ABSTRACT
Background: We previously demonstrated the validity of a regression model that included ethnicity as a novel predictor for predicting normative brain volumes in old age. The model was optimized using brain volumes measured with a standard tool FreeSurfer. Objective: Here we further verified the prediction model using newly estimated brain volumes from Neuro I, a quantitative brain analysis system developed for Korean populations. Methods: Lobar and subcortical volumes were estimated from MRI images of 1,629 normal Korean and 786 Caucasian subjects (age range 59-89) and were predicted in linear regression from ethnicity, age, sex, intracranial volume, magnetic field strength, and scanner manufacturers. Results: In the regression model predicting the new volumes, ethnicity was again a substantial predictor in most regions. Additionally, the model-based z-scores of regions were calculated for 428 AD patients and the matched controls, and then employed for diagnostic classification. When the AD classifier adopted the z-scores adjusted for ethnicity, the diagnostic accuracy has noticeably improved (AUCâ=â0.85, ΔAUCâ=â+â0.04, Dâ=â4.10, pâ<â0.001). Conclusions: Our results suggest that the prediction model remains robust across different measurement tool, and ethnicity significantly contributes to the establishment of norms for brain volumes and the development of a diagnostic system for neurodegenerative diseases.
Subject(s)
Alzheimer Disease , Brain , Magnetic Resonance Imaging , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease/ethnology , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Alzheimer Disease/diagnosis , Asian People , Brain/diagnostic imaging , Brain/pathology , Organ Size , White People , East Asian PeopleABSTRACT
The diagnosis of Alzheimer's disease (AD) needs to be improved. We investigated if hippocampal subfield volume measured by structural imaging, could supply information, so that the diagnosis of AD could be improved. In this study, subjects were classified based on clinical, neuropsychological, and amyloid positivity or negativity using PET scans. Data from 478 elderly Korean subjects grouped as cognitively unimpaired ß-amyloid-negative (NC), cognitively unimpaired ß-amyloid-positive (aAD), mild cognitively impaired ß-amyloid-positive (pAD), mild cognitively impaired-specific variations not due to dementia ß-amyloid-negative (CIND), severe cognitive impairment ß-amyloid-positive (ADD+) and severe cognitive impairment ß-amyloid-negative (ADD-) were used. NC and aAD groups did not show significant volume differences in any subfields. The CIND did not show significant volume differences when compared with either the NC or the aAD (except L-HATA). However, pAD showed significant volume differences in Sub, PrS, ML, Tail, GCMLDG, CA1, CA4, HATA, and CA3 when compared with the NC and aAD. The pAD group also showed significant differences in the hippocampal tail, CA1, CA4, molecular layer, granule cells/molecular layer/dentate gyrus, and CA3 when compared with the CIND group. The ADD- group had significantly larger volumes than the ADD+ group in the bilateral tail, SUB, PrS, and left ML. The results suggest that early amyloid depositions in cognitive normal stages are not accompanied by significant bilateral subfield volume atrophy. There might be intense and accelerated subfield volume atrophy in the later stages associated with the cognitive impairment in the pAD stage, which subsequently could drive the progression to AD dementia. Early subfield volume atrophy associated with the ß-amyloid burden may be characterized by more symmetrical atrophy in CA regions than in other subfields. We conclude that the hippocampal subfield volumetric differences from structural imaging show promise for improving the diagnosis of Alzheimer's disease.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Magnetic Resonance Imaging , Hippocampus/diagnostic imaging , Hippocampus/pathology , Atrophy/pathology , Amyloid beta-Peptides , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathologyABSTRACT
OBJECTIVE: Baseline amyloid burden in mild cognitive impairment (MCI) has been linked to conversion to Alzheimer's disease (AD), but the comparison of baseline and longitudinal changes in amyloid burden for predicting AD remains unresolved. The objectives of this study aimed to compare the prognostic ability of baseline and longitudinal changes in amyloid burden in MCI patients. METHODS: Seventy-five individuals with MCI were recruited and examined annually by clinical interviews for a mean follow-up of 24 months (range, 11.6-42.0). [18F]Florbetaben positron emission tomography (PET) scans were performed. T1-weighted 3D volumes were acquired for co-registration, and to define regions of interest. We examined whether baseline and longitudinal amyloid burden changes can improve AD conversion by Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Cox proportional hazards model analysis showed that baseline amyloid burden was significantly associated with increased risk of conversion to AD (hazard ratio [HR]=10.0; 95% confidence interval [CI], 1.15-85.39; p=0.04), but longitudinal amyloid burden changes was not (HR=0.2; 95% CI, 0.02-1.18; p=0.07). When predicting AD, longitudinal amyloid burden changes had better ROC accuracy of 65.2% (95% CI, 48.4-82.0) than baseline amyloid burden of 59.6% (95% CI, 40.3-79.0), without statistical significance in pairwise comparison. CONCLUSION: A single baseline amyloid PET could be sufficient in the prediction of AD conversion in MCI.
