Voxel-based morphometry of amnestic mild cognitive impairment and Alzheimer's disease

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Alzheimer’s Imaging Consortium IC-P: Poster Presentations

association between each subtype and its progression to a particular type of dementia still remains open. This study aims to examine the association using a series of clinical data including MRI and SPECT gained from a longitudinal study for up to 6-year observation. Methods: Between 2001 and 2002, we conducted the baseline study and judged the cognitive status for each of the 1888 participants aged 65 yrs and older. The cognitive status included the 4 subtypes of MCI, dementia and normal cognitive function. Among the participants, 286 agreed to join the neuroimaging study. We excluded 2 who were already demented at baseline and 58 who dropped out during the observation period of 6 years. The remaining 226 annually underwent a battery of cognitive tests, MRI and SPECT. We judged the cognitive status, and confirmed the conversion to dementia (based on the DSM-IV). When a converter was detected, we made diagnosis of illness causing dementia. The type of dementia (Alzheimer’s disease; AD, Dementia with Lewy bodies; DLB, Vascular dementia; VaD, Frontotemporal dementia; FTD, and others) was diagnosed on the established clinical criteria. This study was approved by the Ethics Committee of the University of Tsukuba and written informed consent was gained from the subjects. Results: 78 MCI patients(19aMCIs,20aMCIm,25naMCIs,14naMCIm) and 148 subjects with normal cognitive function were followed up. During the observation, we confirmed 47 cases of converter to dementia. The conversion rates for aMCIs, aMCIm, naMCIs, naMCIm and the normal were 32%, 85%, 32%, 43%, and 7%, respectively. The risk of the conversion was significantly higher for aMCIm. Among the converters, AD was the most frequent type of dementia. Conclusions: Different from previous studies,we judged the conversion using neuroimaging as well as cognitive assessment data. We found a higher conversion rate to dementia in general and AD in particular among the individuals with aMCIm. Subtyping of MCIs is useful to a certain extent for predicting development of particular types of dementia. IC-P-018

DIFFUSION TENSOR IMAGING CHARACTERISTICS OF AMNESTIC AND NONAMNESTIC MILD COGNITIVE IMPAIRMENT

Kejal Kantarci, Ramesh T. Avula, Matthew L. Senjem, Ali R. Samikoglu, Maria M. Shiung, Scott A. Przybelski, Stephen D. Weigand, Heidi A. Ward, Prashanthi Vemuri, David S. Knopman, Bradley F. Boeve, Ronald C. Petersen, Clifford R. Jack, Jr., Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: The broad clinical definition of mild cognitive impairment (MCI) includes amnestic MCI (aMCI) with impairment in memory domain and non-amnestic MCI (naMCI) with impairment(s) in cognitive domains other than memory such as attention/executive functioning, language, and visuospatial processing. While people with the aMCI subtype most commonly progress to Alzheimer’s disease (AD), the natural history, imaging characteristics and the pathological underpinnings of naMCI are less clear. Non-invasive imaging markers for underlying pathologies in MCI may be useful in identifying patients who may benefit from disease specific treatments at the prodromal stage of dementia. Diffusion tensor MR imaging (DTI) provides information on the integrity of tissue microstructure. The magnitude of diffusivity measured with the apparent diffusion coefficient (ADC) increases, and the directionality of diffusivity measured with fractional anisotropy (FA) decreases with neurodegeneration.Our objective was to determine the characteristic DTI profiles of the MCI subtypes. Methods: We studied clinically diagnosed age, gender and education matched patients with aMCI (n ¼ 28), naMCI (n ¼ 28), and cognitively normal (CN) (n ¼ 28) at 3Tesla using parallel imaging with an acceleration factor of two. 3D-MPRAGE was performed for anatomical segmentation and labeling. In order to avoid partial volume averaging of tissue diffusivity with CSF, we used an EPI-FLAIR-DTI sequence (which nulls CSF) with 21 diffusion sensitive gradient directions (b ¼ 1000 s/mm2). We measured the ADC from segmented cortical gray matter in regions derived from the automated anatomic labeling atlas. Color FA maps generated in DTIStudio were used for measuring tract-based FA and ADC by manual placement of tract-based regions of interest. Results: Patients with aMCI had elevated ADC in the hippocampus (p < 0.05), and de-

creased posterior cingulum tract FA (p < 0.01) compared to CN subjects. Patients with naMCI had decreased posterior cingulum tract FA (p < 0.01), but normal hippocampal ADC compared to CN subjects. Conclusions: The neurodegenerative pathology of AD involves the hippocampus early during the pathological progression. For this reason, elevated hippocampal ADC most likely represent a high frequency of early AD pathology in aMCI patients. Conversely, finding normal hippocampal ADC on avearge in the naMCI subtype suggest that the underlying pathological substrates may include pathologies other than AD in some proportion of naMCI patients. IC-P-019

