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Yen-Ni Hung,1 Zbigniew Kadziola,2 Alan JM Brnabic,3 Ju-Fen Yeh,4 Jong-Ling Fuh,5,6 Jen-Ping Hwang,7,8 William Montgomery,9 1School of Gerontology Health Management and Master Program in Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan, Republic of China; 2Real World Analytics, Eli Lilly GmbH, Vienna, Austria; 3Real World Analytics, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 4Department of Medicine, Eli Lilly and Company, Taiwan, Republic of China; 5Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, 6Faculty of Medicine, School of Medicine, National Yang Ming University, 7Department of Psychiatry, Taipei Veterans General Hospital, 8Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 9Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia Purpose: The objectives of this study were to estimate the incidence, cumulative incidence, and economic burden of Alzheimer’s disease (AD) in Taiwan, using data from the National Health Insurance Research Database (NHIRD).Materials and methods: This was a retrospective, longitudinal, observational study using data from the Longitudinal Health Insurance Database of the NHIRD. Patients were included in this study if they were 50 years of age or older and their records included a primary or secondary diagnosis of AD. New patients who met inclusion criteria were followed up longitudinally from 2005 to 2010. Costs were calculated for the first year following the diagnosis of AD.Results: Overall, a higher percentage of women than men were diagnosed with AD (54% vs 46%, respectively). The first AD diagnosis occurred most frequently in the age of 75–84 years. The person-year incidence rate increased from 5.63/1,000 persons (95% CI, 5.32–5.94) in 2005 to 8.17/1,000 persons (95% CI, 7.78–8.57) in 2010. The cumulative incidence rate was 33.54/1,000 persons (95% CI, 32.76–34.33) in 2005–2010. The total mean inflated annual costs per patient in new Taiwan dollars (NT$) in the first year of diagnosis ranged from NT$205,413 (2009) to NT$227,110 (2005), with hospitalization representing the largest component.Conclusion: AD represents a substantial burden in Taiwan, and based on the observed increase in incidence rate over time, it is likely that this burden will continue to increase. The findings reported here are consistent with previous research. The NHIRD contains extensive real-world information that can be used to conduct research, allowing us to expand our understanding of the incidence, prevalence, and burden of disease in Taiwan. Keywords: Alzheimer’s disease, incidence, medical costs, resource utilization

Chih-Wen Yang,1,2 Jong-Ling Fuh2,3 1Department of Neurology, National Yang-Ming University Hospital, Ilan, 2National Yang-Ming University School of Medicine, 3Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China Abstract: Exposure to anesthesia and surgery has been hypothesized to increase the risk of developing Alzheimer's disease (AD). While the exact pathogenesis of AD remains unknown, it potentially involves specific proteins (eg, amyloid beta and tau) and neuroinflammation. A growing body of preclinical evidence also suggests that anesthetic agents interact with the components that mediate AD neuropathology at multiple levels. However, it remains unclear whether anesthesia and surgery are associated with an increased risk of AD in humans. To date, there have not been randomized controlled trials to provide evidence for such a causal relationship. Besides, observational studies showed inconsistent results. A meta-analysis of 15 case–control studies revealed no statistically significant association between general anesthesia and the development of AD (pooled odds ratio [OR] =1.05; P=0.43). However, a few retrospective cohort studies have demonstrated that exposure to anesthesia and surgery is associated with an increased risk of AD. Thus, well-designed studies with longer follow-up periods are still needed to define the role of anesthesia in relation to the development of AD. Keywords: anesthesia, surgery, dementia, Alzheimer's disease

Idiopathic intracranial hypertension (IIH) is a rare disorder that typically affects obese women of childbearing age, but can also occur in paediatric populations. Patients usually present with diffuse, daily headache and visual disturbances, but either symptom can occur in isolation. Patients with IIH often have papilloedema; however, IIH without papilloedema is fairly common in patients with chronic daily headache. The pathogenesis of IIH is unknown; the high incidence of comorbid bilateral transverse sinus stenosis (BTSS) in patients with IIH suggests that the two conditions are linked, although no direct causal relationship has been established. Cerebrospinal fluid (CSF) pressure monitoring or lumbar puncture-which provides immediate symptomatic relief-are important in making a diagnosis of IIH. Current treatments for IIH include weight reduction, medical treatment, CSF diversion surgery, optic nerve sheath fenestration and, potentially, endovascular stenting (in patients with BTSS). Prevention of visual loss (which can be substantial) is the main goal of treatment. Residual headache and IIH recurrence are not uncommon after treatment, and regular follow-up is, therefore, warranted even in patients who achieve remission. This Review provides an update of current knowledge of the aetiology, pathophysiology and treatment of IIH. [ABSTRACT FROM AUTHOR]

