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.

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.

Brain Structural Alterations, Diabetes Biomarkers, and Cognitive Performance in Older Adults With Dysglycemia.

Despite the high risk of dementia in older adults with type 2 diabetes, the neuroanatomical correlates of cognitive dysfunction that are particularly affected by diabetes are not well characterized. This study is aimed to examine the structural brain alterations in dysglycemic older adults. Using voxel-based morphometric and tract-based spatial statistics, we examined changes in gray matter volume, white matter volume, and microstructural integrity in older adults with prediabetes and diabetes. We also assessed the correlation of these structural changes with diabetes biomarkers and cognitive performance. A total of 74 non-demented older adults (normal, n = 14; prediabetes, n = 37; and diabetes, n = 23) participated in this study and underwent structural and diffusion magnetic resonance imaging (MRI) scans and neuropsychological tests. Subjects with diabetes showed reduced volume of cerebellar gray matter and frontal white matter and diffuse white matter dysintegrity, while those with prediabetes only showed reduced volume of insular gray matter. Atrophic changes in the cerebellum and frontal lobe and frontal white matter dysintegrity were correlated with chronic hyperglycemia and insulin resistance and worse performance in verbal memory recognition and executive function tests. Our findings suggest that chronic hyperglycemia and insulin resistance may alter brain structures forming the fronto-cerebellar network, which may cause cognitive dysfunction in older adults.

Long-Term Exposure to PM10 and in vivo Alzheimer's Disease Pathologies.

BACKGROUND: Previous studies indicated an association between Alzheimer's disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10µm (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association. OBJECTIVE: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging. METHODS: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11C-Pittsburg compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging scans. A subset of 78 participants also underwent 18F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10µm over the past 5 years (PM10mean) collected from air pollution surveillance stations were matched to each participant's residence. RESULTS: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-ß (Aß) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure. CONCLUSION: The findings suggest that long-term exposure to PM10 may contribute to pathological Aß deposition.

Association of carotid and intracranial stenosis with Alzheimer's disease biomarkers.

BACKGROUND: To clarify whether atherosclerosis of the carotid and intracranial arteries is related to Alzheimer's disease (AD) pathology in vivo, we investigated the associations of carotid and intracranial artery stenosis with cerebral beta-amyloid (Aß) deposition and neurodegeneration in middle- and old-aged individuals. Given different variations of the pathologies between cognitive groups, we focused separately on cognitively normal (CN) and cognitively impaired (CI) groups. METHODS: A total of 281 CN and 199 CI (mild cognitive impairment and AD dementia) subjects underwent comprehensive clinical assessment, [11C] Pittsburgh compound B-positron emission tomography, and magnetic resonance (MR) imaging including MR angiography. We evaluated extracranial carotid and intracranial arteries for the overall presence, severity (i.e., number and degree of narrowing), and location of stenosis. RESULTS: We found no associations between carotid and intracranial artery stenosis and cerebral Aß burden in either the CN or the CI group. In terms of neurodegeneration, exploratory univariable analyses showed associations between the presence and severity of stenosis and regional neurodegeneration biomarkers (i.e., reduced hippocampal volume [HV] and cortical thickness in the AD-signature regions) in both the CN and CI groups. In confirmatory multivariable analyses controlling for demographic covariates and diagnosis, the association between number of stenotic intracranial arteries ≥ 2 and reduced HV in the CI group remained significant. CONCLUSIONS: Neither carotid nor intracranial artery stenosis appears to be associated with brain Aß burden, while intracranial artery stenosis is related to amyloid-independent neurodegeneration, particularly hippocampal atrophy.

Prediction of Amyloid Positivity in Mild Cognitive Impairment Using Fully Automated Brain Segmentation Software.