ABSTRACT
Brain aging is becoming an increasingly important topic, and the norms of brain structures are essential for diagnosing neurodegenerative diseases. However, previous studies of the aging brain have mostly focused on Caucasians, not East Asians. The aim of this paper was to examine ethnic differences in the aging process of brain structures or to determine to what extent ethnicity affects the normative values of lobar and subcortical volumes in clinically normal elderly and the diagnosis in multi-racial patients with Alzheimer's disease (AD). Lobar and subcortical volumes were measured using FreeSurfer from MRI data of 1,686 normal Koreans (age range 59-89) and 851 Caucasian, non-Hispanic subjects in the ADNI and OASIS datasets. The regression models were designed to predict brain volumes, including ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and MRI scanner manufacturers as independent variables. Ethnicity had a significant effect for all lobar (|ß| > 0.20, p < 0.001) and subcortical regions (|ß| > 0.08, p < 0.001) except left pallidus and bilateral ventricles. To demonstrate the validity of the z-score for AD diagnosis, 420 patients and 420 normal controls were selected evenly from the Korean and Caucasian datasets. The four validation groups divided by race and diagnosis were matched on age and sex using a propensity score matching. We analyzed whether and to what extent the ethnicity adjustment improved the diagnostic power of the logistic regression model that was built using the only z-scores of six regions: bilateral temporal cortices, hippocampi, and amygdalae. The performance of the classifier after ethnicity adjustment was significantly improved compared with the classifier before ethnicity adjustment (ΔAUC = 0.10, D = 7.80, p < 0.001; AUC comparison test using bootstrap). Korean AD dementia patients may not be classified by Caucasian norms of brain volumes because the brain regions vulnerable to AD dementia are bigger in normal Korean elderly peoples. Therefore, ethnicity is an essential factor in establishing normative data for regional volumes in brain aging and applying it to the diagnosis of neurodegenerative diseases.
ABSTRACT
BACKGROUND AND PURPOSE: Although two white matter hyperintensity (WMH) probability maps of healthy older adults already exist, they have several limitations in representing the distribution of WMH in healthy older adults, especially Asian older adults. We constructed and validated a WMH probability map (WPM) of healthy older Koreans and examined the age-associated differences of WMH. METHODS: We constructed WPM using development dataset that consisted of high-resolution 3D fluid-attenuated inversion recovery images of 5 age groups (60-64 years, 65-69 years, 70-74 years, 75-79 years, and 80+ years). Each age group included 30 age-matched men and women each. We tested the validity of the WPM by comparing WMH ages estimated by the WPM and the chronological ages of 30 healthy controls, 30 hypertension patients, and 30 S patients. RESULTS: Older age groups showed a higher volume of WMH in both hemispheres (p < 0.001). About 90% of the WMH were periventricular in all age groups. With advancing age, the peak of the distance histogram from the ventricular wall of the periventricular WMH shifted away from the ventricular wall, while that of deep WMH shifted toward the ventricular wall. The estimated WMH ages were comparable to the chronological ages in the healthy controls, while being higher than the chronological ages in hypertension and stroke patients. CONCLUSIONS: This WPM may serve as a standard atlas in research on WMH of older adults, especially Asians.
Subject(s)
Stroke , White Matter , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Probability , Republic of Korea , White Matter/diagnostic imagingABSTRACT
[This corrects the article DOI: 10.3389/fnagi.2020.00233.].