Background: The caregiver burden on foreign paid caregivers (FPCs) is currently not well understood. This study identified predictors and differences in caregiver burden between FPCs and family caregivers who provided care for patients with dementia.Methods: We recruited 489 patients with dementia (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition) and used the Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR) Scale to assess their neuropsychiatric behavioral problems and severity of dementia. All caregivers [FPCs (n = 42) and family caregivers with (n = 42) and without (n = 447) FPCs] completed three questionnaires: the Zarit Burden Interview (ZBI), the Center for Epidemiological Studies-Depression Scale (CES-D), and caregivers' knowledge of dementia (KD). To understand caregiver burden, we analyzed the correlations between ZBI and other variables and investigated the differences between family caregivers and FPCs.Results: NPI and CDR scores were higher among patients assisted by FPCs than among those whose families did not employ FPCs. Burdens were greater among family caregivers assisted by FPCs than among FPCs and family caregivers who were not assisted by FPCs. Family caregivers had greater knowledge of dementia than did FPCs. For family caregivers, CES-D scores (Spearman's r = 0.650; p < 0.01) and patients' NPI scores (Spearman's r = 0.471; p < 0.01) were correlated with caregiver burden. For FPCs, only CES-D scores (Spearman's r = 0.511; p < 0.01) were correlated with caregiver burden. A linear regression model showed that CES-D scores contributed most to caregiver burden in all groups [β = 0.560 (family caregivers without FPCs), 0.546 (family caregivers with FPCs), and 0.583 (FPCs); p < 0.005].Conclusion: Both family caregivers and FPCs need emotional support. Adequate treatment to reduce the neuropsychiatric symptoms of patients with dementia might reduce the burden on family caregivers. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) are common in patients with dementia associated with Parkinson's disease (PDD). The relationship between cognition and NPS in PDD has not been well studied.Methods: Patients diagnosed with PDD were assessed for cognitive function and NPS. The instruments used were the Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and semantic verbal fluency according to the recommendation of the Movement Disorder Society Task Force.Results: We evaluated 127 PDD patients (76 males/51 females; mean age 77 ± 6.3 years). Their mean MMSE score was 17 ± 6.5 and the mean NPI score was 19 ± 20.4. The most prevalent NPI items were anxiety (57.5%), sleep problems (53.5%), and apathy (52.0%). Principal component factor analysis revealed that 12 items formed three factors, namely "mood and psychosis" (delusion, hallucination, agitation, depression, anxiety, apathy, and irritability), "vegetative" (sleep and appetite problems), and "frontal" (euphoria, disinhibition, and aberrant motor behavior). Symptoms of hallucination were significantly associated with MMSE score, even after controlling for the confounding variables.Conclusion: NPS are common and diverse among patients with PDD. Three specific subgroups of NPS were identified. Hallucination was significantly correlated with cognitive impairment, and could be a predictor of cognition in PDD patients. [ABSTRACT FROM AUTHOR]

Primary cough headache, primary exertional headache, primary sexual headache, and idiopathic stabbing headache are included in "Other Primary Headaches" (Group 4) in the International Classification of Headache Disorders, 2nd edition (ICHD-II). Headaches provoked by cough, exertion, and sex have different age distributions, but they do share some clinical and pathogenic characteristics. The triggering activities frequently involve Valsalva-like maneuvers, which may explain part of the pathogenesis. Primary stabbing headache is common and characterized by ultra-short stabbing headaches. All these headache disorders respond well to indomethacin, and they are commonly comorbid with migraine except for primary cough headache. Of note, some patients with sexual headache had reversible cerebral vasoconstriction syndromes. Recent large-scaled studies have revealed that the ICHD-II criteria of these four headache disorders cannot be completely fulfilled. Further revisions for the ICHD-II criteria are required based on these results of the evidence-based studies. [ABSTRACT FROM AUTHOR]

An abstract of and comment on the article "Cranial Autonomic Symptoms in Migraine: Headache Characteristics and Comparison with Cluster," by T.H. Lai and colleagues is presented.

