Previous literature suggests that Alzheimer's disease (AD) process may contribute to late-life onset depression (LLOD). Therefore, we investigated the association of LLOD with cerebral amyloidosis and neuronal injury, the two key brain changes in AD, along with vascular risks. Twenty nine non-demented individuals who first experienced major depressive disorder (MDD) after age of 60 years were included as LLOD subjects, and 27 non-demented elderly individuals without lifetime experience of MDD were included as normal controls (NC). Comorbid mild cognitive impairment (MCI) was diagnosed in 48% of LLOD subjects and in 0% of NC. LLOD, irrespective of comorbid MCI diagnosis, was associated with prominent prefrontal cortical atrophy. Compared to NC, LLOD subjects with comorbid MCI (LLODMCI) showed increased cerebral 11C-Pittsburg compound B (PiB) retention and plasma beta-amyloid 1-40 and 1-42 peptides, as measures of cerebral amyloidosis; and, such relationship was not observed in overall LLOD or LLOD without MCI (LLODwoMCI). LLOD subjects, particularly the LLODwoMCI, had higher systolic blood pressure (SBP) than NC. When analyzed in the same multiple logistic regression model that included prefrontal gray matter (GM) density, cerebral amyloidosis, and SBP as independent variables, only prefrontal GM density showed a significant independent association with LLOD regardless of MCI comorbidity status. Our findings suggest AD process might be related to LLOD via prefrontal neuronal injury in the MCI stage, whereas vascular processes-SBP elevation, in particular-are associated with LLOD via prefrontal neuronal injury even in cognitively intact or less impaired individuals.
Very little is known for the association between lifetime sleep experience and cerebral beta-amyloid protein (Aβ) deposition, which is the core pathological change related to Alzheimer’s disease process. This study aimed to investigate the relationship of hours of sleep and sleep quality in young and middle age-period with cerebral Aβ burden in elderly individuals with normal cognition. One hundred and twenty-two cognitively normal old adults (age range: 60-87 years), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), were included. All subjects underwent comprehensive clinical and neuropsychological assessment, 11C labelled Pittsburgh Compound B (PiB) positron emission tomography (PET). Through structured clinical interview for each participant, mean hours of sleep and sleep quality were assessed for the following age-periods: before 20 years, in their 20-30s, and 40-50s. Current sleep quality was also assessed by using the Pittsburgh Sleep Quality Index (PSQI). Global cerebral Aβ deposition was defined as mean cortical PiB retention of the cortical regions including the frontal, lateral temporal, lateral parietal and precuneus/posterior cingulate cortices. The poorer sleep quality in all the three younger age-periods was associated with higher mean cortical PiB retention even after controlling for age, gender, apolipoprotein E e4 status, and Hamilton Depression Rating Scale score. In contrast, mean hours of sleep in any young or middle age-period or current sleep quality measured by the PSQI were not related to mean cortical PiB retention. These findings suggest that poorer sleep quality, but not hours of sleep, in young and middle age-period may contribute to increased cerebral amyloid burden in old age.
The present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer's disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals. This study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included 11C-Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, 18F-deoxyglucose (FDG)-PET scans, and the quantification of serum triiodothyronine (T3), free T3, free thyroxine (fT4), and TSH levels. All participants were clinically euthyroid. Independent negative associations were found between serum fT4 levels and global cerebral Aβ deposition after controlling for the effects of age, gender, and the apolipoprotein E ε4 (APOEε4) genotype. Although serum TSH levels were not associated with global cerebral Aβ deposition, they had a significant negative association with glucose metabolism in the precuneus/posterior cingulate cortex after controlling for age, gender, and the APOEε4 genotype. No other thyroid hormones exhibited relationships with either brain Aβ burden or glucose metabolism. Even in a clinical euthyroid state, low serum fT4 and high serum TSH levels appear to be differentially associated with AD-specific brain changes.
