Implications of helplessness in depression: diagnosing mild cognitive impairment and analyzing its effects on cognitive decline in older adults.

Background: This study focuses on how elements of depression correlate with mild cognitive impairment (MCI) in older adults and the diagnostic efficacy of combining these components with the Mini-Mental State Examination (MMSE). The study also investigated the connection between individual depression components and overall cognitive function, as measured by the total score (TS) of the consortium to establish a registry for Alzheimer's disease (AD) assessment battery. Methods: The study included 196 nondemented adults aged 65 to 90 years at a university hospital and community. Comprehensive clinical assessments including the 30-item Geriatric Depression Scale (GDS) to measure components of depressive symptoms, TS, and blood nutritional biomarkers. Results: Our stepwise logistic regression analysis highlighted the 'helplessness item' (odds ratio = 4.531, 95% CI = 2.218 to 9.258, p < 0.001) as a significant predictor for MCI diagnosis. Further, models incorporating 'helplessness item + MMSE' demonstrated markedly enhanced accuracy in diagnosing MCI, surpassing the performance of the MMSE used independently. Notably, the group characterized by helplessness showed a significant reduction in TS (B = -5.300, SE = 1.899, ß = -0.162, p = 0.006), with this trend being particularly pronounced in individuals exhibiting lower levels of physical activity. Interestingly, this correlation did not manifest in participants with higher physical activity levels. Conclusion: Our findings suggest that helplessness is highly effective in diagnosing MCI and is linked to a decrease in cognitive function. Therefore, when addressing MCI and AD-related cognitive decline, clinicians should consider helplessness.

High-intensity walking in midlife is associated with improved memory in physically capable older adults.

BACKGROUND: Little is known about the associations of midlife- and late life-initiated walking with Alzheimer's disease (AD)-related cognitive decline in humans. We aimed to investigate whether high-intensity, prolonged, midlife-initiated walking is associated with changes in AD-related cognitive decline in physically capable older adults. METHODS: We studied 188 physically capable participants aged 65-90 years without dementia who underwent comprehensive clinical assessment, including of their walking modality (i.e., intensity, duration, midlife- or late life-onset), memory- or non-memory and total cognitive performance, and blood or nutritional biomarkers. RESULTS: The walking group showed better episodic memory (B = 2.852, SE = 1.214, ß = 0.144, p = 0.020), but not non-memory cognition, than the non-walking group. High-intensity walking starting in midlife was significantly associated with better episodic memory (B = 9.360, SE = 3.314, ß = 0.446, p = 0.005) compared to the non-walking group. In contrast, there were no differences in cognition according to walking duration, regardless of the onset time. The walking group also showed a similar association with overall cognition. CONCLUSIONS: Among physically capable older adults without dementia, walking, particularly at high intensity and starting in midlife, is associated with improved episodic memory, an AD-related cognitive domain. Further attention should be paid to the role of walking in terms of AD prevention.

Manganese level and cognitive decline in older adults with the APOE e4 allele: a preliminary study.

This study examined the relationship between serum manganese level and cognition, and the moderating effect of apolipoprotein E ε4 (APOE4) on this relationship. A total of 164 non-demented participants underwent clinical assessments including serum manganese level and cognition [episodic memory score (EMS), non-memory score (NMS) for executive function/attention/language/ visuospatial skill, and total score (TS)]. Serum manganese × APOE4 interaction had a significant effect on EMS and TS. Serum manganese level was inversely associated with EMS and TS in APOE4-positive but not APOE4-negative participants. APOE4 should be considered a key component in Alzheimer's disease studies that included manganese imbalance as a risk factor.

Association between physical activity and episodic memory and the moderating effects of the apolipoprotein E ε4 allele and age.

