Normal aging and to a greater degree degenerative brain diseases such as Alzheimer's disease (AD), cause changes in the brain's structure and function. Degenerative changes in brain structure and decline in its function are associated with declines in cognitive ability. Early detection of AD is a key priority in dementia services and research. However, depending on the disease progression, neurodegenerative manifestations, such as cerebral atrophy, are detected late in course of AD. Functional changes in the brain may be an indirect indicator of trans-synaptic activity and they usually appear prior to structural changes in AD. Resting-state functional magnetic resonance imaging (RS-fMRI) has recently been highlighted as a new technique for interrogating intrinsic functional connectivity networks. Among the majority of RS-fMRI studies, the default mode network (DMN), salience network (SN), and central executive network (CEN) gained particular focus because alterations to their functional connectivity were observed in subjects who had AD, who had mild cognitive impairment (MCI), or who were at high risk for AD. Herein, we present a review of the current research on changes in functional connectivity, as measured by RS-fMRI. We focus on the DMN, SN, and CEN to describe RS-fMRI results from three groups: normal healthy aging, MCI and AD.

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. The association of body mass index (BMI) and progression to Alzheimer's disease (AD) in MCI subjects according to age, sex, and cognitive intervention remains unknown. We investigated the relationship between BMI and the risk of progression to AD in subjects with MCI, as well as the effect of BMI on progression to AD depending on age, sex, cognitive intervention, and chronic diseases.Methods: Three hundred and eighty-eight MCI subjects were followed for 36.3 ± 18.4 months, prospectively. They underwent neuropsychological testing more than twice during the follow-up period. The MCI subjects were categorized into underweight, normal weight, overweight, and obese subgroups. The associations between baseline BMI and progression to AD over the follow-up period were estimated using Cox proportional hazard regression models. Data were analyzed after stratification by age, sex, cognitive intervention, and chronic diseases.Results: After adjustment for the covariates, the underweight MCI group had a higher risk of progression to AD [hazard ratio (HR): 2.38, 95% confidence interval (CI): 1.17–4.82] relative to the normal weight group. After stratifying by age, sex, cognitive intervention, and chronic diseases, this effect remained significant among females (HR: 3.15, 95% CI: 1.40–7.10), the older elderly ≥75 years old (HR: 3.52, 95% CI: 1.42–8.72), the non-intervention group (HR: 3.06, 95%CI: 1.18–7.91), and the hypertensive group (HR: 4.71, 95% CI: 1.17–18.99).Conclusion: These data indicate that underweight could be a useful marker for identifying individuals at increased risk for AD in MCI subjects. This association is even stronger in females, older elderly subjects, the non-cognitive intervention group, and the hypertensive group.

BackgroundAlthough several prior works reported that apathy is associated with conversion to Alzheimer’s disease in individuals with amnestic mild cognitive impairment (aMCI), effects of apathy on the functional connectivity (FC) of the brain remain unclear. In this study, we assessed the pattern of association between apathy and default mode network (DMN), salience network and central executive network (CEN) in aMCI subjects.MethodsFifty subjects with aMCI and 50 controls (CONs) participated in this study. They underwent clinical assessments and magnetic resonance imaging for the structural and resting-state scan. We explored the patterns of association between apathy inventory (IA) total score and the whole-brain voxel-wise FCs of the DMN, salience network and CEN in aMCI subjects.ResultsWe observed that the FCs of the DMN were less and those of CEN were more in the aMCI group than the CON group. Total IA score was negatively correlated with FCs of the anterior cingulate within the DMN, and positively correlated with FCs of the middle frontal, inferior frontal, and supramarginal gyrus within the CEN in the aMCI group.ConclusionOur findings suggest that distinctive patterns of association between apathy and FCs in the DMN and CEN in the aMCI group might reflect the putative role of functional network change in the development of apathy in aMCI.

ObjectivePrevious research has indicated that there are potential associations between education and total hippocampal volume in the trajectory of Alzheimer’s disease (AD). However, the correlation between education and hippocampal subfield volumes in the progression of AD has yet to be understood. This study examined the relationship between education, which is a standard proxy for cognitive reserve, and hippocampal subfield volumes in healthy and amnestic mild cognitive impairment (aMCI) groups.Subjects and methodsThirty-eight subjects with aMCI and 39 healthy control subjects underwent 3 T magnetic resonance imaging, and hippocampal subfield volumes were measured by automated segmentation. Multiple linear regression analysis was used to determine the association between education and hippocampal subfield volumes.ResultsEducation had a significant negative correlation with the left parasubiculum, presubiculum, and subiculum volumes in the aMCI group. In addition, multiple subfield volumes including left parasubiculum, left/right presubiculum, left cornus ammonis (CA)3, and left CA4 showed a significant correlation with the neuropsychological test scores in the control group and aMCI group.ConclusionThese findings contribute to a better understanding of the association between education, hippocampal subfield volumes, and amnestic cognitive functions in the early phase of AD.

