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Special Issue "Mild Cognitive Impairment"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Neuroscience".

Deadline for manuscript submissions: closed (10 February 2019)

Special Issue Editors

Guest Editor
Prof. Hiroyuki Shimada

Department for Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Japan
Website | E-Mail
Interests: Cohort study of geriatric syndromes 2; Community - based intervention research in elderly people with mild cognitive impairment; Safety driving in the older adults with cognitive impairments; Clinical research of preventing falls in long - term care settings
Guest Editor
Prof. Hyuntae Park

Department of Health Care and Science, College of Health Science, Dong-A University, Korea
E-Mail
Interests: measurement and assessment of habitual physical activity and chronotype in geriatric epidemiological studies, and the development of senior-frendly information and communications technologies and comprehensive e-health assessment and program

Special Issue Information

Dear Colleagues,

The American Academy of Neurology updated its practice guidelines on mild cognitive impairment (MCI) in December 2017. The AAN concluded that: 1) MCI is common in older populations, and its prevalence increases with age and lower educational levels, 2) persons with MCI are at higher risk of progressing to dementia than age-matched controls, but 14.4%–55.6% of people diagnosed with MCI may return to neurologically intact, 3) no high-quality evidence exists to support pharmacologic treatments for MCI, and 4) clinicians should recommend regular exercise, discuss diagnosis, prognosis, long-term planning, the lack of effective medicine options (Level B), and they may recommend cognitive training and biomarker research to patients with MCI and families (Level C). The guideline panel also recommended the following research: 1) the use of consistent diagnostic criteria for MCI and dementia in clinical trials, to improve the ability to apply and combine results; 2) the inclusion of patient cohorts with specific biomarker data in treatment studies targeted at specific pathologies; 3) the use of outcome measures that are direct measures of clinically meaningful patient outcomes; and 4) study of early lifestyle and comorbidity modifications and the effects of such changes on the progression of MCI to different dementia subtypes. This Special Issue summarizes the recent understanding of diagnostic criteria for MCI and dementia, specific biomarker of MCI, outcomes in clinical trials, modifiable factor of reversion from MCI to cognitive normal, and update evidence of clinical trials in MCI.

Prof. Hiroyuki Shimada
Prof. Hyuntae Park
Guest Editors

Manuscript Submission Information

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Keywords

  • Mild cognitive impairment
  • diagnosis
  • outcome
  • Alzheimer’s disease
  • dementia
  • reversion
  • cognition
  • evidence
  • RCT

Published Papers (9 papers)