ABSTRACT
The aging of the brain is a well-investigated topic, but existing analyses have mainly focused on Caucasian samples. To investigate brain aging in East Asians, we measured cortical and subcortical volumes from magnetic resonance imaging (MRI) scans of 1,008 cognitively normal elderly Koreans from the Gwangju Alzheimer's and Related Dementia cohort and 342 Caucasians from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. To determine whether the aging effect varies with ethnicity and sex, beta coefficients of age and confidence intervals (CIs) were estimated in each ethnicity-sex group using a bootstrap method and a regression analysis using the relative volume to intracranial volume as predicted. The betas or aging slopes largely were not significantly different between ethnicity and sex groups in most types of brain structures. However, ethnic differences between the two female groups were found in the brain, most cortical regions, and a few subcortical regions. Ethnic differences in brain aging are likely due in large part to genetic factors; thus, we compared carriers and non-carriers of a gene relevant to longevity and neurodegenerative diseases, such as apolipoprotein E (APOE) ε4. The regions with ethnic differences in women also showed significant differences between Korean APOE ε4 non-carriers and Caucasian APOE ε4 carriers. Furthermore, Caucasian women showed significant APOE ε4 effects in the largest number of regions. These results illustrate that much of the ethnic differences in females may be explained by synergistic effects of ethnic background and APOE ε4 carrier status. Our results suggest that sex-dependent differences of aging between ethnic backgrounds may be due to ethnicity-dependent effects of genetic risk factors, such as APOE ε4. We also presented the normative information on volume estimates of the brain structures of the elderly Korean people in the subdivided age groups. This normative information of the aging brain stratified by ethnicity provides the age-related reference ranges quantified to replace visual judgment and facilitate precise clinical decision-making.
ABSTRACT
Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
ABSTRACT
A test of Jensen effects is of nil value as a diagnostic instrument when various good-sized meta-analyses show Jensen effects appear for both genetic effects and environmental effects. Using thought experiments, Flynn (2019) claims that some schooling gains yield Jensen effects, which should not be the case for an environmental effect. However, a meta-analysis (K = 12, total N = 60,993, mean r = 0.13) of schooling gains shows no Jensen effect. Real data trump thought experiments, so it is concluded there is no empirical proof of anomalous Jensen effects for schooling gains.
Subject(s)
Educational Measurement , Educational Status , Humans , Republic of Korea , Young AdultABSTRACT
Spearman's hypothesis tested at the subtest level of an IQ battery states that differences between races on the subtests of an IQ battery are a function of the g loadings of these subtests, such that there are small differences between races on subtests with low g loadings and large differences between races on subtests with high g loadings. Jensen (1998) stated that Spearman's hypothesis is a law-like phenomenon. It has also been confirmed many times at the level of items of the Raven's Progressive Matrices. This study hypothesizes that with concern to Spearman's hypothesis, subtests and items function in fundamentally the same way, and tested whether Spearman's hypothesis is confirmed at the item level for White-East Asian comparisons. A group of Korean young adults (N=205) was compared with other groups of young adults from Canada, the US, Russia, Peru and South Africa (total N=4770) who took the Advanced Progressive Matrices. Spearman's hypothesis was strongly confirmed with a sample-size-weighted r with a value of 0.63. Computing the g loadings of the items of the Raven with either the Raven-g or the Wechsler-g led to the same conclusions. Tests of Spearman's hypothesis yielded less-strong outcomes when the 36-item Advanced Progressive Matrices were used than when the 60-item Standard Progressive Matrices were used. There is a substantial correlation between sample size and the outcome of Spearman's hypothesis. So, all four hypotheses were confirmed, showing that a part of the subtest-level nomological net replicates at the item level, strengthening the position that, with concern to Spearman's hypothesis, subtests and items function fundamentally the same. It is concluded that Spearman's hypothesis is still a law-like phenomenon. Detailed suggestions for follow-up research are made.
Subject(s)
Cross-Cultural Comparison , Intelligence Tests/statistics & numerical data , Female , Humans , Korea , Male , Psychometrics/statistics & numerical data , Social Environment , Statistics, Nonparametric , Young AdultABSTRACT
BACKGROUND: Being a carrier of the apolipoprotein E (APOE) ε4 allele is a clear risk factor for development of Alzheimer's disease (AD). On some neurocognitive tests, there are smaller differences between carriers and noncarriers, while other tests show larger differences. AIMS: We explore whether the size of the difference between carriers and noncarriers is a function of how well the tests measure general intelligence, so whether there are Jensen effects. METHODS: We used the method of correlated vectors on 441 Korean older adults at risk for AD and 44 with AD. RESULTS: Correlations between APOE carriership and test scores ranged from -.05 to .11 (normal), and -.23 to .54 (AD). The differences between carriers and noncarriers were Jensen effects: r = .31 and r = .54, respectively. CONCLUSION: A composite neurocognitive score may show a clearer contrast between APOE carriers and noncarriers than a large number of scores of single neurocognitive tests.
