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  • 1
    Online Resource
    Online Resource
    Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer’s Disease: A Protocol for Multicenter Phase II Clinical Trial
    IOS Press ; 2023
    In:  Journal of Alzheimer's Disease Vol. 95, No. 3 ( 2023-09-26), p. 1263-1272
    Details
    In: Journal of Alzheimer's Disease, IOS Press, Vol. 95, No. 3 ( 2023-09-26), p. 1263-1272
    Abstract: Background: Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted. Objective: This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans. Methods: This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician’s interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aβ42/Aβ40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer’s Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT. Conclusions: This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD.
    Type of Medium: Online Resource
    ISSN: 1387-2877 , 1875-8908
    URL: Article
    DOI: 10.3233/JAD-230241
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2023
    detail.hit.zdb_id: 2070772-1
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  • 2
    Online Resource
    Online Resource
    Loss of association between plasma irisin levels and cognition in Alzheimer’s disease
    Elsevier BV ; 2022
    In:  Psychoneuroendocrinology Vol. 136 ( 2022-02), p. 105624-
    Details
    In: Psychoneuroendocrinology, Elsevier BV, Vol. 136 ( 2022-02), p. 105624-
    Type of Medium: Online Resource
    ISSN: 0306-4530
    URL: Article
    DOI: 10.1016/j.psyneuen.2021.105624
    RVK:
    YH 2600
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1500706-6
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  • 3
    Online Resource
    Online Resource
    Relationship Between Adipokines, Cognition, and Brain Structures in Old Age Depending on Obesity
    Oxford University Press (OUP) ; 2023
    In:  The Journals of Gerontology: Series A Vol. 78, No. 1 ( 2023-01-26), p. 120-128
    Details
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 78, No. 1 ( 2023-01-26), p. 120-128
    Abstract: Adipokines such as leptin and adiponectin are associated with cognitive function. Although adiposity crucially affects adipokine levels, it remains unclear whether the relationship between adipokines and cognition is influenced by obesity. Methods We enrolled 171 participants and divided them into participants with obesity and without obesity to explore the effect of obesity on the relationship between adipokines and cognition. In addition to plasma levels of leptin and adiponectin, multidomain cognitive functions and brain structures were assessed using neuropsychological testing and magnetic resonance imaging. Association between levels of these adipokines and Alzheimer’s disease (AD) was then assessed by logistic regression. Results We found that cognitive function was negatively associated with leptin levels and leptin-to-adiponectin ratio (LAR). Such correlations between leptin and cognitive domains were prominent in participants with obesity but were not observed in those without obesity. Leptin levels were associated with lower hippocampal volumes in participants with obesity. A significant interaction of leptin and obesity was found mostly in the medial temporal lobe. Both leptin and LAR were positively associated with insulin resistance and inflammation markers in all participants. Of note, LAR was associated with a higher risk of AD after adjusting for demographic variables, Apolipoprotein E genotype, and body mass index. Conclusions Obesity might be a factor that determines how adipokines affect brain structure and cognition. Leptin resistance might influence the relationship between adipokines and cognition. In addition, LAR rather than each adipokine levels alone may be a better indicator of AD risk in older adults with metabolic stress.