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Research

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Open AccessArticle
Clinical and Biomarker Characteristics According to Clinical Spectrum of Alzheimer’s Disease (AD) in the Validation Cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD
J. Clin. Med. 2019, 8(3), 341; https://doi.org/10.3390/jcm8030341
Received: 20 January 2019 / Revised: 4 March 2019 / Accepted: 7 March 2019 / Published: 11 March 2019
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Abstract
We aimed to present the study design of an independent validation cohort from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (AD) (KBASE-V) and to investigate the baseline characteristics of the participants according to the AD clinical [...] Read more.
We aimed to present the study design of an independent validation cohort from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (AD) (KBASE-V) and to investigate the baseline characteristics of the participants according to the AD clinical spectrum. We recruited 71 cognitively normal (CN) participants, 96 with subjective cognitive decline (SCD), 72 with mild cognitive impairment (MCI), and 56 with AD dementia (ADD). The participants are followed for three years. The Consortium to Establish a Registry for AD scores was significantly different between all of the groups. The logical memory delayed recall scores were significantly different between all groups, except between the MCI and ADD groups. The Mini-Mental State Examination score, hippocampal volume, and cerebrospinal fluid (CSF) amyloid-β42 level were significant difference among the SCD, MCI, and ADD groups. The frequencies of participants with amyloid pathology according to PET or CSF studies were 8.9%, 25.6%, 48.3%, and 90.0% in the CN, SCD, MCI, and ADD groups, respectively. According to ATN classification, A+/T+/N+ or A+/T+/N− was observed in 0%, 15.5%, 31.0%, and 78.3% in the CN, SCD, MCI, and ADD groups, respectively. The KBASE-V showed a clear difference according to the AD clinical spectrum in neuropsychological tests and AD biomarkers. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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Open AccessArticle
Driving Cessation and Cognitive Dysfunction in Patients with Mild Cognitive Impairment
J. Clin. Med. 2018, 7(12), 545; https://doi.org/10.3390/jcm7120545
Received: 21 November 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
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Abstract
Although driving by adults with cognitive impairment is an important public health concern, little is known about the indicators of driving cessation in patients with mild cognitive impairment (MCI). We aimed to investigate the prevalence of driving cessation in patients with MCI and [...] Read more.
Although driving by adults with cognitive impairment is an important public health concern, little is known about the indicators of driving cessation in patients with mild cognitive impairment (MCI). We aimed to investigate the prevalence of driving cessation in patients with MCI and the predictive value of cognitive performances for driving cessation. Patients with MCI were recruited in the Seoul National University Bundang Hospital; they met following inclusion criteria. Age range of 51–80 years, Clinical Dementia Rating scale score of 0.5, and ever car drivers including former and current drivers. All participants underwent comprehensive standardized cognitive assessments and information on driving status was obtained via an interview using a systematic questionnaire. The median age of the 135 participants was 72 years, and 54 participants (40%) were women; 93 patients (68.9%) were current drivers and 42 (31.1%) were former drivers. In univariate analysis, former drivers showed poorer performances in digit span backward and categorical fluency tests than current drivers. In multivariate logistic regression analysis, a poor digit span backward test score was significantly related with driving cessation (odds ratio: 0.493, 95% confidence interval: 0.258–0.939). In patients with MCI, poor performance in the digit span backward test, which represents impaired working memory capacity, was associated with a higher probability of driving cessation. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
Open AccessArticle
Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function
J. Clin. Med. 2018, 7(11), 413; https://doi.org/10.3390/jcm7110413
Received: 10 October 2018 / Revised: 24 October 2018 / Accepted: 1 November 2018 / Published: 4 November 2018
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Abstract
Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and [...] Read more.
Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and 82 without Alzheimer’s disease). Insulin resistance, regional gray matter volume, and cognitive function were assessed. A hierarchical moderated multiple regression (MMR) model was used to determine any associations among insulin resistance, structural changes in the brain, and cognitive decline. Results: The volumes of 7 regions in the gray matter were negatively related to insulin resistance in Alzheimer’s disease (p =0.032). Hierarchical MMR analysis indicated that insulin resistance did not directly affect the cognitive decline but moderated the cognitive decline through the decrease in gray matter volume in the key brain regions, i.e., inferior orbitofrontal gyrus (left), middle cingulate gyrus (right), hippocampus (right), and precuneus (right) (p < 0.05 in each case). Conclusion: Insulin resistance appears to exacerbate the cognitive decline associated with several gray matter volume loss. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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Open AccessArticle
Calf Circumference as a Screening Tool for Cognitive Frailty in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study (KFACS)
J. Clin. Med. 2018, 7(10), 332; https://doi.org/10.3390/jcm7100332
Received: 30 August 2018 / Revised: 3 October 2018 / Accepted: 4 October 2018 / Published: 8 October 2018
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Abstract
The aim of this study was to examine calf circumference in relation to cognitive frailty in community-dwelling older adults. Cross-sectional analysis was performed on the first-year baseline data of 1559 adults aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study. [...] Read more.
The aim of this study was to examine calf circumference in relation to cognitive frailty in community-dwelling older adults. Cross-sectional analysis was performed on the first-year baseline data of 1559 adults aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study. The final analysis included 1221 adults who were non-dependent in terms of instrumental activities of daily living, who underwent frailty and cognitive function assessments. Physical frailty was defined using the Fried Frailty Index. Cognitive impairment was defined as a score 1.5 standard deviations below the age-, sex- and education-matched norms on any of four cognitive-function tests. The prevalence of cognitive frailty was 2.8% for men and 3.8% for women. After adjusting for potential confounders, in comparison to the “physically robust without cognitive impairment” group, the estimates of increased odds ratios (ORs) for low calf circumference (<32 cm) were much greater in the prefrail with cognitive impairment (OR 4.62, 95% confidence interval (CI): 2.02–10.61) and frail with cognitive impairment (OR 10.94, 95% CI: 2.87–41.68) groups in men but not in women. Low calf circumference was strongly related to cognitive frailty in men only, suggesting calf circumference can be used as an indicator of these outcomes. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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Open AccessArticle
Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Induced Early Alzheimer’s Disease
J. Clin. Med. 2018, 7(10), 329; https://doi.org/10.3390/jcm7100329
Received: 21 August 2018 / Revised: 28 September 2018 / Accepted: 2 October 2018 / Published: 5 October 2018
Cited by 4 | PDF Full-text (3399 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. Here, we aimed to determine whether reactive oxygen species (ROS) reduction by [...] Read more.
Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. Here, we aimed to determine whether reactive oxygen species (ROS) reduction by resveratrol in the brain leads to cognitive impairment reduction in rats with angiotensin II (Ang-II)-induced early AD. Male Wistar Kyoto (WKY) rats with Ang-II-induced AD were treated with losartan or resveratrol for two weeks. Our results show decreased blood pressure, increased hippocampal brain-derived neurotrophic factor (BDNF) level, and decreased nucleus tractus solitarius (NTS) ROS production in the Ang-II groups with losartan (10 mg/kg), or resveratrol (10 mg/kg/day) treatment. Furthermore, losartan inhibition of hippocampal TauT231 phosphorylation activated AktS473 phosphorylation, and significantly abolished Ang-II-induced Aβ precursors, active caspase 3, and glycogen synthase kinase 3β (GSK-3β)Y216 expressions. Consistently, resveratrol showed similar effects compared to losartan. Both losartan and resveratrol restored hippocampal-dependent contextual memory by NADPH oxidase 2 (NOX2) deletion and superoxide dismutase 2 (SOD2) elevation. Our results suggest that both losartan and resveratrol exert neuroprotective effects against memory impairment and hippocampal damage by oxidative stress reduction in early stage AD rat model. These novel findings indicate that resveratrol may represent a pharmacological option similar to losartan for patients with hypertension at risk of AD during old age. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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Open AccessArticle
Cognitive Frailty Predicts Incident Dementia among Community-Dwelling Older People
J. Clin. Med. 2018, 7(9), 250; https://doi.org/10.3390/jcm7090250
Received: 28 July 2018 / Revised: 15 August 2018 / Accepted: 28 August 2018 / Published: 30 August 2018
Cited by 3 | PDF Full-text (623 KB) | HTML Full-text | XML Full-text
Abstract
Cognitive frailty, defined as the presence of both frailty and cognitive impairment, is a risk factor for adverse events in older adults. However, prevalence rates of cognitive frailty are low (1.1–2.5%), so primary screening is unsuitable in community settings. The aim of the [...] Read more.
Cognitive frailty, defined as the presence of both frailty and cognitive impairment, is a risk factor for adverse events in older adults. However, prevalence rates of cognitive frailty are low (1.1–2.5%), so primary screening is unsuitable in community settings. The aim of the study was to examine whether a new definition of cognitive frailty, which was developed for primary screening, is useful to predict incident dementia in community-dwelling older adults. A total of 4570 older adults participated in the study (2326 women; average age, 71.9 ± 5.5 years). We defined physical frailty as the presence of ≥1 of the following symptoms: slow walking speed and muscle weakness. Cognitive impairment was defined as ≥1 symptom of cognitive impairment, indicated by an age- and education-adjusted score that was ≥1.5 standard deviations below the reference threshold in word list memory, attention, executive function, and processing speed tests. Cognitive frailty was defined as comorbid physical frailty and cognitive impairment. The incidence of dementia was determined using data collected by the Japanese Health Insurance System over 36 months. The prevalence rates of physical frailty, cognitive impairment, and cognitive frailty were 17.5%, 15.3%, and 9.8%, respectively. Cognitive impairment (hazard ratio [HR]: 2.06, 95% confidence interval [95% CI]: 1.41–3.02) and cognitive frailty (HR: 3.43, 95% CI: 2.37–4.97) were found to be significant risk factors for dementia. However, the association between dementia and physical frailty was not significant (HR: 1.13, 95% CI: 0.76–1.69). Individuals with comorbid physical frailty and cognitive impairment could have a higher risk of dementia than healthy older adults or older adults with either physical frailty or cognitive impairment alone. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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Open AccessArticle
Physical Frailty and Amyloid-β Deposits in the Brains of Older Adults with Cognitive Frailty
J. Clin. Med. 2018, 7(7), 169; https://doi.org/10.3390/jcm7070169
Received: 9 May 2018 / Revised: 22 June 2018 / Accepted: 6 July 2018 / Published: 9 July 2018
Cited by 2 | PDF Full-text (4976 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Background: Cognitive frailty and impairment are phenotypically and pathophysiologically correlated with physical frailty. We examined associations between accumulation of amyloid-β in the brain as a brain imaging biomarker and phenotypes of physical frailty (weight loss, weakness, exhaustion, slowness, low physical activity) in older [...] Read more.
Background: Cognitive frailty and impairment are phenotypically and pathophysiologically correlated with physical frailty. We examined associations between accumulation of amyloid-β in the brain as a brain imaging biomarker and phenotypes of physical frailty (weight loss, weakness, exhaustion, slowness, low physical activity) in older adults with mild cognitive impairment (MCI) and cognitive frailty. Methods: Cross-sectional associations between brain amyloid-β accumulation measured with 11C-Pittsburgh compound B (PiB)-positron emission tomography (PET) and physical frailty were examined in 48 elderly participants (mean age: 75.1 ± 6.6 years; 73% female). Cortical and regional standard uptake value ratios (SUVRs) were obtained. Main outcome measures included frailty phenotypes and physical functions (gait speed, short physical performance battery, and Timed Up and Go tests). Results: Mean cortical region of interest and regional SUVRs (frontal cortex, temporal cortex, parietal cortex, precuneus/posterior cingulate cortex (PC/PCC), hippocampus, basal ganglia, and global SUVR) were associated with gait speed, Timed Up and Go, and short physical performance battery (PC/PCC, basal ganglia). In addition, SUVRs of all brain regions were significantly linked to weakness. Conclusion: SUVRs of all brain regions revealed an association between brain amyloid-β accumulation and weakness. Furthermore, global SUVRs (frontal cortex, temporal cortex, parietal cortex, PC/PCC, hippocampus, basal ganglia) were associated with gait parameters. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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Open AccessArticle
Lower Limb Function in Elderly Korean Adults Is Related to Cognitive Function
J. Clin. Med. 2018, 7(5), 99; https://doi.org/10.3390/jcm7050099
Received: 6 April 2018 / Revised: 23 April 2018 / Accepted: 26 April 2018 / Published: 1 May 2018
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Abstract
Patients with cognitive impairment have decreased lower limb function. Therefore, we aimed to investigate the relationship between lower limb function and cognitive disorders to determine whether lower limb function can be screened to identify cognitive decline. Using Korean National Health Insurance Service-National Sample [...] Read more.
Patients with cognitive impairment have decreased lower limb function. Therefore, we aimed to investigate the relationship between lower limb function and cognitive disorders to determine whether lower limb function can be screened to identify cognitive decline. Using Korean National Health Insurance Service-National Sample Cohort database data, we assessed the cognitive and lower limb functioning of 66-year-olds who underwent national health screening between 2010 and 2014. Cognitive function was assessed via a questionnaire. Timed Up-and-Go (TUG) and one-leg-standing (OLS) tests were performed to evaluate lower limb function. Associations between cognitive and lower limb functions were analyzed, and optimal cut-off points for these tests to screen for cognitive decline, were determined. Cognitive function was significantly correlated with TUG interval (r = 0.414, p < 0.001) and OLS duration (r = −0.237, p < 0.001). Optimal cut-off points for screening cognitive disorders were >11 s and ≤12 s for TUG interval and OLS duration, respectively. Among 66-year-olds who underwent national health screening, a significant correlation between lower limb and cognitive function was demonstrated. The TUG and OLS tests are useful screening tools for cognitive disorders in elderly patients. A large-scale prospective cohort study should be conducted to investigate the causal relationship between cognitive and lower limb function. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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Review