OBJECTIVE: To assess the predictive ability of regional volume information provided by fully automated brain segmentation software for cerebral amyloid positivity in mild cognitive impairment (MCI). METHODS: This study included 130 subjects with amnestic MCI who participated in the Korean brain aging study of early diagnosis and prediction of Alzheimer's disease, an ongoing prospective cohort. All participants underwent comprehensive clinical assessment as well as 11C-labeled Pittsburgh compound PET/MRI scans. The predictive ability of volumetric results provided by automated brain segmentation software was evaluated using binary logistic regression and receiver operating characteristic curve analysis. RESULTS: Subjects were divided into two groups: one with Aß deposition (58 subjects) and one without Aß deposition (72 subjects). Among the varied volumetric information provided, the hippocampal volume percentage of intracranial volume (%HC/ICV), normative percentiles of hippocampal volume (HCnorm), and gray matter volume were associated with amyloid-ß (Aß) positivity (all P < 0.01). Multivariate analyses revealed that both %HC/ICV and HCnorm were independent significant predictors of Aß positivity (all P < 0.001). In addition, prediction scores derived from %HC/ICV with age and HCnorm showed moderate accuracy in predicting Aß positivity in MCI subjects (the areas under the curve: 0.739 and 0.723, respectively). CONCLUSION: Relative hippocampal volume measures provided by automated brain segmentation software can be useful for screening cerebral Aß positivity in clinical practice for patients with amnestic MCI. The information may also help clinicians interpret structural MRI to predict outcomes and determine early intervention for delaying the progression to Alzheimer's disease dementia.

Serum albumin and beta-amyloid deposition in the human brain.

OBJECTIVES: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral ß-amyloid (Aß) protein deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH), in the human brain. METHODS: A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [11C] Pittsburgh compound B-PET, 18F-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.4 g/dL (low albumin), 4.4 to 4.5 g/dL (middle albumin), and >4.5 g/dL (high albumin; used as a reference category). Aß positivity, AD-signature region cerebral glucose metabolism (AD-CM), AD-signature region cortical thickness (AD-CT), and WMH volume were used as outcome measures. RESULTS: Serum albumin level (as a continuous variable) was inversely associated with Aß deposition and Aß positivity. The low albumin group showed a significantly higher Aß positivity rate compared to the high albumin group (odds ratio 3.40, 95% confidence interval 1.67-6.92, p = 0.001), while the middle albumin group showed no difference (odds ratio 1.74, 95% confidence interval 0.80-3.77, p = 0.162). Neither serum albumin level (as a continuous variable) nor albumin categories were related to AD-CM, AD-CT, or WMH volume. CONCLUSIONS: Low serum albumin may increase the risk of AD dementia by elevating amyloid accumulation. In terms of AD prevention, more attention needs to be paid to avoid a low serum albumin level, even within the clinical normal range, by clinicians.

Sex-Specific Association of Lifetime Body Mass Index with Alzheimer's Disease Neuroimaging Biomarkers.

BACKGROUND: Although recent studies indicate that the relationship between body mass index (BMI) and Alzheimer's disease (AD) may differ by both sex and age of BMI measurement, little information is available on sex- or age-specific associations between BMI and AD neuropathologies. OBJECTIVE: To examined whether sex-specific BMIs measured at different life-stages (in early adulthood, midlife, and late life) were associated with cerebral amyloid-ß (Aß) deposition and AD-signature region cortical thickness (AD-CT) in cognitively normal (CN) older adults. METHODS: A total of 212 CN subjects aged 60-90 years (females 108, males 104), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessments, [11C] Pittsburgh Compound B positron emission tomography, and brain magnetic resonance imaging. BMIs at different life stages were calculated. Multiple regression analyses were performed separately for either sex. RESULTS: In males, lower early adulthood or midlife BMI was associated with greater cerebral Aß deposition, but late life BMI was not. Lower midlife BMI was associated with reduced AD-CT, but the BMI in early adulthood and late life was not. In females, no significant association was observed between any lifetime BMI and Aß deposition or AD-CT. CONCLUSION: Our results support a male-specific association between BMI prior to late life, and in vivo AD pathologies. Avoiding underweight status early in life may be important to prevent AD dementia in males, but not females.