Background: An abundance of evidence indicates that physical activity may protect against Alzheimer's disease (AD) and related cognitive decline. However, little is known about the association between physical activity and AD-related cognitive decline according to age and the apolipoprotein E (APOE) ε4 allele (APOE4) as major risk factors. Therefore, we examined whether age and APOE4 status modulate the effects of physical activity on episodic memory as AD-related cognition in non-demented older adults. Methods: We enrolled 196 adults aged between 65 and 90 years, with no dementia. All participants underwent comprehensive clinical assessments including physical activity evaluation and APOE genotyping. The AD-related cognitive domain was assessed by the episodic memory, as the earliest cognitive change in AD, and non-memory cognition for comparative purposes. Overall cognition was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. Results: We found significant physical activity × age and physical activity × APOE4 interaction effects on episodic memory. Subgroup analyses indicated that an association between physical activity and increased episodic memory was apparent only in subjects aged > 70 years, and in APOE4-positive subjects. Conclusion: Our findings suggest that physical activity has beneficial effects on episodic memory, as an AD-related cognitive domain, in individuals aged > 70 years and in APOE4-positive individuals. Physicians should take age and APOE4 status account into when recommending physical activity to prevent AD-related cognitive decline.

Influence of Sensory Impairments on Incidence of Dementia in the Korean Population.

OBJECTIVE: Previous studies have shown the influence of visual and auditory sensory impairment on dementia incidence. In this study, we tested the hypothesis that the incidence of dementia will increase with visual and auditory impairments than with visual or auditory impairment. METHODS: Data from the Korea National Health Insurance Service database were used, including disease and medication codes from 2009 to 2018, and the 2011 national health check-up results. Participants were grouped based on their sensory abilities: normal, visual impairment, auditory impairment, and both visual and auditory impairments (dual sensory impairment). To compare the incidence of dementia, hazard ratios were calculated for each group, with reference to the normal sensory (NS) group. Sensitivity analyses were performed comparing dementia incidence from 2014 to 2018, excluding the onset of the disease in 2012 and 2013. RESULTS: We identified 8,289 cases of dementia during the seven-year follow-up. In the multiple Cox regression analysis, adjusted for sex, social economic status, age, comorbidities, smoking, alcohol consumption, and activity level, the auditory impairment (hazard ratio= 1.1908) and visual impairment (hazard ratio=1.3553) groups showed a significantly higher dementia incidence than the NS group. Dual sensory impairment (hazard ratio=1.5267) showed the highest incidence. The sensitivity analysis yielded similar results. CONCLUSION: Visual and auditory impairments are associated with an increased risk of dementia, particularly in individuals with dual sensory impairment. Hence, visual and auditory impairments might have increased the risk of dementia through independent pathological processes. Therefore, preventing and correcting sensory impairment is necessary to reduce the risk of dementia.

Ginseng intake and Alzheimer disease-specific cognition in older adults according to apolipoprotein ε4 allele status.

Background: The probable association among ginseng intake, Alzheimer's disease (AD)-specific cognition, and apolipoprotein ε4 (APOE4) remains poorly investigated. Hence, we examined the association between ginseng intake and AD-specific cognition in older adults under the moderating effect of APOE4 status. Methods: This study enrolled 160 adults aged 65-90 years without dementia. All participants underwent comprehensive dietary and clinical assessments including ginseng intake, AD-related cognition (i.e., delayed episodic memory, as the earliest cognitive change in AD), and non-memory cognition for comparative purposes. Results: Ginseng intake was associated with higher delayed episodic memory, but not non-memory cognition, compared to no ginseng intake. The interaction between ginseng intake and APOE4 status had a significant effect on delayed episodic memory. Subgroup analyses showed that ginseng intake was associated with higher delayed episodic memory in the APOE4-negative but not the APOE4-positive subgroup. The benefits of ginseng intake on delayed episodic memory were prominent in the high duration (≥5 years) and midlife onset (<65 years) groups. Conclusion: Our study of older adults with no dementia suggests that ginseng intake (with high duration and midlife onset) had a beneficial effect on AD-specific cognitive decline, i.e., the delayed episodic memory. In addition, APOE4 status moderates the association between ginseng intake status and AD-specific cognitive decline.

Spicy food intake predicts Alzheimer-related cognitive decline in older adults with low physical activity.