Purpose: Both metabolic syndrome (MetS) and cognitive dysfunction impair health-related quality of life (HRQOL). This study aims to determine whether individuals experiencing both MetS and cognitive dysfunction have lower HRQOL., Methods: This cross-sectional study enrolled 567 participants who attended outpatient clinics at a medical center in northern Taiwan. MetS was diagnosed according to the modified criteria for the Asian population. Cognitive function was categorized as normal, mild cognitive dysfunction, and advanced cognitive dysfunction according to the score of the Montreal Cognitive Assessment, Taiwanese version. HRQOL was assessed using the SF-36v2® Health Survey (SF-36v2). The associations of the comorbidity status of MetS and cognitive dysfunction with HRQOL were analyzed using linear regression models, adjusting for age, sex, marital status, education level, income groups, and activities of daily living., Results: Out of 567 participants, 33 (5.8%) had MetS with mild cognitive dysfunction, and 34 (6.0%) had MetS with advanced cognitive dysfunction. Participants with both MetS and advanced cognitive dysfunction exhibited the lowest scores in the physical component summary and almost all scales of HRQOL. MetS exacerbated the inverse association between mild cognitive dysfunction and the mental component summary. For those with MetS, the scores on scales of role physical, bodily pain, vitality, and social functioning worsened as cognitive function deteriorated (all P trend <0.05)., Conclusion: As the severity of comorbidity between MetS and cognitive dysfunction varies, patients exhibited poorer performance in different aspects of HRQOL. Future research is needed to find solutions to improve HRQOL for patients with both MetS and cognitive dysfunction., Competing Interests: Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Research Ethics Committee of Taipei Veterans General Hospital, Taipei, Taiwan, on May 9, 2022 (Protocol Code: 2020-06-001 A). Consent to participate: All participants in this study provided written informed consent before participating in the research. Competing interests: The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aβ42/Aβ40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: To determine sex differences in clinical profiles and treatment outcomes in patients with spontaneous intracranial hypotension., Background: Spontaneous intracranial hypotension is associated with considerable functional disability and potentially fatal complications, and it is uncertain whether males and females should be managed differently., Methods: This was a cohort study of consecutive patients with spontaneous intracranial hypotension enrolled from a medical center. Medical records and imaging findings were reviewed. The outcome of treatment responses to epidural blood patches and risks of subdural hematoma were measured., Results: In total, 442 patients with spontaneous intracranial hypotension (165 males, 277 females) were included in the analysis. Males were more likely to have a delayed (>30 days) initial presentation than females (32.1% [53/165] vs. 19.9% [55/277], p = 0.004), and males were less likely to have nausea (55.8% [92/165] vs. 67.1% [186/277], p = 0.016), vomiting (43.0% [71/165] vs. 54.2% [150/277], p = 0.024), photophobia (9.7% [16/165] vs. 17.0% [47/277], p = 0.034), and tinnitus (26.7% [44/165] vs. 39.7% [110/277], p = 0.005) compared with females despite comparable radiologic findings. Among the 374 patients treated with epidural blood patches, males were more likely to be nonresponders to the first epidural blood patch (58.0% [80/138] vs. 39.0% [92/236], OR = 2.2, 95% CI = 1.4-3.3, p < 0.001). Males were at a higher risk of having subdural hematoma (29.7% [49/165] vs. 10.8% [30/277], OR = 3.5, 95% CI = 2.1-5.8, p < 0.001). Among patients with subdural hematoma, males had greater thickness (12.8 ± 4.3 vs. 8.1 ± 5.9 mm, p < 0.001) and were more likely to receive surgical drainage (55.1% [27/49] vs. 10.0% [3/30], OR = 11.0, 95% CI = 3.0-41.3, p < 0.001) than females., Conclusion: In the present study, spontaneous intracranial hypotension in males was characterized by a delayed presentation, poorer response to the first epidural blood patch, and a higher risk of subdural hematoma. Caution should be exercised in the management of males with spontaneous intracranial hypotension. The generalizability of the findings needs to be further confirmed., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Coronavirus disease 2019 (COVID-19) causes persistent symptoms, including brain fog. Based on limited research on the long-term consequences of mild COVID-19, which has yielded inconsistent results, we investigated which cognitive functions were most affected by COVID-19 in non-hospitalized Asian patients with long-term COVID and subjective cognitive complaints., Methods: Fifty-five non-hospitalized patients with long COVID and brain fog (24 males and 31 females, mean age: 45.6 ± 14.6 years, mean duration of education: 14.4 ± 3.0 years) were recruited. Neuropsychological assessments included screening tests for overall cognition, and comprehensive tests for memory, executive function, processing speed, and subjective emotional and disease symptoms. Cognitive test scores were converted into Z-scores. Moreover, principal component analysis (PCA) was employed to define cognitive domains across subtest scores., Results: Comprehensive assessments revealed cognitive impairment in 69.1% of patients (<1.5 standard deviation in at least one test). The processing speed (27.3%), memory recall (21.8%), memory learning (20.0%), and inhibitory control (18.2%) were the most affected areas. Self-reported anxiety and depression were observed in 35% and 33% of patients, respectively. Furthermore, the degree of self-anxiety can be used to predict learning performance., Conclusion: Nearly 70% of patients with subjective cognitive complaints and long COVID had objective cognitive impairments. A comprehensive evaluation is essential for patients with long COVID and brain fog, including those with mild symptoms., Competing Interests: Conflicts of interest: Dr. Jong-Ling Fuh, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF., Methods: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan. Clinical manifestations were retrieved from electronic medical records, and findings on ophthalmologic examination and magnetic resonance images (MRIs) were reviewed., Results: A total of 102 patients (71 F/31 M, mean age 33.4 ± 12.2 years, mean CSF pressure 282.5 ± 74.5 mm CSF) were identified, including 46 (45.1%) with obesity (body-mass index ≥ 27.5), and 57 (62.6%) with papilledema. Overall, 80 (78.4%), 55 (53.9%), 