Beyond the disconnectivity hypothesis of schizophrenia.

To go beyond the disconnectivity hypothesis of schizophrenia, directed (effective) connectivity was measured between 94 brain regions, to provide evidence on the source of the changes in schizophrenia and a mechanistic model. Effective connectivity (EC) was measured in 180 participants with schizophrenia and 208 controls. For the significantly different effective connectivities in schizophrenia, on average the forward (stronger) effective connectivities were smaller, whereas the backward connectivities tended to be larger. Further, higher EC in schizophrenia was found from the precuneus and posterior cingulate cortex (PCC) to areas such as the parahippocampal, hippocampal, temporal, fusiform, and occipital cortices. These are backward effective connectivities and were positively correlated with the positive symptoms of schizophrenia. Lower effective connectivities were found from temporal and other regions and were negatively correlated with the symptoms, especially the negative and general symptoms. Further, a signal variance parameter was increased for areas that included the parahippocampal gyrus and hippocampus, consistent with the hypothesis that hippocampal overactivity is involved in schizophrenia. This investigation goes beyond the disconnectivity hypothesis by drawing attention to differences in schizophrenia between backprojections and forward connections, with the backward connections from the precuneus and PCC implicated in memory stronger in schizophrenia.

Topographic diversity of structural connectivity in schizophrenia.

The neurobiological heterogeneity of schizophrenia is widely accepted, but it is unclear how mechanistic differences converge to produce the observed phenotype. Establishing a pathophysiological model that accounts for both neurobiological heterogeneity and phenotypic similarity is essential to inform stratified treatment approaches. In this cross-sectional diffusion tensor imaging study, we recruited 77 healthy controls, and 70 patients with DSM-IV diagnosis of schizophrenia. We first confirmed the heterogeneity in structural connectivity by showing a reduced between-individual similarity of the structural connectivity in patients compared to healthy controls. Second, at a system level, we found the diversity of the topographic distribution of the strength of structural connectivity was significantly reduced in patients (P = 7.21 × 10-7, T142 = 5.19 [95% CI: 3.37-7.52], Cohen's d = 0.91), and this affected 65 of the 90 brain regions examined (False Discovery Rate <5%). Third, when topographic diversity was used as a discriminant feature to train a model for classifying patients from controls, it significantly improved the accuracy on an independent sample (T99 = 5.54; P < 0.001). These findings suggest a highly individualized pattern of structural dysconnectivity underlies the heterogeneity of schizophrenia, but these disruptions likely converge on an emergent common pathway to generate the clinical phenotype of the disorder.

MAOA-VNTR Genotype Effects on Ventral Striatum-Hippocampus Network in Alzheimer's Disease: Analysis Using Structural Covariance Network and Correlation with Neurobehavior Performance.

Functional polymorphisms in the promoter region of the monoamine oxidase A (MAOA) gene are associated with brain MAOA activity and transcriptional efficiency in patients with Alzheimer's disease (AD). This study investigated structural covariance networks mediated by MAOA-variable number tandem repeat (VNTR) genotypes in patients with AD, and assessed whether this effect was associated with sex. A total of 193 patients with AD were classified into four genotype groups based on MAOA transcriptional efficiency (female low [L], low-high + high activity groups [LH + H]; male L, male H groups). Structural covariance networks were constructed focusing on triple-network and striatal networks. Covariance strength was analyzed in the four groups, and the genotype and sex main effects and their interactions were analyzed. Significant peak cluster volumes were correlated with neurobehavioral scores to establish the clinical significance. MAOA genotypes mediated the structural covariance strength on the dorsolateral prefrontal cortex (dLPFC)-caudate axis in both sexes, but a higher covariance strength was shown in the female L group and male H group. The independent effect of male sex was related to higher covariance strength in the frontal medial superior region in the dLPFC, dorsal caudate (DC), and ventral superior striatum (VSs) seeds. In contrast, female sex had higher covariance strength in the frontal opercular areas anchored by the dLPFC, DC, and VSs seeds. Topographies showing higher covariance strength with sex interactions were found in the male H group and female L group in the dLPFC supplementary motor axis, DC-SMA, and DC-precentral axis. In our patients with AD, MAOA-VNTR polymorphisms and sex had independent and interactive effects on structural covariance networks, of which the dLPFC-, VSs-, and DC-anchored networks represented major endophenotypes that determined cognitive outcomes. The sex-genotype interaction model suggested that male high activity and female low activity may modulate brain morphometric connectivity and determine cognitive scores.