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Open AccessReview
The Role of Irisin in Alzheimer’s Disease
J. Clin. Med. 2018, 7(11), 407; https://doi.org/10.3390/jcm7110407
Received: 3 October 2018 / Revised: 26 October 2018 / Accepted: 29 October 2018 / Published: 1 November 2018
Cited by 2 | PDF Full-text (633 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is characterized by progressive memory dysfunction, oxidative stress, and presence of senile plaques formed by amyloid beta (Aβ) accumulation in the brain. AD is one of the most important causes of morbidity and mortality worldwide. AD has a [...] Read more.
Alzheimer’s disease (AD) is characterized by progressive memory dysfunction, oxidative stress, and presence of senile plaques formed by amyloid beta (A β ) accumulation in the brain. AD is one of the most important causes of morbidity and mortality worldwide. AD has a variety of risk factors, including environmental factors, metabolic dysfunction, and genetic background. Recent research has highlighted the relationship between AD and systemic metabolic changes such as glucose and lipid imbalance and insulin resistance. Irisin, a myokine closely linked to exercise, has been associated with glucose metabolism, insulin sensitivity, and fat browning. Recent studies have suggested that irisin is involved in the process in central nervous system (CNS) such as neurogenesis and has reported the effects of irisin on AD as one of the neurodegenerative disease. Here, we review the roles of irisin with respect to AD and suggest that irisin highlight therapeutic important roles in AD. Thus, we propose that irisin could be a potential future target for ameliorating AD pathology and preventing AD onset. Full article
(This article belongs to the Special Issue Mild Cognitive Impairment)
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