A plausible association exists among spicy food consumption, physical activity, and Alzheimer's disease (AD) or cognitive decline, but it remains poorly investigated. We aimed to examined the association between spicy food and AD-related memory decline or global cognitive decline in older adults under the moderating effect of physical activity. Total 196 non-demented older adults were included. Participants underwent comprehensive dietary and clinical assessments including spicy food intake, AD-related memory, global cognition, and physical activity. The strength of spicy food was stratified into three categories: 'not spicy' (reference), 'low spiciness', and 'high spiciness'. Multiple linear regression analyses were performed to examine the relationships between spicy level and cognition. The spicy level was the independent variable in each analysis; it was entered as a stratified categorical variable using the three categories. We found a significant association between a high level of spiciness in food and decreased memory ([Formula: see text] - 0.167, p < 0.001) or global cognition ([Formula: see text] - 0.122, p = 0.027), but not non-memory cognition. To explore the moderating effects of age, sex, apolipoprotein E ε4 allele-positivity, vascular risk score, body mass index, and physical activity on the associations between spicy level and memory or global cognition, the same regression analyses were repeated including two-way interaction terms between the spicy level and each of the six variables as an additional independent variable. An interactive effect was detected between a high level of spiciness in food and physical activity on the memory ([Formula: see text] 0.209, p = 0.029) or global cognition ([Formula: see text] 0.336, p = 0.001). Subgroup analyses showed that the association between a high level of spiciness in food and a lower memory ([Formula: see text] - 0.254, p < 0.001) and global score ([Formula: see text] - 0.222, p = 0.002) was present only in older adults with low physical activity, but not in older adults with high physical activity. Our findings suggest that spicy food intake is predictive of AD-related cognitive decline, i.e., episodic memory; this relationship is worsened by physically inactive lifestyle.

A combination of midlife diabetes mellitus and the apolipoprotein E ε4 allele increase risk for cognitive decline.

Background: It has been suggested that diabetes mellitus (DM) and the apolipoprotein E (APOE) ε4 allele (APOE4) increase the risk for Alzheimer's disease (AD) and cognitive decline. However, the evidence is sparse. We explored whether APOE4 status modulated the effects of midlife and late-life DM on global cognition of non-demented older adults. Methods: In all, 176 non-demented adults (age 65-90 years) were enrolled. All the participants underwent comprehensive clinical assessments including midlife and late-life DM evaluation and APOE genotyping. The global cognitive performance index was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. Results: We found a significant midlife DM × APOE4 interaction effect on the global cognitive performance. Subgroup analyses indicated that an association between midlife DM and decreased global cognitive performance was apparent only in older adults who were APOE4-positive, and not in those with APOE4-negative. Conclusion: Our findings from non-demented older adults suggest that midlife DM increases the risk for AD and cognitive decline, and this risk is modulated by APOE4 status. To prevent AD and cognitive decline, physicians should check for the possible coexistence of midlife DM and APOE4-positive status.

Association of a History of Sleep Disorder With Risk of Mild Cognitive Impairment and Alzheimer's Disease Dementia.

OBJECTIVE: We explored whether a history of sleep disorder affected a current diagnosis of cognitive impairment and clinical conversion in a non-demented elderly population. METHODS: Comprehensive clinical data collected as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI) was analyzed. A history of sleep disorder was recorded in the recent ADNI medical database. Standard clinical and neuropsychological tests were performed both at baseline and follow-up visit. Multiple logistic regression analysis was performed after adjusting for age, sex, education, apolipoprotein E ε4 status, vascular risk score, body mass index, Geriatric Depression Scale score, and use of sleeping pills. RESULTS: A total of 391 cognitively normal individuals, 303 with early mild cognitive impairment (MCI) and 364 with late MCI were included. Sleep disorder history was significantly associated with an increased risk of MCI but not with clinical conversion. A history of insomnia or obstructive sleep apnea (OSA) significantly increased the risk of MCI, but only an OSA history predicted progression to Alzheimer's disease (AD) dementia. CONCLUSION: Our findings suggest that a sleep disorder history usefully aids early detection of cognitive impairment and emphasize that such sleep disorder, particularly OSA, is important as potential target for AD prevention.

