Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Background: and Purpose Syncope is characterized by the temporary loss of consciousness and is commonly associated with migraine. However, the genetic factors that contribute to this association are not well understood. This study investigated the specific genetic loci that make patients with migraine more susceptible to syncope as well as the genetic factors contributing to syncope and migraine comorbidity in a Han Chinese population in Taiwan. Methods: A genome-wide association study was applied to 1,724 patients with migraine who visited a tertiary hospital in Taiwan. The patients were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0 array and categorized into the following subgroups based on migraine type: episodic migraine, chronic migraine, migraine with aura, and migraine without aura. Multivariate regression analyses were used to assess the relationships between specific single-nucleotide polymorphisms (SNPs) and the clinical characteristics in patients with syncope and migraine comorbidity. Results: In patients with migraine, SNPs were observed to be associated with syncope. In particular, the rs797384 SNP located in the intron region of LOC102724945 was associated with syncope in all patients with migraine. Additionally, four SNPs associated with syncope susceptibility were detected in the nonmigraine control group, and these SNPs differed from those in the migraine group, suggesting distinct underlying mechanisms. Furthermore, the rs797384 variant in the intron region of LOC102724945 was associated with the score on the Beck Depression Inventory. Conclusions The novel genetic loci identified in this study will improve our understanding of the genetic basis of syncope and migraine comorbidity.

Background: and Purpose Syncope is characterized by the temporary loss of consciousness and is commonly associated with migraine. However, the genetic factors that contribute to this association are not well understood. This study investigated the specific genetic loci that make patients with migraine more susceptible to syncope as well as the genetic factors contributing to syncope and migraine comorbidity in a Han Chinese population in Taiwan. Methods: A genome-wide association study was applied to 1,724 patients with migraine who visited a tertiary hospital in Taiwan. The patients were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0 array and categorized into the following subgroups based on migraine type: episodic migraine, chronic migraine, migraine with aura, and migraine without aura. Multivariate regression analyses were used to assess the relationships between specific single-nucleotide polymorphisms (SNPs) and the clinical characteristics in patients with syncope and migraine comorbidity. Results: In patients with migraine, SNPs were observed to be associated with syncope. In particular, the rs797384 SNP located in the intron region of LOC102724945 was associated with syncope in all patients with migraine. Additionally, four SNPs associated with syncope susceptibility were detected in the nonmigraine control group, and these SNPs differed from those in the migraine group, suggesting distinct underlying mechanisms. Furthermore, the rs797384 variant in the intron region of LOC102724945 was associated with the score on the Beck Depression Inventory. Conclusions The novel genetic loci identified in this study will improve our understanding of the genetic basis of syncope and migraine comorbidity.

Background: and Purpose Syncope is characterized by the temporary loss of consciousness and is commonly associated with migraine. However, the genetic factors that contribute to this association are not well understood. This study investigated the specific genetic loci that make patients with migraine more susceptible to syncope as well as the genetic factors contributing to syncope and migraine comorbidity in a Han Chinese population in Taiwan. Methods: A genome-wide association study was applied to 1,724 patients with migraine who visited a tertiary hospital in Taiwan. The patients were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0 array and categorized into the following subgroups based on migraine type: episodic migraine, chronic migraine, migraine with aura, and migraine without aura. Multivariate regression analyses were used to assess the relationships between specific single-nucleotide polymorphisms (SNPs) and the clinical characteristics in patients with syncope and migraine comorbidity. Results: In patients with migraine, SNPs were observed to be associated with syncope. In particular, the rs797384 SNP located in the intron region of LOC102724945 was associated with syncope in all patients with migraine. Additionally, four SNPs associated with syncope susceptibility were detected in the nonmigraine control group, and these SNPs differed from those in the migraine group, suggesting distinct underlying mechanisms. Furthermore, the rs797384 variant in the intron region of LOC102724945 was associated with the score on the Beck Depression Inventory. Conclusions The novel genetic loci identified in this study will improve our understanding of the genetic basis of syncope and migraine comorbidity.

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g -1 •hour -1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2 + -Beclin 1 + and SOX2 + -S100β + cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

Objective: Schizophrenia has been associated with dysfunction of the hypothalamic-pituitary-adrenal axis. Furthermore, alterations in neurotrophic factors might contribute to the pathogenesis of schizophrenia. We aimed to evaluate the effects of a simulated laughter intervention on the levels of cortisol and BDNF and to determine whether the effects associated with simulated laughter could be sustained after discontinuation of the intervention. Methods: In this randomized controlled study, patients with schizophrenia according to DSM-IV clinical criteria were randomly assigned to receive either 8-week-long simulated laughter intervention (n=32) or treatment-as-usual group (control group, n=27). The serum levels of BDNF and cortisol were measured at baseline, week 8, and four weeks after discontinuation (week 12) of the intervention program. Results: After an 8-week simulated laughter intervention, the laughter group had significantly higher levels of BDNF; however, four weeks after discontinuation of the intervention, the levels of BDNF significantly dropped. Interestingly, the levels of cortisol did not change significantly at week 8, but they were significantly elevated at week 12. The levels of BDNF and cortisol in the control group did not change significantly between week 0 and week 8. Conclusion These findings suggest that the simulated laughter intervention has an early effect on neurogenesis with a significant delayed effect on stress regulation in subjects with schizophrenia.