51 (50.0%), and 58 (56.9%) patients met the Second and Third Edition of International Classification of Headache Disorders, Friedman, and Korsbæk criteria, respectively. Patients in the 200-250 mm CSF group (n = 40) were less likely to have papilledema (48.5% vs. 70.7%, p = 0.035), transient visual obscuration (12.5% vs. 33.9%, p = 0.005), and horizontal diplopia (10.0% vs. 30.6%, p = 0.006), and had fewer signs on MRIs (2.2 ± 1.3 vs. 2.8 ± 1.0, p = 0.021) when compared with those with CSF pressures > 250 mm CSF (n = 62). However, the percentages of patients with headache (95.0% vs. 87.1%, p = 0.109) at baseline, chronic migraine at six months (31.6% vs. 25.0%, p = 0.578), and visual field defect (86.7% vs. 90.3%, p = 0.709) were similar., Conclusions: It was found that obesity and papilledema were less common in Asian IIH patients when compared with Caucasian patients. Although patients with CSF pressures of 200-250 mm CSF had a less severe phenotype, the risks of having headache or visual loss were comparable to those in the > 250 mm CSF group. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asians, although further studies are still needed., (© 2024. The Author(s).)

Aim: In Taiwan, over 90% of dementia patients received home care. Severe dementia-linked food refusal significantly affects nutrition, thereby straining caregivers. Family caregivers can reduce their burden by learning feeding and dementia nutrition online, thus preserving patient oral feeding. The study aim for family caregivers learn online Hand-Under-Hand (UH) techniques to ease feeding in severe dementia, enhancing nutrition and reducing their burden., Methods: In this quasi-experimental study, participants in the experimental group received 2-h UH courses online, while the control group received their usual care. The primary outcome indicators were abnormal eating behavior, nutritional status, and caregiver burden, with outcomes tracked at 0, 1, and 3 months. At the neurology outpatient clinic of a medical center in Taipei, 65 dyads-comprising patients with severe dementia and their caregivers-were randomly assigned to groups., Results: The study participants comprised 36 female and 29 male caregivers, with an average age of 58.09 years. The patient group included 43 females and 22 males, with a mean age of 83.32 years. Patients in the experimental group exhibited reduced abnormal eating behavior, and caregiver burden was reduced at 1 and 3 months, patients demonstrated improved nutritional status by month 3., Conclusions: The accessibility and convenience of online courses enabled family caregivers to use UH feeding techniques to effectively improve the nutritional status and correct the abnormal eating behavior of patients with dementia, while also decreasing caregiver burden. Geriatr Gerontol Int 2024; 24: 867-873., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Objective: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients., Methods: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS)., Results: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs., Conclusions: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Health-related quality of life (HRQoL) is an essential outcome parameter in geriatric research; however, the available evidence is mixed regarding the factors associated with HRQoL among people with dementia. We aimed to identify factors that contribute to HRQoL among people with dementia in residential long-term care (LTC) institutions., Methods: We randomly selected 299 of 1607 registered residential LTC institutions in Taiwan. A cross-sectional survey was conducted between 2019 and 2020, including items on demographic characteristics, comorbidities, the EuroQol-5 dimensions-5 levels (EQ-5D-5L; utility and visual analog scale [VAS] scores), the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), behavioral and psychological symptoms of dementia, activities of daily living (ADL), and instrumental ADL (IADL)., Results: In total, 1313 people with dementia from 267 institutions were enrolled (mean age, 76.4 ± 12.7 years). The mean EQ-5D-5L utility and VAS scores were 0.10 (standard deviation [SD] = 0.48) and 66.57 (SD = 20.67), respectively. In multivariate linear regression analysis, higher scores for ADL, IADL, and CDR sum of boxes were associated with higher utility scores. Higher VAS scores were associated with higher ADL and MMSE scores. Lower utility scores and VAS scores were associated with more frequent depressive symptoms., Conclusion: ADL, dementia severity, cognitive function, and depressive symptoms influenced the HRQoL of people with dementia in residential LTC institutions. Longitudinal studies should be conducted to better understand how HRQoL changes over time among people with disabilities., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral vasoconstriction. The pathophysiological mechanism of this mysterious syndrome remains underexplored and there is no clinically available molecular biomarker. To provide insight into the pathogenesis of RCVS, this study reported the first landscape of dysregulated proteome of cerebrospinal fluid (CSF) in patients with RCVS (n  =  21) compared to the age- and sex-matched controls (n  =  20) using data-independent acquisition mass spectrometry. Protein-protein interaction and functional enrichment analysis were employed to construct functional protein networks using the RCVS proteome. An RCVS-CSF proteome library resource of 1054 proteins was established, which illuminated large groups of upregulated proteins enriched in the brain and blood-brain barrier (BBB). Personalized RCVS-CSF proteomic profiles from 17 RCVS patients and 20 controls reveal proteomic changes involving the complement system, adhesion molecules, and extracellular matrix, which may contribute to the disruption of BBB and dysregulation of neurovascular units. Moreover, an additional validation cohort validated a panel of biomarker candidates and a two-protein signature predicted by machine learning model to discriminate RCVS patients from controls with an area under the curve of 0.997. This study reveals the first RCVS proteome and a potential pathogenetic mechanism of BBB and neurovascular unit dysfunction. It also nominates potential biomarker candidates that are mechanistically plausible for RCVS, which may offer potential diagnostic and therapeutic opportunities beyond the clinical manifestations., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates., Methods: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11)., Results: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher., Conclusions: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation., (© 2024. The Author(s).)