Subject(s)
Alzheimer Disease/genetics , Apolipoprotein E4/genetics , Cognitive Dysfunction/genetics , Neuropsychological Tests/statistics & numerical data , Aged , Female , Genotype , Humans , Male , Republic of Korea , Risk FactorsABSTRACT
A fundamental theoretical question in intelligence research is to what extent the g factor and heritability coefficients of the subtests of an IQ battery are correlated. Five studies from Western countries showed modest to strong positive correlations (range = .43-.77), and six studies from a Japanese meta-analysis showed zero to modest correlations (range = -0.01-0.59). The Western and Japanese studies were compared with a Korean sample of 24 monozygotic and 20 dizygotic young adult twin pairs administered the Korean Wechsler Adult Intelligence Scale-Revised (WAIS-R). A univariate twin model was applied to all subscale scores leading to estimates of heritability for all scales. g loadings were also computed using principal-axis factor analysis. Finally, the correlation between the heritabilities and the g loadings of these scales were computed. The correlations of r = -.15 were not in line with previous studies. It could be that Spearman's hypothesis is less strongly confirmed for Northeast Asians, but it is also possible that the study will be an outlier in a future meta-analysis. More primary research and a meta-analysis of all studies are needed.
Subject(s)
Intelligence/genetics , Twins , Wechsler Scales/statistics & numerical data , Adult , Female , Humans , Male , Republic of Korea , Young AdultABSTRACT
BACKGROUND: Cortical features derived from magnetic resonance imaging (MRI) provide important information to account for human intelligence. Cortical thickness, surface area, sulcal depth, and mean curvature were considered to explain human intelligence. One region of interest (ROI) of a cortical structure consisting of thousands of vertices contained thousands of measurements, and typically, one mean value (first order moment), was used to represent a chosen ROI, which led to a potentially significant loss of information. METHODS: We proposed a technological improvement to account for human intelligence in which a second moment (variance) in addition to the mean value was adopted to represent a chosen ROI, so that the loss of information would be less severe. Two computed moments for the chosen ROIs were analyzed with partial least squares regression (PLSR). Cortical features for 78 adults were measured and analyzed in conjunction with the full-scale intelligence quotient (FSIQ). RESULTS: Our results showed that 45% of the variance of the FSIQ could be explained using the combination of four cortical features using two moments per chosen ROI. Our results showed improvement over using a mean value for each ROI, which explained 37% of the variance of FSIQ using the same set of cortical measurements. DISCUSSION: Our results suggest that using additional second order moments is potentially better than using mean values of chosen ROIs for regression analysis to account for human intelligence.
Subject(s)
Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Intelligence/physiology , Adult , Female , Humans , Imaging, Three-Dimensional , Least-Squares Analysis , Magnetic Resonance Imaging , Male , Surface Properties , Young AdultABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder that leads to a decline in cognitive and intellectual abilities and an irreversible mental deterioration. Based on multidisciplinary AD research, the most universally accepted hypotheses on AD pathogenesis are the intracerebral aggregate formation of beta-amyloid (Aß) peptides. According to medical paradigmatic transition from medical treatment to early diagnostic prevention, scientists have considered physiological body fluid as a biomarker medium, in which the promising AD biomarkers could be verified. Recently, use of saliva has been considered as one of the diagnostic fluids over the past decade with meaningful diagnostic potential. We utilized saliva as a biomarker medium to correlate the salivary Aß levels to AD pathological aspects, especially to the mild cognitive impairment group among AD patients, and to verify our detecting system to be sensitive enough for an early diagnostic tool. The identification of the salivary AD biomarkers using a facile microarraying method would motivate this study with the assistance of magnetically assembled antibody-conjugated nanoparticles and a photomultiplier tube as an optical detector. This simple magnetoimmunoassay system measures the photointensity generated by fluorescence, enables the quantification of the Aß peptides from AD salivary samples, and consequently classifies the salivary Aß levels into AD pathological aspects. This method demonstrates a facile approach enabling it to simply detect salivary Aß peptides at a concentration as low as ~20 pg/ml. It is expected that our simple magnetoimmunoassay system may have a potential as a detector for low-level Aß peptides with weak-fluorescence emission.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/analysis , Biomarkers/analysis , Immunoassay/methods , Magnetite Nanoparticles/chemistry , Case-Control Studies , Humans , Microscopy, Fluorescence , Photons , Saliva/chemistryABSTRACT
The global pattern of cortical sulci provides important information on brain development and functional compartmentalization. Sulcal patterns are routinely used to determine fetal brain health and detect cerebral malformations. We present a quantitative method for automatically comparing and analyzing the sulcal pattern between individuals using a graph matching approach. White matter surfaces were reconstructed from volumetric T1 MRI data and sulcal pits, the deepest points in local sulci, were identified on this surface. The sulcal pattern was then represented as a graph structure with sulcal pits as nodes. The similarity between graphs was computed with a spectral-based matching algorithm by using the geometric features of nodes (3D position, depth and area) and their relationship. In particular, we exploited the feature of graph topology (the number of edges and the paths between nodes) to highlight the interrelated arrangement and patterning of sulcal folds. We applied this methodology to 48 monozygotic twins and showed that the similarity of the sulcal graphs in twin pairs was significantly higher than in unrelated pairs for all hemispheres and lobar regions, consistent with a genetic influence on sulcal patterning. This novel approach has the potential to provide a quantitative and reliable means to compare sulcal patterns.