Ahn, Yong Min; Choi, Hyo Jung; Han, Jae Wook; Jang, Sun Joo; Lyoo, In Kyoon; Kwon, Jun Soo.January, 2013.종합병원 정신건강의학과 낮병원의 역할변천 및 발전 방향 (The role transition and development direction of the psychiatric day hospital in general hospital),Articles,[Seoul, Korea]대한신경정신의학회,9
Although the number of unwed mothers have mental health problems and intellectual disability, little research have focused on their mental and cognitive status. Since there has been public stigma of unwed mother in South Korea, they tend to conceal their status and less likely to seek psychiatric and psychological help. In this context, this study aims to assess current status of their mental health and intellectual characteristics. A total 48 unwed mothers from two shelter homes in South Korea were agreed to participate in the study. To compare mental health and intellectual abilities of unwed mothers with the general women population, reference data from national studies was used. Unwed mothers were more likely to have mood disorder, post traumatic stress disorder(PTSD), alcohol and nicotine use disorder, attention-deficit hyperactivity disorder (ADHD) than the general women population. Among 48 participants, 20 (41.7%) were lower than 70 Intelligence Quotient (IQ) and the mean of IQ (78.31) was significantly lower than normalized IQ mean of general women population. In logistic regression analysis, psychiatric disorders were associated intellectual disability. This study confirmed that unwed mothers dwelling in Korean shelter homes have more experience of mental disorders and lower intellectual ability than general women population.
A couple of studies with small sample size examined the association of blood insulin level and cerebral glucose metabolism (CMglu), but yielded mixed results. Moreover, as those studies adopted experimental design which induced hyperinsulinemia beyond the normal range of fasting blood insulin, it remains unclear which cerebral regions are sensitive to the basal level of fasting blood insulin in nondiabetic individuals. Thus, we tried to identify the brain regions where fasting blood insulin level is associated with CMglu in nondiabetic, cognitively normal (CN) elderly individuals using a voxel-wise analysis of 18F-fluorodeoxyglucose (FDG)-PET. Two-hundred five nondiabetic CN elderly individuals from the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included for analysis. All participants underwent comprehensive clinical and neuropsychological assessment, FDG-PET, magnetic resonance imaging, and blood sampling for overnight fasting blood insulin, fasting blood glucose (FBG) and apolipoprotein E (APOE) genotyping. Vascular risk factors (VRF) other than DM (i.e. hypertension, hyperlipidemia, coronary heart disease, stroke, and transient ischemic attack) were evaluated and VRF score (VRS) was calculated as a sum of the present VRF, reported in percentage. Body mass index (BMI) were also measured. Voxel-wise analysis of FDG-PET was performed using the Statistical Parametric Mapping 12 (SPM12). Significant clusters were reported after multiple comparison correction (p < 0.005, k > 1062 voxels; 3dClustSim). We found significant positive association between fasting blood insulin and CMglu in the several regions including the bilateral fusiform, parahippocampal and inferior temporal regions, left entorhinal area, as well as bilateral inferior parietal regions and medial, orbitofrontal regions after controlling the effect of APOE4 carrier status, VRS, BMI, FBG, and demographic variables (i.e. age, sex, educational years). However, there were no significant regions that showed significant negative association between fasting blood insulin level and CMglu. Our results suggest that basal blood insulin level is closely related to maintaining cerebral glucose metabolism in the specific regions vulnerable to Alzheimer's disease (AD)-related hypometabolism or neurodegeneration.