Background: The occurrence of cognitive impairment (CI) is expected to increase within an ageing population. CI is associated with tooth loss, which influences masticatory performance. A decrease in masticatory performance may cause functional and morphological changes in the brain. However, whether CI is associated with masticatory performance, demographics, and structural brain signatures has not been studied yet., Objectives: To assess the associations between CI on the one hand, and masticatory performance, demographic factors, and structural brain signatures (i.e. cortical volume and thickness) on the other hand., Methods: In total, 18 older adults with CI (mean ± SD age = 72.2 ± 9.5 years) and 68 older adults without CI (65.7 ± 7.5 years) were included in this study. Masticatory performance was quantified using a colour-changeable chewing gum. A Magnetic Resonance Imaging (MRI) scan was used to map structural brain signatures. To study our aim, a multivariate binary logistic regression analysis with backward selection was performed., Results: The cortical volume of the right entorhinal cortex was negatively associated with CI (p < .01). However, demographic factors, masticatory performance, and the other structural brain signatures under investigation were not associated with CI., Conclusion: A decrease in the volume of the right entorhinal cortex is associated with CI in older people., (© 2023 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Background: Swallowing problems are frequently seen in older adults, especially in individuals with cognitive impairment (CI). The brain plays a crucial role in both cognition and swallowing. Using magnetic resonance imaging (MRI) data, researchers identified regions associated with swallowing. However, it is not yet fully elucidated which factors influence the swallowing performance in older adults., Objectives: The current study investigated which factors, such as cognitive function, neuroanatomical factors (e.g., the cortical thickness and volume of specific brain regions) and demographical factors are associated with swallowing performance in older adults. Secondly, it was investigated whether there is a difference in neuroanatomical factors between individuals with and without CI., Research Design and Methods: In total, 15 CI individuals (73.1 ± 9.1 years; 46.7% male) and 48 non-CI controls (69.0 ± 5.1 years; 29.2% male) were included. The repetitive saliva swallowing test (RSST) was performed, and an MRI scan was acquired from the participants., Results: Multivariate linear regression analysis showed that the cortical thickness of the right supramarginal gyrus and female gender were positively associated, and a higher age was negatively associated with the RSST in older adults (p < .05). CI was not significantly associated with swallowing performance. Furthermore, it was found that the cortical volume differs more frequently between CI and non-CI than the cortical thickness., Conclusion: A thinner cortex of the right supramarginal gyrus and being an older female are associated with poorer swallowing performance. Secondly, cortical volume was more often found to differ between CI and non-CI individuals than cortical thickness., (© 2023 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Background: With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan., Methods: We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs., Results: The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items., Conclusion: Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families., Competing Interests: Conflicts of interest: Dr. Jong-Ling Fuh, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

The collection of head images for public datasets in the field of brain science has grown remarkably in recent years, underscoring the need for robust de-identification methods to adhere with privacy regulations. This paper elucidates a novel deep learning-based approach to deidentifying facial features in brain images using a generative adversarial network to synthesize new facial features and contours. We employed the precision of the three-dimensional U-Net model to detect specific features such as the ears, nose, mouth, and eyes. Results: Our method diverges from prior studies by highlighting partial regions of the head image rather than comprehensive full-head images. We trained and tested our model on a dataset comprising 490 cases from a publicly available head computed tomography image dataset and an additional 70 cases with head MR images. Integrated data proved advantageous, with promising results. The nose, mouth, and eye detection achieved 100% accuracy, while ear detection reached 85.03% in the training dataset. In the testing dataset, ear detection accuracy was 65.98%, and the validation dataset ear detection attained 100%. Analysis of pixel value histograms demonstrated varying degrees of similarity, as measured by the Structural Similarity Index (SSIM), between raw and generated features across different facial features. The proposed methodology, tailored for partial head image processing, is well suited for real-world imaging examination scenarios and holds potential for future clinical applications contributing to the advancement of research in de-identification technologies, thus fortifying privacy safeguards., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer's disease (AD). There is conflicting evidence regarding the association of peripheral TREM2 mRNA expression/soluble TREM2 (the extracellular domain of TREM2) with cognitive function/neuroinflammation in patients with AD. Herein, we studied the TREM2 and TREM2 alt mRNA expression and their association with the cognitive performance in subjects with mild dementia due to AD and healthy controls. In a subgroup of patients with AD, magnetic resonance spectroscopy was used to measure the myo-inositol level in the posterior cingulate cortex, a surrogate marker for neuroinflammation. The results showed that increased TREM2 and TREM2 alt mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and central neuroinflammation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