Brain Amyloid Index as a Probable Marker Bridging Between Subjective Memory Complaint and Objective Cognitive Performance.

Background: The association between types of subjective memory complaint (SMC), poor objective cognitive performance, and brain Aß deposition have been poorly understood. We investigated the association between types of SMC and objective global cognitive performance, then assessed whether this association is mediated by the brain amyloid prediction index (API). Methods: In total, 173 non-demented older adults [63 cognitively normal (CN) and 110 mild cognitive impairment (MCI)] underwent comprehensive clinical assessments. Objective global cognitive performance and brain amyloid index were measured using the total score (TS) of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery and API, respectively. In total, four items of SMC from the subjective memory complaints questionnaire (SMCQ) (SMCQ1: a feeling of memory problem; SMCQ2: the feeling of worse memory than 10 years ago; SMCQ3: the feeling of worse memory than others of similar age; or SMCQ4: the feeling of difficulty in everyday life) in global memory function were assessed. Results: In non-demented and participants with MCI, SMCQ3-positive and SMCQ4-positive groups were associated with decreased TS. In participants with MCI, the SMCQ3-positive group was associated with increased API, and API was associated with decreased TS, but the SMCQ4-positive group did not. In addition, the association between the SMCQ3-positive group and poor TS disappeared when API was controlled as a covariate, indicating that API has a mediation effect. Conclusion: The present findings suggest that SMC, a feeling of worse memory performance than others in a similar age group, in the older adults without dementia is associated with poor objective cognitive performance via increased brain amyloid index.

Association Between Enlarged Perivascular Spaces and Cognition in a Memory Clinic Population.

BACKGROUND AND OBJECTIVES: Although enlarged perivascular spaces (EPVS) have been suggested as an emerging measure of small vessel disease (SVD) in the brain, their association with cognitive impairment is not yet clearly understood. We aimed to examine the relationship between each EPVS in the basal ganglia (BG-EPVS) and centrum semiovale (CSO-EPVS) with cognition in a memory clinic population. METHODS: Participants with a diverse cognitive spectrum were recruited from a university hospital memory clinic. They underwent comprehensive clinical and neuropsychological assessments and brain MRI. BG-EPVS and CSO-EPVS were measured on T2-weighted MRI and then dichotomized into low and high degrees for further analyses. Other SVD markers were assessed using validated rating scales. RESULTS: A total of 910 participants were included in this study. A high degree of BG-EPVS was significantly associated with poorer scores on the executive function domain, but not with other cognitive domains, when age, sex, education, MRI scanner type, and cognitive diagnosis were controlled as covariates. However, the association between BG-EPVS and executive function was no longer significant after controlling for other markers of SVD, such as lacunar infarcts and periventricular white matter hyperintensities, as additional covariates. CSO-EPVS did not have a significant relationship with any cognitive scores, regardless of the covariates. DISCUSSION: Our findings from a large memory clinic population suggest that EPVS, regardless of the topographical location, may not be used as a specific SVD marker for cognitive impairment, although an apparent association was observed between a high degree of BG-EPVS and executive dysfunction before controlling other SVD markers that share a common pathophysiologic process with BG-EPVS.

Association Between Copper and Global Cognition and the Moderating Effect of Iron.