Subject(s)
Algorithms , Brain Mapping/methods , Cerebral Cortex/anatomy & histology , Image Processing, Computer-Assisted/methods , Adolescent , Female , Humans , Magnetic Resonance Imaging , Male , Matched-Pair Analysis , Twins, Monozygotic , Young AdultABSTRACT
Sulcal pits are hypothesized to form early during development and be under tighter genetic control than other regions of the cortex. We investigated the relationship between the presence of sulcal pits and intellectual ability, estimated with the full-scale, verbal, and performance intelligence quotient (IQ), in the brains of 78 healthy young adults. We automatically extracted sulcal pits from magnetic resonance images and developed a method for their automatic labeling. The difference in the number of sulcal pits between high and average IQ groups for each labeled region was statistically analyzed. We found that in the high verbal IQ group a sulcal pit was more frequently present in the left posterior inferior frontal sulcus (70% in the high IQ group vs. 40% in the average IQ group) and the right posterior inferior temporal sulcus (70% vs. 43%), which have been reported to be regions of language function. Greater mean curvature of the deep sulcal areas in these regions was shown for the high verbal IQ group. This provides the complementary morphological information about the presence of more sulcal pits. These findings suggest that factors influencing verbal intelligence may emerge in the language areas early during cortical development and may be under tight genetic control.
Subject(s)
Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Cognition/physiology , Intelligence/physiology , Magnetic Resonance Imaging/methods , Adolescent , Adult , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity , Statistics as Topic , Young AdultABSTRACT
We hypothesized that individual differences in intelligence (Spearman's g) are supported by multiple brain regions, and in particular that fluid (gF) and crystallized (gC) components of intelligence are related to brain function and structure with a distinct profile of association across brain regions. In 225 healthy young adults scanned with structural and functional magnetic resonance imaging sequences, regions of interest (ROIs) were defined on the basis of a correlation between g and either brain structure or brain function. In these ROIs, gC was more strongly related to structure (cortical thickness) than function, whereas gF was more strongly related to function (blood oxygenation level-dependent signal during reasoning) than structure. We further validated this finding by generating a neurometric prediction model of intelligence quotient (IQ) that explained 50% of variance in IQ in an independent sample. The data compel a nuanced view of the neurobiology of intelligence, providing the most persuasive evidence to date for theories emphasizing multiple distributed brain regions differing in function.
Subject(s)
Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Intelligence/physiology , Magnetic Resonance Imaging , Adult , Cerebral Cortex/blood supply , Female , Humans , Male , Models, Neurological , Models, Psychological , Oxygen/blood , Psychometrics , Reproducibility of Results , Thinking/physiologyABSTRACT
General intelligence (g) is a common factor in diverse cognitive abilities and a major influence on life outcomes. Neuroimaging studies in adults suggest that the lateral prefrontal and parietal cortices play a crucial role in related cognitive activities including fluid reasoning, the control of attention, and working memory. Here, we investigated the neural bases for intellectual giftedness (superior-g) in adolescents, using fMRI. The participants consisted of a superior-g group (n = 18, mean RAPM = 33.9 +/- 0.8, >99%) from the national academy for gifted adolescents and the control group (n = 18, mean RAPM = 22.8 +/- 1.6, 60%) from local high schools in Korea (mean age = 16.5 +/- 0.8). fMRI data were acquired while they performed two reasoning tasks with high and low g-loadings. In both groups, the high g-loaded tasks specifically increased regional activity in the bilateral fronto-parietal network including the lateral prefrontal, anterior cingulate, and posterior parietal cortices. However, the regional activations of the superior-g group were significantly stronger than those of the control group, especially in the posterior parietal cortex. Moreover, regression analysis revealed that activity of the superior and intraparietal cortices (BA 7/40) strongly covaried with individual differences in g (r = 0.71 to 0.81). A correlated vectors analysis implicated bilateral posterior parietal areas in g. These results suggest that superior-g may not be due to the recruitment of additional brain regions but to the functional facilitation of the fronto-parietal network particularly driven by the posterior parietal activation.