An increasing number of systematic reviews and meta-analyses have been published on the association between oral health and cognitive dysfunction, also known as oral-cognitive links. However, there is great diversity in the oral and cognitive factors included in these studies, with different opinions for clinical practice drawn from the evidence. To understand which oral and cognitive factors are involved in those associations, we conducted an umbrella review of 28 systematic reviews, including 12 meta-analyses, on oral-cognitive links. We found that (a) periodontal diseases, oral microbiome, and dementia were frequently studied, while other factors, such as mastication and mild cognitive impairment, were less commonly investigated, and (b) severe deterioration of oral health, such as severe periodontitis or extensive tooth loss, rather than the presence of oral diseases alone, was strongly associated with cognitive dysfunction. In conclusion, the diversity of oral and cognitive factors included in the review studies reflects the complexity of oral-cognitive links. Clarifying the factors helps to form evidence-based clinical advice for healthcare., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Half of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption., Methods: A cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption., Results: Forty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index., Conclusions: Dysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure., (© 2023. The Author(s).)

Objectives: To explore human glymphatic dynamics in a diseased model via a noninvasive technique., Methods: Patients with reversible vasoconstriction syndrome (RCVS) presenting with blood-brain barrier disruption, i.e., para-arterial gadolinium leakage on 3-T 3-dimensional isotropic contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2-FLAIR) magnetic resonance imaging (MRI), were prospectively enrolled. Consecutive 9-min-CE-T2-FLAIR for 5-6 times (early panel) after intravenous gadolinium-based contrast agent (GBCA) administration and one time-varying deferred scan of noncontrast T2-FLAIR (delayed panel) were performed. In Bundle 1, we measured the calibrated signal intensities (cSIs) of 10 different anatomical locations. In Bundle 2, brain-wide measurements of para-arterial glymphatic volumes, means, and medians of the signal intensities were conducted. We defined mean (mCoIs) or median (mnCoIs) concentration indices as products of volumes and signal intensities., Results: Eleven subjects were analyzed. The cSIs demonstrated early increase (9 min) in perineural spaces: (cranial nerve [CN] V, p = 0.008; CN VII + VII, p = 0.003), choroid plexus (p = 0.003), white matter (p = 0.004) and parasagittal dura (p = 0.004). The volumes, mCoIs, and mnCoIs demonstrated increasing rates of enhancement after 9 to 18 min and decreasing rates after 45 to 54 min. The GBCA was transported centrifugally and completely removed within 961-1086 min after administration., Conclusions: The exogenous GBCA leaked into the para-arterial glymphatics could be completely cleared around 961 to 1086 min after administration in a human model of BBB disruption. The tracer enhancement started variously in different intracranial regions but was eventually cleared centrifugally to brain convexity, probably towards glymphatic-meningeal lymphatics exits., Clinical Relevance Statement: Glymphatic clearance time intervals and the centrifugal directions assessed by a noninvasive approach may have implications for clinical glymphatic evaluation in the near future., Key Points: • This study aimed to investigate the human glymphatic dynamics in a noninvasive diseased model. • The intracranial MR-detectable gadolinium-based contrast agents were removed centrifugally within 961 to 1086 min. • The glymphatic dynamics was demonstrable by enhancing MRI in an in vivo diseased model noninvasively., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of Alzheimer's disease (AD), and decreased peripheral levels of this protein are associated with an increased risk of developing the disease. This study focuses on whether serum BDNF levels could be used as a predictor of AD progression., Methods: In this longitudinal observational study, we recruited cognition normal participants (N = 98) and AD (N = 442) from the Clinic at the Taipei Veterans General Hospital. We conducted a mini-mental status exam, a 12-item memory test, a categorical verbal fluency test, and a modified 15-item Boston naming test. A Serum BDNF level and apolipoprotein E ( APOE ) allele status were measured. The AD patients were followed prospectively. Based on the difference of MMSE scores, these patients were divided into fast decliners (decline ≥ 3/y) and slow decliners (MMSE decline < 3/y). Logistic regression was conducted to examine the impact of serum BDNF levels and other factor on the likelihood of AD patients being slow decliners. Pearson's correlation was used to estimate the relationship between serum BDNF levels and the score