Nonlinear pattern of the emergence of white matter hyperintensity in healthy Han Chinese: an adult lifespan study.

White matter hyperintensities (WMHs) are prevalent in the older adult and are often accompanied by cognitive decline and an increased risk of dementia. However, the roles of WMHs in the periventricular white matter and deep white matter regions in the aging process remain controversial. This study aimed to investigate the WMH burden across the adult lifespan and determine the interrelationships among age, WMH, and cognition. The present study included 312 healthy individuals aged 21-89 years who received structural magnetic resonance imaging and cognitive assessments. Periventricular WMH (PVWMH) and deep WMH (DWMH) volumes were computed and fitted using different regression models to evaluate the trajectory of WMH changes across the lifespan. Our findings support that the changes in WMH volume in the healthy population follow a nonlinear pattern with age, especially in PVWMH. With 2-mediator mediation analysis, we further suggest that the effect of age on the cognitive performance is mediated only by PVWMH. Conclusively, the increased PVWMH, but not DWMH, plays a major role in predicting cognitive aging in healthy adults.

Catechol-O-Methyltransferase Val158Met Polymorphism on Striatum Structural Covariance Networks in Alzheimer's Disease.

The catechol-O-methyltransferase enzyme metabolizes dopamine in the prefrontal axis, and its genetic polymorphism (rs4680; Val158Met) is a known determinant of dopamine signaling. In this study, we investigated the possible structural covariance networks that may be modulated by this functional polymorphism in patients with Alzheimer's disease. Structural covariance networks were constructed by 3D T1 magnetic resonance imaging. The patients were divided into two groups: Met-carriers (n = 91) and Val-homozygotes (n = 101). Seed-based analysis was performed focusing on triple-network models and six striatal networks. Neurobehavioral scores served as the major outcome factors. The role of seed or peak cluster volumes, or a covariance strength showing Met-carriers > Val-homozygotes were tested for the effect on dopamine. Clinically, the Met-carriers had higher mental manipulation and hallucination scores than the Val-homozygotes. The volume-score correlations suggested the significance of the putaminal seed in the Met-carriers and caudate seed in the Val-homozygotes. Only the dorsal-rostral and dorsal-caudal putamen interconnected peak clusters showed covariance strength interactions (Met-carriers > Val-homozygotes), and the peak clusters also correlated with the neurobehavioral scores. Although the triple-network model is important for a diagnosis of Alzheimer's disease, our results validated the role of the dorsal-putaminal-anchored network by the catechol-O-methyltransferase Val158Met polymorphism in predicting the severity of cognitive and behavior in subjects with Alzheimer's disease.

Bidirectional association between Bell's palsy and anxiety disorders: A nationwide population-based retrospective cohort study.

