lewy bodies (MCI-LB) and to compare it to that of patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD). METHODS: Subjects older than 60 years with probable MCI-LB (n = 60) or MCI-AD (n = 60) were recruited. All patients were tested with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to assess their global cognitive profile. RESULTS: The MCI-AD and MCI-LB patients did not differ in total MMSE and MoCA scores. However, some sub-items in MMSE and MoCA were shown to be screening markers for differentiating MCI-LB from MCI-AD. In the visuoconstructive test, the total score and hands subitem score in the clock-drawing test were significantly lower in MCI-LB than in MCI-AD. As for the executive function, the 'animal fluency test', 'repeat digits backward test' and 'take paper by your right hand' in MMSE all showed lower scores in MCI-LB compared with MCI-AD. As for memory, 'velvet' and 'church' in MoCA and 'ball' and 'national flag' in MMSE had lower scores in MCI-AD than in MCI-LB. CONCLUSION This study presents the cognitive profile of patients with MCI-LB. In line with the literature on Dementia with Lewy bodies, our results showed lower performance on tests for visuoconstructive and executive function, whereas memory remained relatively spared in the early period.
Humans ; Cognitive Dysfunction ; Alzheimer Disease/diagnosis* ; Neuropsychological Tests ; Cognition

OBJECTIVE: To observe the effects of moxibustion at Yongquan（KI 1） on the cognitive function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency. METHODS: Eighty-four patients with post-stroke cognitive impairment of kidney essence deficiency were randomly divided into an observation group（42 cases，1 case dropped off）and a control group（42 cases，1 case dropped off）.The control group was treated with medication，electroacupuncture，rehabilitation training and repetitive transcranial magnetic stimulation（rTMS）；on the basis of the treatment as the control group，moxibustion at bilateral Yongquan（KI 1）was adopted in the observation group.Both groups were treated once a day，5 days a week with 2-day interval，4 weeks were required. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, Fugl-Meyer assessment-lower extremity (FMA-LE) score, Berg balance scale (BBS) score, functional independence measure (FIM) score, modified fall efficacy scale (MFES) score and scale for the differentiation of syndromes of vascular dementia (SDSVD) score before and after treatment were observed in the two groups. RESULTS: After treatment，the MoCA, MMSE, FMA-LE, BBS, FIM and MFES scores were higher than those before treatment in both groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment，the SDSVD scores were lower than those before treatment in both groups (P< 0.05), and the SDSVD score in the observation group was lower than that in the control group (P< 0.05). CONCLUSION Moxibustion at Yongquan（KI 1） can improve the cognitive function and motor and balance function of lower limbs in patients with post-stroke cognitive impairment of kidney essence deficiency，reduce the risk of fall and improve the quality of life.
Humans ; Cognition ; Cognitive Dysfunction/therapy* ; Dementia, Vascular ; Kidney ; Lower Extremity ; Moxibustion ; Quality of Life ; Stroke/complications*

OBJECTIVE: To observe the clinical efficacy of acupuncture of revised acupoint combination around the skull base in treating post-stroke mild cognitive impairment (PSMCI), and preliminary explore its action mechanism. METHODS: A total of 76 PSMCI patients were randomly divided into an observation group (38 cases, 4 cases dropped off) and a control group (38 cases, 3 cases dropped off, 1 case was removed). In the observation group, acupuncture of revised acupoint combination around the skull base (bilateral Fengchi [GB 20], Wangu [GB 12], Tianzhu [BL 10] and Yamen [GV 15], Baihui [GV 20]) was used for treatment. In the control group, 8 non-meridian and non-acupoint points at the distal end were selected for shallow puncture treatment. Retaining the needles of 30 min, once every other day,3 times a week for 4 weeks in both groups. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Barthel index (BI) and serum levels of cystatin C (Cys-C) and homocysteine (Hcy) were compared in the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the scores of MoCA were increased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was higher than that in the control group (P<0.05). The scores of MMSE and BI were increased compared with those before treatment in the observation group (P<0.05), and the score of MMSE in the observation group was higher than that in the control group (P<0.05). After treatment, the serum levels of Cys-C and Hcy were decreased compared with those before treatment in the observation group (P<0.05), and lower than those in the control group (P<0.05). After treatment, the serum level of Cys-C was increased compared with that before treatment in the control group (P<0.05). The total effective rate of the observation group was 88.2% (30/34), which was higher than 32.4% (11/34) of the control group (P<0.05). CONCLUSION Acupuncture of revised acupoint combination around the skull base can improve cognitive function and daily living ability of PSMCI patients, which may be related to the down regulation of serum levels of Cys-C and Hcy.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Cognitive Dysfunction/therapy* ; Stroke/complications* ; Treatment Outcome ; Skull Base

OBJECTIVES: To compare the efficacy of needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training in the treatment of post-stroke cognitive impairment (PSCI). METHODS: A total of 206 patients with PSCI were randomized into a needle retaining group (103 cases, 9 cases dropped out) and an electroacupuncture group (103 cases, 6 cases dropped out). In addition to the conventional basic medical treatment and the rehabilitation treatment, in the needle retaining group, electroacupuncture at Shenting (GV 24) and Baihui (GV 20) was applied, with continuous wave of 50 Hz in the first 15 min and with disperse-dense wave of 2 Hz/50 Hz in the last 15 min, the needles were continuously retained for 1 h after electroacupuncture, during which cognitive training was adopted; in the electroacupuncture group, cognitive training was performed after the same electric stimulation exerted for 30 min, without additional needles retaining. The treatment was given once a day, 5 times a week for totally 8 weeks in the two groups. Before and after 8-week treatment, the TCM syndrome score was observed; before and after 4,8-week treatment, the scores of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and ability of daily living were observed in the two groups. The clinical efficacy of the two groups was evaluated after 8-week treatment. RESULTS: After 8-week treatment, the TCM syndrome scores were increased compared with those before treatment in both groups (P<0.05); the TCM syndrome score in the needle retaining group was higher than that in the electroacupuncture group (P<0.05).After 4,8-week treatment, the scores of MMSE, MoCA and ability of daily living were increased compared with those before treatment in both groups (P<0.05); MMSE, MoCA scores after 4,8-week treatment and ability of daily living score after 8-week treatment in the needle retaining group were higher than those in the electroacupuncture group (P<0.05). The total effective rate was 90.4% (85/94) in the needle retaining group, which was superior to 82.5% (80/97) in the electroacupuncture group (P<0.05). CONCLUSIONS Both needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training can effectively treat PSCI, improve the clinical symptom, cognitive function and ability of daily living in PSCI patients. Needle retaining after electroacupuncture combined with cognitive training has a better therapeutic effect.
Humans ; Electroacupuncture ; Acupuncture Therapy ; Cognitive Training ; Acupuncture Points ; Cognitive Dysfunction/therapy* ; Stroke/complications* ; Treatment Outcome

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.
Humans ; Electroacupuncture ; Acupuncture Therapy ; Acupuncture Points ; Diabetes Mellitus, Type 2/therapy* ; Glycated Hemoglobin ; Cognitive Dysfunction/therapy* ; Cholesterol ; gamma-Aminobutyric Acid