Midlife Lifestyle Activities Moderate APOE ε4 Effect on in vivo Alzheimer's Disease Pathologies.

This study aimed to investigate whether the midlife cognitive activity and physical activity moderate the relationship between apolipoprotein Eε4 (APOE4) and in vivo Alzheimer's disease (AD) pathologies. In total, 287 non-demented older adults (mean age 72 years) from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer's disease cohort were included. Participants underwent a comprehensive clinical assessment including the evaluation for midlife CA and physical activity, [11C]-Pittsburgh-Compound-B-positron emission tomography (PET), [18F]-fluorodeoxyglucose PET, structural magnetic resonance imaging (MRI), and APOE genotyping. We used linear regression and regression-based mediated-moderation models for statistical analyses. Neither midlife cognitive activity nor physical activity moderated the effect of APOE4 on ß-amyloid (Aß) retention itself. Midlife cognitive activity significantly moderated the effect of APOE4 on hippocampal volume [B (SE) = - 627.580 (252.327), t = -2.488, p = 0.014]: APOE4 carriers had smaller hippocampal volume than non-carriers at relatively high cognitive activity state (p = 0.004), but not at relatively low cognitive activity condition (p = 0.937). Midlife physical activity significantly moderated the effect of Aß retention, which was closely related to APOE4, on AD-signature region cerebral glucose metabolism [AD-CM; B (SE) = 0.004 (0.002), t = 2.030, p = 0.043]: higher Aß accumulation was associated with lower AD-CM in relatively low physical activity condition (p < 0.001), whereas no such association was observed in relatively high physical activity state (p = 0.791). The findings suggest that high midlife cognitive activity may accelerate hippocampal atrophy induced by APOE4, whereas high midlife physical activity may delay AD-related cerebral hypometabolism by weakening the influence of APOE4-associated Aß retention.

Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study.

BACKGROUND: An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aß) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aß deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain. METHODS AND FINDINGS: The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aß positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history. CONCLUSIONS: In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aß deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury.

Neuroticism, conscientiousness, and in vivo Alzheimer pathologies measured by amyloid PET and MRI.

AIM: It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD-related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid-beta (Aß) burden, AD-signature regional neurodegeneration, and white matter hyperintensities (WMH) in non-demented middle- and old-aged adults. METHODS: A total of 397 non-demented participants underwent comprehensive clinical and neuropsychological assessments, 11 C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five-Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness. RESULTS: Neither neuroticism nor conscientiousness was associated with cerebral Aß deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD-signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD-signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aß deposition or WMH were not. CONCLUSION: The present findings suggest that amyloid-independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD.

Coffee intake and decreased amyloid pathology in human brain.

Several epidemiological and preclinical studies supported the protective effect of coffee on Alzheimer's disease (AD). However, it is still unknown whether coffee is specifically related with reduced brain AD pathologies in human. Hence, this study aims to investigate relationships between coffee intake and in vivo AD pathologies, including cerebral beta-amyloid (Aß) deposition, the neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH). A total of 411 non-demented older adults were included. Participants underwent comprehensive clinical assessment and multimodal neuroimaging including [11C] Pittsburgh compound B-positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging scans. Lifetime and current coffee intake were categorized as follows: no coffee or <2 cups/day (reference category) and ≥2 cups/day (higher coffee intake). Lifetime coffee intake of ≥2 cups/day was significantly associated with a lower Aß positivity compared to coffee intake of <2 cups/day, even after controlling for potential confounders. In contrast, neither lifetime nor current coffee intake was not related to hypometabolism, atrophy of AD-signature region, and WMH volume. The findings suggest that higher lifetime coffee intake may contribute to lowering the risk of AD or related cognitive decline by reducing pathological cerebral amyloid deposition.

Normative Data for the Logical Memory Subtest of the Wechsler Memory Scale-IV in Middle-Aged and Elderly Korean People.