of neuropsychological tests., Results: In a logistic regression model containing serum BDNF levels, age, sex, APOE4 carrier status, education levels, and baseline MMSE score, higher serum BDNF levels were associated with a slower rate of cognitive decline in the AD group. Serum BDNF levels positively correlated with the results of multiple neuropsychological tests., Conclusion: BDNF is a protective factor against AD progression and likely plays a role in establishing a link between AD pathology and clinical manifestations., Competing Interests: Conflicts of interest: Dr. Jong-Ling Fuh, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Objectives: Clinical evidence has suggested that oral function is associated with cognitive, physical, and nutritional status of older people. A smaller volume of masseter, a crucial muscle for mastication, was associated with frailty. It has remained unknown if smaller masseter is associated with cognitive impairment. The current study investigated the association between masseter muscle volume, nutritional status, and cognitive status in older people., Materials and Methods: We recruited 19 patients with mild cognitive impairment (MCI), 15 patients with Alzheimer's disease (AD), and 28 sex and age-matched non-cognitive impairment (non-CI) older subjects. The number of missing teeth (NMT), masticatory performance (MP), maximal hand-grip force (MGF), and calf circumference (CC) were assessed. The masseter volume index (MVI) was calculated based on the masseter volume measured using magnetic resonance imaging., Results: The MVI was significantly lower in the AD group, compared to the MCI as well as the non-CI group. Multiple regression analyses revealed that the MVI was significantly associated with nutritional status (as indexed by CC) in the analysis of combination of NMT, MP, and the MVI. Moreover, the MVI was a significant predictor of CC only in patients with cognitive impairment (i.e., MCI+AD) but not in the non-CI group., Conclusions: Our findings suggested that in addition to the NMT and MP, masseter volume is a critical oral factor associated with cognitive impairment., Clinical Relevance: Reduction of MVI should be carefully monitored for patients with dementia and frailty, to whom a lower MVI may indicate worse nutrient intake., Competing Interests: Declaration of Conflicting Interest The authors report no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Mastication is associated with brain activation at the primary somatosensory cortex (S1) and the primary motor cortex (M1). Masticatory functions differ between patients with cognitive impairment (CI) and cognitively healthy older adults (non-CI). The association between cognitive health, brain network of functional connectivity, and mastication has remained unknown. The study investigated the association between masticatory performance (MP) and the topological feature of the functional network at the M1 and S1 in the CI and non-CI groups., Subjects and Methods: Forty-nine non-CI and 15 CI subjects received resting-state (rs) fMRI and assessment of MP. The topological feature of the M1 and S1 was quantified by eigenvector centrality (EC), an index that reflects a brain region as a functional "hub" of brain network., Results: In the non-CI group, MP was significantly correlated with EC of the left M1 and the right M1. The correlation was not statistically significant in the CI group. Cognitive status (CI or non-CI) and EC of the left M1 and the right M1, respectively, were statistically significant predictors to individual MP., Conclusion: Cognitive status and the topological feature of the M1 in the intrinsic functional network may contribute to the individual difference in masticatory function., (© 2022 Wiley Periodicals LLC.)

Objectives: The aim of this study was to investigate the functional networks in subjects with reversible cerebral vasoconstriction syndrome (RCVS) using resting-state functional magnetic resonance imaging (rs-fMRI)., Methods: We prospectively recruited patients with RCVS and healthy controls (HCs) between February 2017 and April 2021. The rs-fMRI data were analyzed using graph theory methods. We compared node-based global and regional topological metrics (Bundle 1) and network-based intranetwork and internetwork connectivity (Bundle 2) between RCVS patients and HCs. We also explored the associations of clinical and vascular (ie, the Lindegaard index, LI) parameters with significant rs-fMRI metrics., Results: A total of 104 RCVS patients and 93 HCs were included in the final analysis. We identified significantly decreased local efficiency of the left dorsal anterior insula (dAI; p = 0.0005) in RCVS patients within 30 days after disease onset as compared to HCs, which improved 1 month later. RCVS patients also had increased global efficiency (p = 0.009) and decreased average degree centrality (p = 0.045), clustering coefficient (p = 0.033), and assortativity values (p = 0.003) in node-based analysis. In addition, patients with RCVS had increased internetwork connectivity of the default mode network (DMN) with the salience (p = 0.027) and dorsal attention (p = 0.016) networks. Significant correlations between LI and regional local efficiency in left dAI (r s  = -0.418, p = 0.042) was demonstrated., Interpretation: The significantly lower local efficiency of the left dAI, suggestive of impaired central autonomic modulation, was negatively correlated with vasoconstriction severity, which is highly plausible for the pathogenesis of RCVS. ANN NEUROL 2023;94:772-784., (© 2023 American Neurological Association.)