Previous researches on the late-life onset depression (LLOD) have revealed its association with vascular risk factors, which supported vascular depression hypothesis. However, several recent studies raised the possibility of the role of cerebral amyloidosis in LLOD. We aimed to investigate the independent association of vascular risk factors and cerebral amyloidosis with the experience of LLOD. Twenty eight non-demented subjects who first experienced major depressive episode after age of 60 years were recruited as LLOD patients. Twenty seven non-demented elderly individuals who had no experience of major depressive episode were also included as normal control (NC) subjects. All participants received comprehensive clinical assessment including vascular risk evaluation, 11C labeled Pittsburgh Compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging (MRI). There were no group differences in age, education level but the frequency of female participants was significantly higher in LLOD patients compared to NC subjects. Univariate group comparison demonstrated that LLOD subjects had significantly higher systolic blood pressure than NC. In contrast, no significant between-group differences were found in regard of mean cortical PiB retention, and the frequency of PiB-positive and ApoE e4 carriers. Multiple logistic regression analysis including diagnostic group (LLOD vs. NC) as a dependent variable showed that systolic blood pressure was significantly associated with LLOD diagnostic state after controlling age, education, gender, and mean cortical PiB retention as covariates. Mean cortical PiB retention did not show any significant association with LLOD state in the same regression model. The results suggest that while vascular risk, hypertension in particular, is closely related to LLOD as indicated by vascular depression hypothesis, cerebral amyloidosis per se is probably not a major contributor to LLOD.
Very little is known for the association between lifetime sleep experience and in vivo Alzheimer's disease (AD) pathologies including cerebral beta-amyloid protein (Aβ) deposition and neuronal injury. This study aimed to investigate the relationship of sleep hours and sleep quality in the young adulthood, midlife, and present time with cerebral Aβ burden and neurodegeneration in elderly individuals with normal cognition. Two-hundred two cognitively normal old adults (age range: 60–87 years), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), were included. All subjects underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B (PiB) positron emission tomography (PET), [18F] Fluorodeoxyglucose (FDG)-PET, Magnetic Resonance Imaging(MRI). Through structured interview, mean hours of sleep and sleep quality were assessed for the following age-periods: in their 20–30s, 40–50s, and in a recent one-month. All the analyses were adjusted for age, gender, education, apolipoprotein E e4 status, vascular risk score, Hamilton Depression Rating Scale score, and use of sleep medication. Poorer sleep quality during 40–50s and recent one-month was significantly associated with increased Aβ deposition, and shorter duration of sleep during 40–50s was related to increased AD-signature region neurodegeneration measured by cerebral glucose metabolism. Neither sleep quality nor sleep duration during 20–30s was related to Aβ burden and neurodegeneration. These findings support the importance of midlife sleep for the development of AD, suggesting that poor sleep quality and short sleep hours during midlife may increase cerebral Aβ deposition and neurodegeneration, respectively. The current findings also indicate the possibility of bidirectional relationship between Aβ burden and sleep quality.
This study aimed to identify the functional neuroanatomical correlates of figure copy and recall task performances as measured by the tests in the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) neuropsychological battery and the Benton's Visual Retention Test (BVRT) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Both the CERAD neuropsychological battery and BVRT were administered to 44 patients with amnestic MCI and 26 patients with AD. Regional cerebral glucose metabolism (rCMglc) was measured by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Using statistical parametric mapping 8 (SPM 8), correlations between the test scores and rCMglc were analyzed on a voxel-by-voxel basis. CERAD constructional praxis (geometrical figure copy) scores showed significant positive correlation with rCMglc of the bilateral inferior parietal lobe, left middle and inferior temporal gyrus, left middle frontal gyrus, left insula, right superior parietal lobe, and right precuneus. In contrast, the scores of the BVRT figure copy task (irregular random figure copy) had significant positive correlation predominantly with rCMglc of the right side cortical regions including inferior parietal lobe, superior temporal gyrus, middle and inferior frontal gyrus, and middle and inferior occipital cortices. In terms of recall task performances, while CERAD constructional recall (delayed recall) scores were associated mainly with the metabolism of the right cortical regions such as inferior temporal, middle frontal, and angular gyrus, BVRT recall (immediate recall) scores were correlated predominantly with the metabolism of left side cortical regions including inferior and superior parietal lobe, middle, inferior and superior frontal gyrus, and middle and inferior temporal gyrus. The results suggested that, although classified as similar figure copy and recall task, each test in the CERAD neuropsychological battery has quite different functional neuroanatomical substrates compared to the corresponding test in the BVRT in MCI and AD individuals.
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