Background: Despite the known association between abnormal serum copper levels and Alzheimer's disease (AD) or cognitive decline, the association between copper, iron, and cognition remains poorly investigated. We examined the association between serum copper levels and global cognition measured using the Mini-Mental State Examination (MMSE) in older adults with normal copper levels. We also explored the moderating effect of iron on this association. Methods: The study enrolled 99 non-demented adults between 65 and 90 years of age. All the participants underwent comprehensive clinical assessments and serum copper measurements. Global cognitive performance was measured by the MMSE. All copper levels were within the normal range and were stratified into three categories: < 87 (low), 87-98 (medium), and > 98 (high: used as a reference category) µg/dL. Results: Serum copper level (as a continuous variable) was significantly associated with MMSE score (B = 0.065, 95% confidence interval = 0.023-0.108, p = 0.003). Low serum copper group showed significantly decreased MMSE score compared to high copper one (B = -2.643, 95% confidence interval = -4.169 to -1.117, p < 0.001), while middle copper category had no difference (B = -1.211, 95% confidence interval = -2.689 to 0.268, p = 0.107). There was a significant low serum copper ×iron interaction effect on the MMSE score (B = 0.065, 95% confidence interval = 0.016-0.114, p = 0.010). Subgroup analyses showed that low serum copper was significantly associated with a low MMSE score in the low-iron (B = -4.174, 95% confidence interval = -6.607 to -1.741, p = 0.001) but not high-iron subgroup (B = -0.721, 95% confidence interval = -2.852 to 1.409, p = 0.495). Conclusion: Our findings from non-demented older adults suggest that a low serum copper level within the normal range was associated with AD or cognitive decline and this is moderated by iron. To prevent AD or cognitive decline, clinicians need to pay attention to avoiding low serum copper and iron levels, even within the clinical normal range.

Late-Life Physical Activities Moderate the Relationship of Amyloid-ß Pathology with Neurodegeneration in Individuals Without Dementia.

BACKGROUND: Physical activities (PA) have been suggested to reduce the risk of Alzheimer's disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited. OBJECTIVE: We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia. METHODS: This study included participants from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging. Using the multi-modal brain imaging data, in vivo AD pathologies including global amyloid deposition, AD-signature region cerebral glucose metabolism (AD-CM), and AD-signature region cortical thickness (AD-CT) were quantified. Both midlife and late-life PA of participants were measured using the Lifetime Total Physical Activity Questionnaire. RESULTS: This study was performed on 260 participants without dementia (195 with normal cognitive function and 65 with mild cognitive impairment). PA of neither midlife nor late-life showed direct correspondence with any neuroimaging biomarker. However, late-life PA moderated the relationship of brain amyloid-ß (Aß) deposition with AD-CM and AD-CT. Aß positivity had a significant negative effect on both AD-CM and AD-CT in individuals with lower late-life PA, but those with higher late-life PA did not show such results. Midlife PA did not have such a moderation effect. CONCLUSION: The findings suggest that physically active lifestyle in late-life, rather than that in midlife, may delay AD-associated cognitive decline by decreasing Aß-induced neurodegenerative changes in old adults.

A 9-Year Comparison of Dementia Prevalence in Korea: Results of NaSDEK 2008 and 2017.

BACKGROUND: In many high-income Western countries, the prevalence of dementia had been reduced over the past decades. OBJECTIVE: We investigated whether the prevalence of all-cause dementia, Alzheimer's disease, vascular dementia, and mild cognitive impairment (MCI) had changed in Korea from 2008 to 2017. METHODS: Nationwide Survey on Dementia Epidemiology of Korea (NaSDEK) in 2008 and 2017 was conducted on representative elderly populations that were randomly sampled across South Korea. Both surveys employed a two-stage design (screening and diagnostic phases) and diagnosed dementia and MCI according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the consensus criteria from the International Working Group, respectively. The numbers of participants aged 65 years or older in the screening and diagnostic phases were 6,141 and 1,673 in the NaSDEK 2008 and 2,972 and 474 in the NaSDEK 2017, respectively. RESULTS: The age- and sex-standardized prevalence of all-cause dementia and Alzheimer's disease showed nonsignificant decrease (12.3% to 9.8%, odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.54-1.48 for all-cause dementia; 7.6% to 6.8%, OR [95% CI] = 0.91 [0.58-1.42] for Alzheimer's disease). Vascular dementia decreased in the young-old population aged less than 75 years (2.7% to 0.001%, OR [95% CI] = 0.04 [0.01-0.15]) and in women (1.9% to 0.5%, OR [95% CI] = 0.27 [0.10-0.72]) while MCI remained stable (25.3% to 26.2%, OR [95% CI] = 1.08 [0.67-1.73]). CONCLUSION: We found that the prevalence of dementia in Korea showed a nonsignificant decrease between 2008 and 2017.