OBJECTIVE: Bell's palsy and anxiety disorders share numerous risk factors (e.g., immune response, ischemia, and psychological stress). However, there have been no studies on the bidirectional temporal association between the two illnesses. In this study, we used the Taiwan National Health Insurance Research Database (NHIRD) to test the bidirectional association between Bell's palsy and anxiety disorders. We hypothesized that patients with Bell's palsy would have an increased risk of subsequent anxiety disorders later in life and that, conversely, those with anxiety disorders would have an increased likelihood of developing Bell's palsy later in life. METHODS: We conducted two retrospective cohort studies using Taiwan's National Health Insurance Research Database (NHIRD). Study 1 included 8070 patients diagnosed with anxiety disorders and 32,280 controls without anxiety disorders who were matched with sex, age, and enrollment date to analyze the following risk of Bell's palsy among both groups. Study 2 included 4980 patients with Bell's palsy and 19,920 controls without Bell's palsy who were matched with sex, age, and enrollment date to analyze the following risk of anxiety disorders among both groups. The patient records selected for the studies were dated between January 1, 2000, and December 31, 2004. All subjects were observed until their outcomes of interest, death or December 31, 2009. RESULTS: After adjustment for age, sex, comorbidities, urbanization, and income, the hazard ratio (HR) for patients with anxiety disorders to contract Bell's palsy was 1.53 (95% CI, 1.21-1.94, P<.001), and the HR for patients with Bell's palsy to develop an anxiety disorder was 1.59 (95% CI, 1.23-2.06, P<.001). CONCLUSION: This study found a bidirectional temporal association between Bell's palsy and anxiety disorders. After one of these conditions develops, the morbidity rate for the other significantly increases. Additional studies are required to determine whether these two conditions share the same pathogenic mechanisms, and whether successfully treating one will reduce the morbidity rate for the other.

Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease.

BACKGROUND: Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. METHODS: We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. RESULTS: There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. CONCLUSIONS: Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.

Geriatric Suicide Attempt and Risk of Subsequent Dementia: A Nationwide Longitudinal Follow-up Study in Taiwan.

OBJECTIVE: It was unclear whether older people without dementia who attempted suicide were at increased risk of subsequently developing dementia. METHODS: Using the Taiwan National Health Insurance Research Database, 1,189 patients aged ≥ 65 years who attempted suicide and 4,756 age- and sex-matched control subjects were enrolled in our study and followed to the end of 2011. Those who developed dementia during the follow-up were identified. RESULTS: Cox regression analysis, after adjusting for demographic data and medical comorbidities, found that geriatric suicide attempt was associated with an increased risk of subsequent dementia (HR: 7.40; 95% CI: 6.11-8.97; Wald χ2 = 414.87, df = 1, p < 0.001). Both patients aged between 65 and 79 years (HR: 7.74; 95% CI: 6.17-9.71; Wald χ2 = 312.62, df = 1, p < 0.001) and patients aged ≥ 80 years (HR: 6.94; 95% CI: 4.73-10.17; Wald χ2 = 97.78, df = 1, p < 0.001) who attempted suicide had an increased risk of developing dementia in later life. CONCLUSION: The elderly who attempted suicide were prone to developing dementia in later life, independent of depression and medical comorbidities. Further studies are necessary to clarify the underlying mechanisms between geriatric suicide and dementia and whether the prompt intervention for geriatric suicide may reduce this risk.

The Association of Aging with White Matter Integrity and Functional Connectivity Hubs.

Normal aging is associated with reduced cerebral structural integrity and altered functional brain activity, yet the association of aging with the relationship between structural and functional brain changes remains unclear. Using combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) modalities, we hypothesized that aging-related changes in white matter integrity (i.e., fractional anisotropy) was associated with the short- or long-range functional connectivity density (FCD) in hub regions. We tested this hypothesis by using a healthy aging cohort comprised of 140 younger adults aged 20-39 years and 109 older adults aged 60-79 years. Compared with the younger group, older adults exhibited widespread reductions in white matter integrity with selective preservation in brain stem tracts and the cingulum connected to the hippocampus and cingulate cortex, whereas FCD mapping in older adults showed a reduced FCD in the visual, somatosensory, and motor functional networks and an increased FCD in the default mode network. The older adults exhibited significantly increased short- or long-range FCD in functional hubs of the precuneus, posterior, and middle cingulate, and thalamus, hippocampus, fusiform, and inferior temporal cortex. Furthermore, DTI-fMRI relationship were predominantly identified in older adults in whom short- and long-range FCD in the left precuneus was negatively correlated to structural integrity of adjacent and nonadjacent white matter tracts, respectively. We also found that long-range FCD in the left precuneus was positively correlated to cognitive function. These results support the compensatory hypothesis of neurocognitive aging theory and reveal the DTI-fMRI relationship associated with normal aging.

