PropertyValue
is nif:broaderContext of
nif:broaderContext
is schema:hasPart of
schema:isPartOf
nif:isString
  • Subjects were recruited from the outpatient clinic of Taipei Veterans General Hospital between August 2012 and July 2014. As part of the diagnostic procedure, all patients received a standardized assessment that included dementia history, neuropsychological assessment, laboratory tests and MRI scans. Diagnoses were made during a multidisciplinary consensus meeting. The diagnosis of probable AD followed the clinical criteria for probable AD described by the National Institute on Aging–Alzheimer’s Association [2]. The diagnosis of MCI was made according to the revised 2004 consensus criteria [23]. The cut-off value for a diagnosis of MCI was set to 1.5 SD below the age-adjusted norm for the logical memory test of the Wechsler Memory Scale III (WMS-III)[24]. The logical memory test component of the WMS-III assesses verbal memory by asking the subject to recall two stories immediately following an oral presentation (Part I), and again after a 30-min delay (Part II)[25]. The disease duration was defined as the period between the initial onset of symptom reported by caregiver and the performance of this study. Genomic DNA was isolated from whole blood using the Gentra Puregene kit according to the manufacturer’s protocols (Qiagen, Hilden, Germany). The presence of the ε2, ε3, and ε4 alleles of the APOE gene were determined by assessing the sequences at two SNPs (rs429358 and rs7412) [26, 27]. The APOE4 gene carrier was defined as one of alleles contain ε4 gene. Cognitive function was assessed using standardized tests that included several domains. The Mini-Mental Status Examination (MMSE) was used to assess global cognition. To evaluate the severity of dementia, the Clinical Dementia Rating (CDR) scores and sum of box (CDR-SB) tests were given with the caregiver input [28–30]. To assess memory, we used the delay recall of 12-items memory test [31, 32]. To examine the language function, we used both a modified Boston Naming Test [33]. A category verbal fluency test was used to evaluate both verbal ability and executive control ability. In the verbal fluency test, the subject named as many fruits as possible within 1 minute [34]. A forward and backward digit span test was used to assess attention and working memory domain [35]. Finally, the Neuropsychiatric Inventory (NPI) questionnaire was administered to assess the frequency and severity of BPSD [36–38]. Two NPI subscale scores were used in this study, namely, NPI-agitation and NPI-mood symptoms subscales [8]. The NPI-agitation/aggression subscale score included agitation/aggression, dis-inhibition, irritability/lability and aberrant motor behavior items from NPI. The NPI-mood subscale score included depression, anxiety and irritability/lability items from NPI. Each subscale score was calculated by the sum of the items’ severity multiplied by its duration. All participants received whole-brain MRI scans (GE, 3T DISCOVERY 750) in the clinical assessment. First, trans-axial T2-weighted scans (TR/TE = 1130/80 ms, NEX = 2, voxel size 0.55 x 0.55 x 10 mm3), 3D fluid-attenuated inversion Recovery (FLAIR) images (TR/TE = 6000/126 ms, inversion time 1861 ms, NEX = 1, voxel size 0.56 x 0.56 x 1 mm3), and high-resolution sagittal T1-weighted images (TR/TE = 9.1/3.7 ms, NEX = 1, voxel size 0.5 x 0.5 x 1.0 mm3) were acquired. The image analysis included a visual rating of MTA and PA on the T1-weighted images. T1-weighted images were viewed in the coronal plane, and MTA scores for the left and right hemispheres were given. MTA was rated on a 5-point scale (0 point, absent; 1 point, minimal; 2 points, mild; 3 points, moderate; and 4 points, severe) based on the height of the hippocampal formation and the width of the choroid fissure and the temporal horn [20]. PA was rated on a 4-point scale (0 point, absent; 1 point, mild sulcal widening and mild atrophy; 2 points, substantial widening and substantial atrophy; and 3 points, end-stage atrophy) based on the posterior cingulate and parieto-occipital sulcus and sulci of the parietal lobes and precuneus [19]. Fig 1 demonstrates the moderate atrophy of MTA and PA scores. The mean scores for MTA and PA from both hemispheres were calculated for statistic analysis. White matter hyperintensity (WMH) was evaluated using a scale of age-related white matter change (ARWMC) scale on both axial T2-weighted image and 3D-FLAIR images [39]. The ARWMC scale rates WMH on a 4-points scale (0 point, no lesions; 1 point, focal lesions; 2 points, beginning confluence of lesions; and 3 points, diffuse involvement of the entire region, with or without involvement of U fibers). A total of five locations (frontal, parieto-occipital, temporal, basal ganglia and infratentorium) were assessed and the sum of both left and right hemisphere ARWMC scores in each location were used for further analysis. All the visual rating scores were evaluated by one of the author (Dr. Hsu). To confirm the consistency of the visual rating scores between investigators, the first 24 AD cases were selected to have both the MTA and PA score evaluated by both Dr. Hsu and Prof. Philip Scheltens [20]. The Ethics Committee and Institutional Review Board of Taipei Veterans General Hospital approved the study. The written informed consent was provided by the participants and their next of kin or legally authorized representatives. Figure data removed from full text. Figure identifier and caption: 10.1371/journal.pone.0137121.g001 Illustrating the moderate atrophy of MTA and PA scores.(A). the right side MTA score is 2 and the left side MTA score is 1. (B). the both side of PA score is 2. R: right side. All statistic analyses were performed using SPSS (version 21.0). Independent two sample t-tests and X2 tests were conducted to compare age, gender, neuropsychological tests results, MTA, PA and ARWMC scores between AD and MCI patients. The kappa test was used to assess the inter-rater reliability in visual rating scores. Correlation analysis using Pearson correlation coefficient values was conducted to study the relationship between visual rating scales and age, education, MMSE, CDR-SB and NPI subscales. To assess the relationships between the visual rating scores, cognitive functions and neuropsychiatric symptoms, we used regression analysis with MTA and PA as independent variables, and MMSE, CDR-SB and NPI subscale scores as dependent variables. Age, education, APOE4 gene data and diagnostic group were entered as covariates. Statistic significance was defined as a p-value < 0.01.
rdf:type