OBJECTIVE: The purpose of this study is to identify the demographic variables that are affecting performances on the Logical Memory (LM) subtest included in the Korean version of the Wechsler Memory Scale (WMS)-IV and to provide normative data on the LM subtest for the middle-age and elderly Korean people. METHODS: The participants were 435 non-demented adults aging from 50 to 90 and with the educational level ranging from 0 to 21 years. RESULTS: Age and education were found to be significantly associated with performance on the LM subtest, while gender effect was not statistically significant. Therefore, we stratified the norm blocks by age and education. Age was divided into three groups: 50-59, 60-74, and 75-90 years. Education was stratified into three groups: 0-8 years, 9-12 years, and 13 years or more. CONCLUSION: The normative data provided in the current study are expected to be useful in clinical and research settings to detect or define subtle changes in episodic memory in Korean adults and elderly, and can also be used for cross-cultural comparison of verbal episodic memory performance among elderly populations using different languages.

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.

Corrigendum: Behavioral and Neuroimaging Evidence for Facial Emotion Recognition in Elderly Korean Adults with Mild Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

[This corrects the article DOI: 10.3389/fnagi.2017.00389.].

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.

Suicide Risk in Persons with HIV/AIDS in South Korea: a Partial Test of the Interpersonal Theory of Suicide.

PURPOSE: The high disease burden associated with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is linked to the elevated suicide risk in this population. Informed by the interpersonal theory of suicide, this study examined how and under which conditions depression is related to suicide risk in people living with HIV/AIDS. METHODS: A total of 202 outpatients with HIV/AIDS participated in a cross-sectional and multi-center survey involving four university hospitals in South Korea. This self-reported survey included the Hospital Anxiety and Depression Scale, Interpersonal Needs Questionnaire, and Mini-International Neuropsychiatric Interview suicidality module. RESULTS: Participants' mean age was 48.6 (SD = 13.4) and the majority was male (89.1%). The proportions of those at high, medium, and low suicide risk were 18.5%, 20%, and 15.4%, respectively. Depression was associated with suicide risk directly and indirectly by increasing perceived burdensomeness (PB) and the indirect effect of depression on suicide risk mediated by PB was contingent on the level of thwarted belongingness (TB). PB was associated with suicide risk even after controlling for depression, suggesting its independent effect on suicide risk. CONCLUSIONS: PB and TB are potential mechanisms through which depression is associated with suicide risk, supporting the applicability of the interpersonal theory of suicide to understanding a complex interplay of risk factors in people with HIV/AIDS. Moreover, given the independent association of PB with suicide risk, as well as a protective effect of TB in suicide risk, monitoring and management of these factors should be included in the care of people with HIV/AIDS.

Influence of hypertension on brain amyloid deposition and Alzheimer's disease signature neurodegeneration.

This study aimed to investigate the relationship of hypertension with beta-amyloid (Aß) and neurodegeneration biomarkers of Alzheimer's disease (AD) and the modulating effect of apolipoprotein E-ε4 (APOE4). In total, 259 cognitively normal (CN) and 79 AD dementia older adults received clinical assessments including the evaluation for the presence of hypertension, [11C]-Pittsburgh-compound-B-positron emission tomography, magnetic resonance imaging, and APOE genotyping. We used a clinical stage-specific approach, separately focusing on CN and AD dementia stages. For the CN group, individuals with hypertension showed reduced AD signature cortical thickness compared with those without hypertension. Subsequent subgroup analyses showed that hypertension was associated with reduced AD signature cortical thickness only in APOE4 noncarriers, whereas hypertension was associated with elevated Aß deposition in APOE4 carriers. Meanwhile, regardless of APOE4 status, AD dementia patients with hypertension had significantly lower Aß deposition than those without hypertension. In conclusion, the findings suggest that hypertension contributes to AD primarily through the reduction of brain reserve. In case of APOE4 carriers, however, hypertension seems to additionally facilitate AD process through amyloid-dependent pathway.