Risk of depressive disorders following sudden sensorineural hearing loss: A nationwide population-based retrospective cohort study.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) occurs as an unexplained, rapid loss of hearing that can cause significant stress in the affected individual. This study aims to assess the risk of depressive disorders in SSNHL patients. METHODS: From the National Health Insurance Research Database (NHIRD) in Taiwan, we identified new SSNHL patients diagnosed by an otolaryngologist between January 01, 2000, and December 31, 2008. A control group was composed of individuals who had never suffered from SSNHL. A total of 1717 SSNHL patients and 6868 individuals without SSNHL who were matched by sex, age and index date were followed until December 31, 2009, unless otherwise diagnosed with depressive disorders by a psychiatrist or deceased. RESULTS: The results found that after adjusting for patients' age, sex, comorbidities, urbanization, and monthly income, SSNHL patients are 2.17 times more at risk (95% confidence interval [CI], 1.51-3.08, p<.001) for depressive disorders then control patients, especially in younger age groups (<60 years old). CONCLUSIONS: Our study indicated an increased risk of developing depressive disorders in patients with SSNHL, particularly for younger patients. Symptoms of depression should be regularly evaluated in patients with SSNHL.

Effect of Alzheimer's Disease Risk Variant rs3824968 at SORL1 on Regional Gray Matter Volume and Age-Related Interaction in Adult Lifespan.

Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a SORL1 single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of SORL1 rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between SORL1 rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21-92 years). Through voxel-based morphometry, we found that participants carrying SORL1 allele A exhibited significantly smaller GM volumes in the right posterior cingulate, left middle occipital, medial frontal, and superior temporal gyri. Considerable interaction between age and SORL1 suggested a detrimental and accelerated ageing effect of allele A on putamen. These findings provide evidence that SORL1 rs3824968 modulates regional GM volume and is associated with brain trajectory during the adult lifespan.

Decreased resting-state brain activity complexity in schizophrenia characterized by both increased regularity and randomness.

Schizophrenia is characterized by heterogeneous pathophysiology. Using multiscale entropy (MSE) analysis, which enables capturing complex dynamics of time series, we characterized MSE patterns of blood-oxygen-level-dependent (BOLD) signals across different time scales and determined whether BOLD activity in patients with schizophrenia exhibits increased complexity (increased entropy in all time scales), decreased complexity toward regularity (decreased entropy in all time scales), or decreased complexity toward uncorrelated randomness (high entropy in short time scales followed by decayed entropy as the time scale increases). We recruited 105 patients with schizophrenia with an age of onset between 18 and 35 years and 210 age- and sex-matched healthy volunteers. Results showed that MSE of BOLD signals in patients with schizophrenia exhibited two routes of decreased BOLD complexity toward either regular or random patterns. Reduced BOLD complexity toward regular patterns was observed in the cerebellum and temporal, middle, and superior frontal regions, and reduced BOLD complexity toward randomness was observed extensively in the inferior frontal, occipital, and postcentral cortices as well as in the insula and middle cingulum. Furthermore, we determined that the two types of complexity change were associated differently with psychopathology; specifically, the regular type of BOLD complexity change was associated with positive symptoms of schizophrenia, whereas the randomness type of BOLD complexity was associated with negative symptoms of the illness. These results collectively suggested that resting-state dynamics in schizophrenia exhibit two routes of pathologic change toward regular or random patterns, which contribute to the differences in syndrome domains of psychosis in patients with schizophrenia.

Association of depression and loneliness with specific cognitive performance in non-demented elderly males.