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    URL: Article
    DOI: 10.1093/gerona/glac021
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2043927-1
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Plasma amyloid-beta oligomer is related to subjective cognitive decline and brain amyloid status
    Springer Science and Business Media LLC ; 2022
    In:  Alzheimer's Research & Therapy Vol. 14, No. 1 ( 2022-11-03)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2022-11-03)
    Abstract: Subjective cognitive decline (SCD) is a target for Alzheimer’s disease prediction. Plasma amyloid-beta oligomer (AβO), the pathogenic form of Aβ in blood, has recently been proposed as a novel blood-based biomarker of AD prediction by representing brain Aβ deposition. The relationship between plasma AβO, brain Aβ deposition, and SCD in individuals with normal objective cognition has not been investigated. Methods In this cross-sectional study, we analyzed 126 participants with normal objective cognition. More SCD symptoms were expressed as higher scores of the Subjective Cognitive Decline Questionnaire (SCDQ) and Memory Age-associated Complaint Questionnaire (MACQ). The plasma AβO level of each participant was measured twice for validation and expressed as a concentration (ng/mL) and a ratio relative to the mean value of two internal standards. Brain Aβ deposition was assessed by [ 18 F] flutemetamol positron emission tomography (PET) and expressed as standard uptake value ratio (SUVR). Associations of SCDQ and MACQ with plasma AβO levels or SUVR were analyzed in multiple linear regression models. The association between plasma AβO level and flutemetamol PET positivity was assessed in logistic regression and receiver operative characteristic analyses. Results Overall, participants were 73.3 years old with female predominance (69.0%). After adjustment for confounders, high SCDQ and MACQ scores were associated with the high plasma AβO levels as both concentrations and ratios (ratios: standardized coefficient = 0.246 and p = 0.023 for SCDQ, standardized coefficient = 0.209 and p = 0.029 for MACQ; concentrations: standardized coefficient = 0.257 and p = 0.015 for SCDQ, standardized coefficient = 0.217 and p = 0.021 for MACQ). In contrast, SCDQ and MACQ were not significantly associated with SUVRs ( p = 0.134 for SCDQ, p = 0.079 for MACQ). High plasma AβO levels were associated with flutemetamol PET (+) with an area under the curve of 0.694 (ratio) or 0.662 (concentration). Combined with APOE e4, plasma AβO presented area under the curves of 0.789 (ratio) and 0.783 (concentration). Conclusions Our findings indicate that the high plasma AβO level could serve as a potential surrogate biomarker of severe SCD and the presence of brain Aβ deposition in individuals with normal objective cognition.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-022-01104-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2506521-X
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  • 5
    Online Resource
    Online Resource
    Plasma adiponectin levels predict cognitive decline and cortical thinning in mild cognitive impairment with beta-amyloid pathology
    Springer Science and Business Media LLC ; 2022
    In:  Alzheimer's Research & Therapy Vol. 14, No. 1 ( 2022-11-04)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2022-11-04)
    Abstract: Blood adiponectin and leptin are adipokines that emerged as potential biomarkers for predicting Alzheimer’s disease (AD) owing to their strong connection with obesity. Although obesity affects the relation between beta-amyloid (Aβ) aggregation and cognitive decline, the longitudinal interactive effect of adipokines and Aβ on cognition and brain structures in humans remains unexplored. Hence, we investigated whether plasma levels of adiponectin and leptin are associated with future cognitive decline and cortical thinning across Aβ conditions (Aβ [+] and Aβ [−] ) in individuals with mild cognitive impairment (MCI). Methods Of 156 participants with MCI from the longitudinal cohort study of Alzheimer’s Disease Neuroimaging Initiative (ADNI), 31 were Aβ (−) and 125 were Aβ (+) as determined by CSF analysis. The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores and the thickness of the parahippocampal and entorhinal cortices were used to evaluate cognition and brain structure, respectively. After stratifying groups by Aβ conditions, the association of cognitive and brain structural changes with baseline plasma levels of adiponectin and leptin was examined. Results Of the total 156 participants, 51 were women (32.7%). The mean age of participants was 74.5 (standard deviation 7.57), and the mean follow-up period was 54.3 months, without a difference between the Aβ (+) and (−) groups. After adjustment for confounders, higher plasma adiponectin levels were associated with a faster increase in ADAS-Cog scores, indicating faster cognitive decline under the Aβ (+) condition (beta = 0.224, p = 0.018). Likewise, participants with higher plasma adiponectin presented faster cortical thinning in the bilateral parahippocampal cortices under the Aβ (+) condition (beta = − 0.004, p = 0.012 for the right side; beta = − 0.004, p = 0.025 for the left side). Interestingly, plasma adiponectin levels were not associated with longitudinal ADAS-Cog scores or cortical thickness in the Aβ (−) condition. Plasma leptin levels were not predictive of cognition or cortical thickness regardless of Aβ status. Conclusion Plasma adiponectin can be a potential biomarker for predicting the speed of AD progression in individuals with Aβ (+) MCI.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-022-01107-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2506521-X
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  • 6
    Online Resource
    Online Resource
    Association of Plasma Creatine With Inflammation and Cognitive Function in Persons With and Without Alzheimer’s Disease
    Korean Association for Geriatric Psychiatry ; 2021
    In:  Korean Association for Geriatric Psychiatry Vol. 25, No. 2 ( 2021-10-30), p. 98-104
    Details
    In: Korean Association for Geriatric Psychiatry, Korean Association for Geriatric Psychiatry, Vol. 25, No. 2 ( 2021-10-30), p. 98-104
    Type of Medium: Online Resource
    ISSN: 1226-6329
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.47825/jkgp.2021.25.2.