Differential associations of age and Alzheimer's disease with sleep and rest-activity rhythms across the adult lifespan.

This study aimed to identify differences between physiological age-related and Alzheimer's disease (AD)-related alterations in sleep and rest-activity rhythm. All participants (n = 280; 20-90 years) underwent clinical assessments, [11C] Pittsburgh compound B-positron emission tomography, and actigraphic monitoring. In cognitively normal adults without cerebral amyloid-ß, older age was associated with earlier timing of circadian phase and robust rest-activity rhythm, but sleep quantity and quality were mostly unaffected by age. While preclinical AD was associated with earlier circadian timing, clinical AD exhibited later timing of daily rhythm and increased sleep duration. In conclusion, our findings suggest that older age itself leads to a more regular daily activity rhythm, but does not affect sleep duration. While preclinical AD made the effects of age-related phase advance more prominent, clinical AD was related to later circadian timing and increased sleep duration.

Olanzapine-induced Concurrent Tardive Dystonia and Tardive Dyskinesia in Schizophrenia with Intellectual Disability: A Case Report.

Tardive dystonia and tardive dyskinesia (TDs) are rare extrapyramidal side effects that develop after long-term use of antipsychotics, but they are different syndromes and rarely occur at the same time. Olanzapine is an atypical antipsychotic drug associated with a low risk of extrapyramidal side effects in schizophrenia, but its associations with tardive movements are not clear. We present a case of a 19-year-old Asian female patient with schizophrenia and intellectual disabilities who developed concurrent TDs after long-term use of olanzapine. At her 10-month follow-up examination, her concurrent TDs had been treated successfully with clozapine. This case demonstrates that although the use of olanzapine to treat psychosis and behavioral disturbances is increasing due to its high efficacy and low rate of extrapyramidal side effects, concurrent TDs should be carefully assessed after long-term use of this antipsychotic, especially in patients with schizophrenia and intellectual disabilities. Clozapine, by preventing or reversing the debilitating consequences of concurrent TDs, may be an effective treatment for these patients.

MMSE Subscale Scores as Useful Predictors of AD Conversion in Mild Cognitive Impairment.

PURPOSE: This study was performed to examine the usefulness of subscores on the Mini-Mental State Examination (MMSE) for predicting the progression of Alzheimer's disease (AD) dementia in individuals with mild cognitive impairment (MCI). PATIENTS AND METHODS: A total of 306 MCI individuals in the Alzheimer's Disease Neuroimaging Initiative database were included in the study. Standardized clinical and neuropsychological tests were performed at baseline and at 2-year follow-up. Logistic regression analysis was conducted to examine the MMSE total and subscale scores to predict progression to AD dementia in MCI individuals. RESULTS: The MMSE total score and the MMSE memory, orientation, and construction subscores were inversely associated with AD progression after controlling for all potential confounders; MMSE attention and language subscores were not correlated with AD progression. The MMSE delayed recall score among the MMSE memory subscores and the MMSE time score among the orientation subscores, especially week and day, were inversely associated with AD progression; the MMSE immediate recall and place scores were not correlated with progression. CONCLUSION: Our findings suggest that the MMSE memory, orientation, and construction subscores, which are simple and readily available clinical measures, could provide useful information to predict AD dementia progression in MCI individuals in practical clinical settings.

Sleep experiences during different lifetime periods and in vivo Alzheimer pathologies.