ObjectiveThis study aimed to investigate thalamic shape alterations and their relationships with various episodic memory impairments in subjects with amnestic mild cognitive impairment (aMCI).MethodsWe compared volumes and morphological alterations of the thalamus between aMCI subjects and healthy controls. In addition, we investigated the correlation between thalamic deformations and various memory impairments in aMCI subjects using a comprehensive neuropsychological battery.ResultsThe normalized left thalamic volumes of the aMCI group were significantly smaller than those of the healthy control group (p<0.0001). aMCI subjects exhibited significant thalamic deformations in the left thalamic dorso-medial and antero-medial areas compared with healthy individuals. CERAD-K Word List Memory scores were significantly correlated with the left dorso-medial areas in aMCI subjects. There were no significant correlations between verbal fluency, Boston naming test, constructional praxis, Word List Recognition, and Visuospatial Recall scores and thalamic shape in aMCI subjects. Verbal delayed recall scores were also significantly correlated with the left dorso-medial areas in the aMCI group.ConclusionStructural alterations in the thalamic deformations in the left dorso-medial and antero-medial areas might be core underlying neurobiological mechanisms of thalamic dysfunction related to Word List Memory and delayed verbal recall in individuals with aMCI.

Objective South Korea is one of the countries with a very fast aging rate, and the prevalence of dementia is rapidly increasing. However, there are relatively few studies pertaining to sociodemographic and physical health-related factors associated with dementia knowledge and dementia worry.Methods This was a cross-sectional survey of a community in Seocho-gu, Seoul, Republic of Korea. Overall, 1,869 adults aged 60 years participated. Participants completed an online interview or face-to-face interview. Survey data comprised self-report questions including dementia knowledge, dementia worry, demographic, psychological, exercise, and cognitive activities. We conducted logistic regression analysis.Results There was a significant positive association between dementia worry and knowledge. Family history of dementia, education, income, sleep problems, depressed mood and loss of volition, chronic diseases, and presence of a past job were associated with dementia knowledge or worry. Reading, art, or social cognitive activities had a significant positive association with dementia knowledge, and writing or musical cognitive activities had a negative association with dementia worry.Conclusion We found that people with more dementia knowledge and less dementia worry engaged more in cognitive activities that could prevent dementia. Public education should be planned to improve dementia knowledge and reduce dementia worry.

Objective The risk of rapid cognitive decline in Alzheimer’s disease (AD) during the coronavirus disease 2019 (COVID-19) pandemic has been recognized. The purpose of this study was to investigate the cognitive decline in such patients during the COVID-19 pandemic by evaluating changes in their cognitive measure parameters before and after the pandemic.Methods This was a retrospective cohort study conducted in AD patients during their first visit and one-year regular follow-up for testing cognitive function at the Geriatric Psychiatry Clinic of Seoul St. Mary’s Hospital. Changes in the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Sum of Box for CDR (CDR-SB) scores were investigated. A time series analysis was performed to determine whether there was a significant difference in the MMSE, CDR, and CDR-SB scores of AD patients in pre- and post–COVID-19 periods.Results Overall, 130 AD patients aged 60 to 93 years were assessed. Their baseline mean MMSE score was 22.30 which had decreased to 21.08 at the one-year follow-up. Before November 2019, the average CDR differences for one year was 0.06, but after November 2019, it increased to 0.36 (p<0.001). Before November 2019, the average of the CDR-SB change value for one year was 1.69, but after November 2019, it increased to 3.00 (p<0.001). The difference in MMSE values for one year was not statistically significant. The time series analysis revealed a significant increase in the CDR and CDR-SB scores by approximately 0.47 (p=0.005) and 2.39 (p=0.002), before and after November 1, 2019, respectively.Conclusion This study revealed that the COVID-19 pandemic and social distancing worsen cognitive function in AD patients rapidly. Exposure to the COVID-19 pandemic and social distancing for at least seven months worsen cognitive decline significantly. Therefore, in order to minimize the adverse effects of the cognitive decline in these patients, the period of social distancing should be minimized.

ObjectiveCyanidin-3-glucoside (C3G), is a component of anthocyanin, have been considered to positively influence cognition and be beneficial for the prevention and treatment of dementia. We aimed to assess the safety and efficacy of cyanidin-3-glucoside-rich Oryza sativa L. (black rice) extract on cognitive function. MethodsA 12-weeks double-blind randomized, placebo controlled trial assessed safety and cognitive outcomes in participants with subjective memory impairment (n=48) following consumption of 6 black rice extract capsules or a placebo. Cognitive function was assessed using the ADAS-cog and the CERAD-K. Subjective memory impairment also assessed. Safety was assessed by hematologic blood test, urine analysis, and participant reports of adverse events. ResultsThere was significant improvement on subjective memory in intervention group. There was no statistically significant difference in objective cognitive outcomes following 12 weeks of consuming black rice extract. ADAS-cog scores, however, trended toward improvement in the intervention group compared to the placebo group. There was no adverse event. Conclusion Although significant improvement in objective cognitive function was not proved, we found that C3G-rich Oryza sativa L. extract improves subjective memory in this study. Therefore the results may be informative of the possible effectiveness of the C3G-rich Oryza sativa L. on cognitive function.