    DOI: 10.47825/jkgp.
    DOI: 10.47825/jkgp.2021.25.2.98
    Language: Unknown
    Publisher: Korean Association for Geriatric Psychiatry
    Publication Date: 2021
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  • 7
    Online Resource
    Online Resource
    Association of metformin use with Alzheimer’s disease in patients with newly diagnosed type 2 diabetes: a population-based nested case–control study
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-12-15)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-12-15)
    Abstract: Metformin reduces insulin resistance, which constitutes a pathophysiological connection of diabetes with Alzheimer’s disease (AD), but the evidence of metformin on AD development was still insufficient and conflicting. We investigated AD risk in patients with newly diagnosed type 2 DM treated with metformin. This retrospective, observational, nested case–control study included patients with newly diagnosed type 2 DM obtained from the Korean National Health Insurance Service DM cohort (2002–2017). Among 70,499 dementia-free DM patients, 1675 AD cases were matched to 8375 controls for age, sex, and DM onset and duration. The association between AD and metformin was analyzed by multivariable regression analyses, adjusted for comorbidities and cardiometabolic risk profile. Metformin use was associated with an increased odds of AD (adjusted odds ratio [AOR] 1.50; 95% CI 1.23–1.83). The risk of AD was higher in patients with a longer DM duration. Furthermore, AD risk was significantly high in DM patients with depression (AOR 2.05; 95% CI 1.02–4.12). Given the large number of patients with DM who are taking metformin worldwide, a double-blinded, prospective study is required to determine the long-term cognitive safety of metformin.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-03406-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 8
    Online Resource
    Online Resource
    Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study
    Springer Science and Business Media LLC ; 2023
    In:  Alzheimer's Research & Therapy Vol. 15, No. 1 ( 2023-03-06)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-03-06)
    Abstract: Restless leg syndrome (RLS) is associated with poor sleep quality, depression or anxiety, poor dietary patterns, microvasculopathy, and hypoxia, all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia remains unclear. This retrospective cohort study aimed to explore the possibility that RLS could be deemed as a non-cognitive prodromal feature of dementia. Methods This was a retrospective cohort study using the Korean National Health Insurance Service-Elderly Cohort (aged ≥ 60). The subjects were observed for 12 years, from 2002 to 2013. Identifying patients with RLS and dementia was based on the 10th revised code of the International Classification of Diseases (ICD-10). We compared the risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) in 2501 subjects with newly diagnosed RLS and 9977 matched controls based on age, sex, and index date. The association between RLS and the risk of dementia was assessed using Cox regression hazard regression models. The effect of dopamine agonists on the risk of dementia among RLS patients was also explored. Results The baseline mean age was 73.4, and the subjects were predominantly females (63.4%). The incidence of all-cause dementia was higher in the RLS group than that in the control group (10.4% vs 6.2%). A baseline diagnosis of RLS was associated with an increased risk of incident all-cause dementia (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.24–1.72). The risk of developing VaD (aHR 1.81, 95% CI 1.30–2.53) was higher than that of AD (aHR 1.38, 95% CI 1.11–1.72). The use of dopamine agonists was not associated with the risk of subsequent dementia among patients with RLS (aHR 1.00, 95% CI 0.76–1.32). Conclusions This retrospective cohort study suggests that RLS is associated with an increased risk of incident all-cause dementia in older adults, providing some evidence that requires confirmation through prospective studies in the future. Awareness of cognitive decline in patients with RLS may have clinical implications for the early detection of dementia.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-023-01191-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2506521-X
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  • 9
    Online Resource
    Online Resource
    Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Neurology Vol. 100, No. 17 ( 2023-04-25), p. e1799-e1811
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 17 ( 2023-04-25), p. e1799-e1811