BACKGROUND: Very little is known for the direction or causality of the relationship between lifetime sleep experiences and in vivo Alzheimer's disease (AD) pathologies. This study aimed to examine the relationship between sleep experiences during the young adulthood, midlife, and late-life periods and in vivo cerebral beta-amyloid (Aß) deposition and AD signature regional neurodegeneration in cognitively normal (CN) old adults. METHODS: This study included 202 CN old adults who participated in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) study. All participants underwent a comprehensive clinical assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] Fluorodeoxyglucose-PET, and magnetic resonance imaging. The quality and duration of sleep were assessed for the following age periods: 20-30s, 40-50s, and the most recent month. All analyses were adjusted for age, gender, education, apolipoprotein E ε4 status, vascular risk score, Hamilton Depression Rating Scale score, and use of sleep medication. RESULTS: Bad sleep quality and short sleep duration during midlife were significantly associated with increased Aß deposition and AD signature regional hypometabolism, respectively. Although current bad sleep quality appeared to be associated with increased Aß accumulation, this association disappeared after controlling for the effects of midlife sleep quality. Neither the quality nor duration of sleep during young adulthood was related to Aß burden or neurodegeneration. CONCLUSIONS: Bad sleep quality during midlife increases pathological Aß deposition in the brain, while short sleep duration during the same period accelerates regional hypometabolism.

Combination of the CAGE and serum gamma-glutamyl transferase: an effective screening tool for alcohol use disorder and alcohol dependence.

Purpose: The CAGE is a convenient test for alcohol-related disorder due to its brevity, but it is not as effective as the alcohol use disorders identification test (AUDIT). Gamma-glutamyl transferase (GGT) is an objective blood biochemical marker of excessive alcohol intake; however, it has low sensitivity. This study tested the performance of the combined use of CAGE and GGT to screen problem drinking (PD), alcohol use disorder (AUD), and alcohol dependence (AD). Methods: A total of 394 subjects composed of 91 normal controls and 303 subjects with PD were enrolled in this study. Of the PD subjects, 147 were diagnosed with AUD (77 alcohol abuse and 70 AD). A series of multiple logistic regression models for PD, AUD, and AD discrimination were used to obtain new combined CAGE and GGT scores after adjusting for age and gender (CAGE+GGT). A receiver operating characteristic curve analysis was conducted to determine how well the CAGE+GGT score discriminated between individuals with PD, AUD, and AD. Results: The discrimination accuracy of the AUDIT for PD was significantly better than that of the CAGE or the CAGE+GGT (z=6.927, p<0.0001; z=5.301, p<0.0001, respectively). The CAGE and the CAGE+GGT were better than the AUDIT at discriminating AUD (z=2.535, p=0.0112; z=2.894, p=0.0038, respectively). The discrimination accuracy of the AUDIT for AD was significantly better than that of the CAGE and GGT (z=3.233, p=0.0012; z=6.529, p<0.0001, respectively), but the CAGE+GGT was comparable with the AUDIT (z=1.652, p=0.0985). Conclusion: Our findings support the combined use of the CAGE questionnaire and serum GGT level as a sensitive and useful tool for AD screening.

Region-specific association between basal blood insulin and cerebral glucose metabolism in older adults.

BACKGROUND: Although previous studies have suggested that insulin plays a role in brain function, it still remains unclear whether or not insulin has a region-specific association with neuronal and synaptic activity in the living human brain. We investigated the regional pattern of association between basal blood insulin and resting-state cerebral glucose metabolism (CMglu), a proxy for neuronal and synaptic activity, in older adults. METHOD: A total of 234 nondiabetic, cognitively normal (CN) older adults underwent comprehensive clinical assessment, resting-state 18F-fluodeoxyglucose (FDG)-positron emission tomography (PET) and blood sampling to determine overnight fasting blood insulin and glucose levels, as well as apolipoprotein E (APOE) genotyping. RESULTS: An exploratory voxel-wise analysis of FDG-PET without a priori hypothesis demonstrated a positive association between basal blood insulin levels and resting-state CMglu in specific cerebral cortices and hippocampus, rather than in non-specific overall cerebral regions, even after controlling for the effects of APOE e4 carrier status, vascular risk factor score, body mass index, fasting blood glucose, and demographic variables. Particularly, a positive association of basal blood insulin with CMglu in the right posterior hippocampus and adjacent parahippocampal region as well as in the right inferior parietal region remained significant after multiple comparison correction. Conversely, no region showed negative association between basal blood insulin and CMglu. CONCLUSIONS: Our finding suggests that basal fasting blood insulin may have association with neuronal and synaptic activity in specific cerebral regions, particularly in the hippocampal/parahippocampal and inferior parietal regions.