Background: The Mild Behavioral Impairment Checklist (MBI-C) was developed to assess neuropsychiatric symptoms (NPS) and to identify mild behavioral impairment (MBI). This study validated the Taiwanese version of the MBI-C and examined its association of health-related quality of life (HR-QoL)., Methods: We recruited 242 older individuals without dementia (129 amnestic mild cognitive impairment, 113 cognitively normal). Their family completed the MBI-C, the Neuropsychiatric Inventory Questionnaire (NPI-Q), and instrumental activities of daily living scale. Participants completed the Geriatric Depression Scale (GDS-15), the Mini-Mental State Examination, the 12-item word recall test, the category verbal fluency test and the EuroQol 5 dimensions questionnaire (EQ-5D). Cronbach's α was used to evaluate the internal consistency of the MBI-C. Linear regression models were used to examined the association between MBI-C score and HR-QoL assessed using ED-5D., Results: The prevalence of MBI was 12% of all participants. Cronbach's α of the MBI-C was 0.893. The optimal cut-off point of MBI-C was 7.5 for identifying MBI, with a sensitivity of 100% and specificity of 85%. The MBI-C total score (β = -0.01, 95% confidence interval [CI] = -0.02 to -0.01, p < 0.001), MBI-C subdomain of decreased motivation (β = -0.04, 95% CI = -0.05 to -0.02, p < 0.001) and emotional dysregulation (β = -0.02, 95% CI = -0.04 to -0.004, p = 0.01) were factors related to EQ-5D index scores., Conclusion: Among older adults without dementia, the Taiwanese version of the MBI-C has good reliability and validity for detecting MBI. The total and subdomains of MBI-C were associated with decreased HR-QoL among individuals without dementia., (© 2023 John Wiley & Sons Ltd.)

Aims: Our aim was to differentiate patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from cognitively normal (CN) individuals and predict the progression from MCI to AD within a 3-year longitudinal follow-up. A newly developed Holo-Hilbert Spectral Analysis (HHSA) was applied to resting state EEG (rsEEG), and features were extracted and subjected to machine learning algorithms., Methods: A total of 205 participants were recruited from three hospitals, with CN ( n = 51, MMSE > 26), MCI ( n = 42, CDR = 0.5, MMSE ≥ 25), AD1 ( n = 61, CDR = 1, MMSE < 25), AD2 ( n = 35, CDR = 2, MMSE < 16), and AD3 ( n = 16, CDR = 3, MMSE < 16). rsEEG was also acquired from all subjects. Seventy-two MCI patients (CDR = 0.5) were longitudinally followed up with two rsEEG recordings within 3 years and further subdivided into an MCI-stable group (MCI-S, n = 36) and an MCI-converted group (MCI-C, n = 36). The HHSA was then applied to the rsEEG data, and features were extracted and subjected to machine-learning algorithms., Results: (a) At the group level analysis, the HHSA contrast of MCI and different stages of AD showed augmented amplitude modulation (AM) power of lower-frequency oscillations (LFO; delta and theta bands) with attenuated AM power of higher-frequency oscillations (HFO; beta and gamma bands) compared with cognitively normal elderly controls. The alpha frequency oscillation showed augmented AM power across MCI to AD1 with a reverse trend at AD2. (b) At the individual level of cross-sectional analysis, implementation of machine learning algorithms discriminated between groups with good sensitivity (Sen) and specificity (Spec) as follows: CN elderly vs. MCI: 0.82 (Sen)/0.80 (Spec), CN vs. AD1: 0.94 (Sen)/0.80 (Spec), CN vs. AD2: 0.93 (Sen)/0.90 (Spec), and CN vs. AD3: 0.75 (Sen)/1.00 (Spec). (c) In the longitudinal MCI follow-up, the initial contrasted HHSA between MCI-S and MCI-C groups showed significantly attenuated AM power of alpha and beta band oscillations. (d) At the individual level analysis of longitudinal MCI groups, deploying machine learning algorithms with the best seven features resulted in a sensitivity of 0.9 by the support vector machine (SVM) classifier, with a specificity of 0.8 yielded by the decision tree classifier., Conclusion: Integrating HHSA into EEG signals and machine learning algorithms can differentiate between CN and MCI as well as also predict AD progression at the MCI stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chu, Lei, Wu, Fuh, Wang, French, Chang, Chang, Huang, Liang and Juan.)