    Abstract: Previous studies have reported the protective effect of pioglitazone on dementia in patients with type 2 diabetes mellitus (DM). Recent studies have shown that pioglitazone also lowers the risk of primary and recurrent stroke. Understanding the characteristics of patients particularly associated with the benefits of pioglitazone would facilitate its personalized use by specifying subpopulations during routine clinical care. The aim of this study was to examine the effects of pioglitazone use on dementia in consideration of stroke occurrence. Methods Using nationwide longitudinal data of patients with DM from the Korean National Health Insurance Service DM cohort (2002–2017), we investigated the association of pioglitazone use with incident dementia in patients with new-onset type 2 DM. The heterogeneity of the treatment effect was examined using exploratory analyses. Using a multistate model, we assessed the extent to which incident stroke affects the association between pioglitazone use and dementia. Results Pioglitazone use was associated with a reduced risk of dementia, compared with nonuse (adjusted hazard ratio [aHR] = 0.84, 95% CI 0.75–0.95); the risk reduction in dementia was greater among patients with a history of ischemic heart disease or stroke before DM onset (aHR = 0.46, 95% CI 0.24–0.90; aHR = 0.57, 95% CI 0.38–0.86, respectively). The incidence of stroke was also reduced by pioglitazone use (aHR = 0.81, 95% CI 0.66–1.00). However, when the stroke developed during the observation period of pioglitazone use, such lowered risk of dementia was not observed (aHR = 1.27, 95% CI 0.80–2.04). Discussion Pioglitazone use is associated with a lower risk of dementia in patients with DM, particularly in those with a history of stroke or ischemic heart disease, suggesting the possibility of applying a personalized approach when choosing pioglitazone to suppress dementia in patients with DM.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000207069
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 10
    Online Resource
    Online Resource
    Video_2.MP4
    Frontiers Media SA ; 2023
    In:  Frontiers in Psychiatry Vol. 13 ( 2023-1-18)
    Details
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 13 ( 2023-1-18)
    Abstract: As the significance of the early diagnosis of mild cognitive impairment (MCI) has emerged, it is necessary to develop corresponding screening tools with high ecological validity and feasible biomarkers. Virtual reality (VR)-based cognitive assessment program, which is close to the daily life of the older adults, can be suitable screening tools for MCI with ecological validity and accessibility. Meanwhile, dehydroepiandrosterone (DHEA) has been observed at a low concentration in the older adults with dementia or cognitive decline, indicating its potential as a biomarker of MCI. This study aimed to determine the efficacy and usability of a VR cognitive assessment program and salivary DHEA for screening MCI. Methods The VR cognitive assessment program and the traditional Montreal Cognitive Assessment (MOCA) test were performed on 12 patients with MCI and 108 healthy older adults. The VR program operates in a situation of caring for a grandchild, and evaluates the memory, attention, visuospatial, and executive functions. An analysis of covariance (ANCOVA), a partial correlation analysis, and receiving operating characteristic (ROC) curve analysis were conducted for statistical analysis. Results According to the ANCOVA, no significant difference in MOCA scores was found between the normal and MCI groups ( F = 2.36, p = 0.127). However, the VR total score of the MCI group was significantly lower than that of the normal group ( F = 8.674, p = 0.004). There was a significant correlation between the MOCA and VR scores in the total and matched subdomain scores. The ROC curve analysis also showed a larger area under the curve (AUC) for the VR test (0.765) than for the MOCA test (0.598), and the sensitivity and specificity of the VR program were 0.833 and 0.722, respectively. Salivary DHEA was correlated with VR total ( R 2 = 0.082, p = 0.01) and attention scores ( R 2 = 0.086, p = 0.009). Conclusion The VR cognitive test was as effective as the traditional MOCA test in the MCI classification and safe enough for older adults to perform, indicating its potential as a diagnostic tool. It has also been shown that salivary DHEA can be used as a biomarker for MCI.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyt.2022.1057513
    DOI: 10.3389/fpsyt.2022.1057513.s001
    DOI: 10.3389/fpsyt.2022.1057513.s002
    DOI: 10.3389/fpsyt.2022.1057513.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564218-2
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