BACKGROUND: Loneliness and depression are very common in the aged population. Both have negative impacts on cognition in the elderly. The present study aimed to investigate the effect of loneliness and depression on total as well as specific cognitive domains in cognitively normal male subjects. MATERIAL/METHODS: A total of 189 cognitively normal male subjects were recruited and underwent Cognitive Abilities Screening Instrument (CASI) and Wechsler Digit Span Task tests. Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Partial correlation test was used to explore the correlation between loneliness/depression and total as well as specific cognition function, with the controlled factors of age and education. RESULTS: Both depression and loneliness are negatively correlated with global cognitive function as evaluated with CASI (r=-0.227, p=0.002; r=-0.214, p=0.003, respectively). The domains of Attention, Orientation, Abstraction and judgment, and List-generating fluency of cognitive function were specifically associated with loneliness, and the domain of orientation was associated with depression after controlling the factors age and years of education. CONCLUSIONS: Our findings suggest that loneliness and depression may have negative impacts on global and specific domains of cognitive function in non-demented elderly males. Both loneliness and depression should be actively recognized earlier and appropriately treated because they are significant sources of cognitive impairment in the elderly.

Functional Connectivity Density Mapping of Depressive Symptoms and Loneliness in Non-Demented Elderly Male.

BACKGROUND: Depression and loneliness are prevalent and highly correlated phenomena among the elderly and influence both physical and mental health. Brain functional connectivity changes associated with depressive symptoms and loneliness are not fully understood. METHODS: A cross-sectional functional MRI study was conducted among 85 non-demented male elders. Geriatric depression scale-short form (GDS) and loneliness scale were used to evaluate the severity of depressive symptoms and loneliness, respectively. Whole brain voxel-wise resting-state functional connectivity density (FCD) mapping was performed to delineate short-range FCD (SFCD) and long-range FCD (LFCD). Regional correlations between depressive symptoms or loneliness and SFCD or LFCD were examined using general linear model (GLM), with age incorporated as a covariate and depressive symptoms and loneliness as predictors. RESULTS: Positive correlations between depressive symptoms and LFCD were observed in left rectal gyrus, left superior frontal gyrus, right supraorbital gyrus, and left inferior temporal gyrus. Positive correlations between depressive symptoms and SFCD were observed in left middle frontal gyrus, left superior frontal gyrus, bilateral superior medial frontal gyrus, left inferior temporal gyrus, and left middle occipital region. Positive correlations between SFCD and loneliness were centered over bilateral lingual gyrus. CONCLUSION: Depressive symptoms are associated with FCD changes over frontal and temporal regions, which may involve the cognitive control, affective regulation, and default mode networks. Loneliness is associated with FCD changes in bilateral lingual gyri that are known to be important in social cognition. Depressive symptoms and loneliness may be associated with different brain regions in non-demented elderly male.

Sleep apnea and the subsequent risk of breast cancer in women: a nationwide population-based cohort study.

BACKGROUND: Hypoxia plays an important role in the development of solid tumors. Intermittent hypoxia is the hallmark of sleep apnea (SA). We tested the hypothesis that SA may increase the risk of breast cancer in Taiwan by using a population-based data set. METHODS: Our study cohort consisted of women diagnosed with SA between January 2003 and December 2005 (n = 846). For each SA patient, five age-matched control women were randomly selected as the comparison cohort (n = 4230). All participant cases were followed for 5 years from the index date to identify the development of breast cancer. Cox proportional-hazards regression was performed to evaluate the 5-year breast-cancer-free survival rates. RESULTS: Forty-four women developed breast cancer during the 5-year follow-up period, among whom 12 were SA patients and 32 were in the comparison cohort. The adjusted hazard ratio (HR) of breast cancer in patients with SA was higher [HR, 2.09; 95% confidence interval (CI), 1.06-4.12; P < 0.05] than that of the controls during the 5-year follow-up. Despite not meeting statistical significance, we found increases in the risk of breast cancer in women aged 30-59 years (HR, 2.06; 95% CI, 0.90-4.70) and ≥60 years (HR, 3.05; 95% CI, 0.90-10.32) compared with those aged 0-29 years. CONCLUSION: The findings of our population-based study suggest an association between SA and an increased risk of breast cancer in women.

Osteoporosis and the risk of symptomatic nephrolithiasis: a population-based 5-year follow-up study in Taiwan.

This study estimates the risk of symptomatic nephrolithiasis within 5 years of newly diagnosed osteoporosis in a Taiwan population. This cohort study consisted of patients with a diagnosis of osteoporosis between Jan. 2003 and Dec. 2005 (N = 1634). Four age- and gender- matched patients for every patient in the study cohort were selected using random sampling as the comparison cohort (N = 6536). All patients were tracked for 5 years from the date of cohort entry to identify whether they developed symptomatic nephrolithiasis. Cox proportional hazard regressions were performed to evaluate the 5-year nephrolithiasis-free survival rates. During the 5-year follow-up period, 60 osteoporosis patients (3.7%) and 165 non- osteoporosis patients (2.5%) developed symptomatic nephrolithiasis. The adjusted HR of symptomatic nephrolithiasis was 1.38 times greater risk for patients with osteoporosis than for the comparison cohort (95% confidence interval (CI) 1.03-1.86; P < .05). Osteoporosis is very likely to be an independent risk factor for subsequent diagnosis of symptomatic nephrolithiasis.

The association of RAB18 gene polymorphism (rs3765133) with cerebellar volume in healthy adults.

Genetic factors are responsible for the development of the human brain. Certain genetic factors are known to increase the risk of common brain disorders and affect the brain structure. Therefore, even in healthy people, these factors have a role in the development of specific brain regions. Loss-of-function mutations in the RAB18 gene (RAB18) cause Warburg Micro syndrome, which is associated with reduced brain size and deformed brain structures. In this study, we hypothesized that the RAB18 variant might influence regional brain volumes in healthy people. The study participants comprised 246 normal volunteers between 21 and 59 years of age (mean age of 37.8 ± 12.0 years; 115 men, 131 women). Magnetic resonance imaging (MRI) and genotypes of RAB18 rs3765133 were examined for each participant. The differences in regional brain volumes between T homozygotes and A-allele carriers were tested using voxel-based morphometry. The results showed that RAB18 rs3765133 T homozygote group exhibited larger gray matter (GM) volume in the left middle temporal and inferior frontal gyrus of the cerebrum than the A-allele carriers. An opposite effect was observed in both the posterior lobes and right tonsil of the cerebellum, in which the GM volume of RAB18 rs3765133 T homozygotes was smaller than that of the A-allele carriers (all P FWE < 0.05). Our findings suggest that RAB18 rs3765133 polymorphism affects the deve-lopment of specific brain regions, particularly the cerebellum, in healthy people.

APOE ɛ4 polymorphism and cognitive deficit among the very old Chinese veteran men without dementia.

Apolipoprotein E (APOE) gene polymorphism has been reported to be associated with cognitive dysfunction in healthy individuals, however the results were controversial in the very old elderly. The aim of this study is to assess the possible association of the APOE polymorphism with cognitive dysfunction in people aged 75 years and over. Four hundred and twenty-five aged Chinese veteran men without dementia were enrolled for APOE genotyping and neuropsychological tests including Mini-Mental Status Examination (MMSE), Digit Span Forward and Backward, and Cognitive Ability Screening Instrument Chinese language version (CASI C-2.0) were evaluated in these subjects. Among the elderly veterans, people who carry APOE ɛ4 were found to have worse performance on the total CASI scores, the abstraction/judgment subscores and the list-generating fluency subscores. This study suggests that the APOE ɛ4 alleles contributed detrimental effects on cognitive function in the very old veterans who do not have dementia.