VOXEL-BASED MORPHOMETRY OF AMNESTIC MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE

Yi He1,2, Mei-Yan Zhang1,2, Kevin Head3, Daniel Chang3, Huishu Yuan4, Min-Ying Su3, Xin Yu1,2, Huali Wang1,2, 1Peking University Institute of Mental Health, Beijing, China; 2Key Laboratory of Mental Health, Ministry of Health, Beijing, China; 3University of California, Irvine, CA, USA; 4Peking University Third Hospital, Beijing, China. Contact e-mail: heyi0962@ sina.com Background: Amnestic mild cognitive impairment (aMCI) is considered preclinical stage of Alzheimer’s disease (AD). This study aimed to investigate the atrophy pattern in aMCI and AD using optimized voxel-based mophormetry (VBM) technique. Methods: Fourteen subjects meeting aMCI criteria proposed by Petersen (aMCI group), 56 patients with mild AD (NINCDS-ADRDA criteria, AD group), and 16 healthy elderly controls (NC group) with normal-appearing white matter were enrolled in this prospective study. All subjects underwent a comprehensive neuropsychological test and MRI scanning when recruited into DCRC case registry. High-resolution 3D T1 structural images were acquired with 3DMPRAGE sequence (TR ¼ 2530ms,TE ¼ 3.44ms,TI ¼ 1100ms,slice thickness ¼ 1 mm with no gap,FOV ¼ 256 3 256,voxel size ¼ 1 mm 3 1 mm 3 1 mm). All 3D T1 images were analyzed with SPM5 by following the procedures of optimized VBM analysis, including co-registration, modulated, segmentation, and smoothing. Age and gender were used as nuisance variables in the analysis. Results: Compared with control group, there was significant gray matter volumetric reduction in bilateral middle frontal gyrus, superior frontal gyrus, middle temporal gyrus, inferior parietal lobule, superior parietal lobule, inferior temporal gyrus, fusiform gyrus, caudate, left middle frontal gyrus, inferior frontal gyrus, parahippocampal gyrus, precuneus, supramarginal gyrus, thalamas, orbital gyrus and right postcentral lobule, cingulate gyrus, superior temporal gyrus, insula, posterior lobe and paracentral lobule in AD group (PFWE-cor < 0.01, Figure 1) and in right cingulate gyrus in aMCI group (Puncorrected < 0.005). In aMCI group, GM volume was sig-

Alzheimer’s Imaging Consortium IC-P: Poster Presentations nificant more than that in AD group, in bilateral insula, caudate, middle frontal gyrus, superior parietal lobule, left paracentral lobule, sub-gyral and right thalamus, superior temporal gyrus, middle temporal gyrus (PFWE-cor < 0.01, Figure 1). As for the comparison between aMCI and NC groups, there were no significant suprathreshold clusters at the significance level of Puncorrected < 0.005. Conclusions: AD is characterized with significant regional atrophy in temporal, frontal and parietal lobes, and aMCI presents minor atrophy in cingulate gyrus. It is suggested cingulate gyrus may be one of the earliest affected region in the development of Alzheimer’s disease. IC-P-020

3-D MAPPING OF EPISODIC MEMORY AND EXECUTIVE FUNCTION IN LATE-ONSET DEPRESSION

Huali Wang1,2, Na Zhang1,2, Mei-Yan Zhang1,2, Jing Liao3, Daniel Chang4, Huishu Yuan3, Min-Ying Su4, Xin Yu1,2, 1Peking University Institute of Mental Health, Beijing, China; 2Key Laboratory for Mental Health, Ministry of Health, Beijing, China; 3Peking University Third Hospital, Beijing, China; 4University of California, Irvine, CA, USA. Contact e-mail: [email protected] Background: Cognitive impairment and late-life depression (LOD) are associated with increased risk for subsequent dementia. This study aimed to explore the neural correlates of memory performance and executive function in LOD from the structural neuroimaging perspective. Methods: Nine patients with late-onset depression (ICD-10 criteria, LOD group, age ¼ 64.9 6 9.2, male ¼ 4, female ¼ 5, MMSE ¼ 22.7 6 5.5), fourteen subjects meeting aMCI criteria proposed by Petersen (aMCI group, age ¼ 72.6 6 4.9, male ¼ 8, female ¼ 6, MMSE ¼ 26.0 6 1.9), and 16 healthy elderly controls (NC group, age ¼ 69.9 6 2.8, male ¼ 6, female ¼ 10, MMSE ¼ 28.6 6 2.6) with normal-appearing white matter were enrolled in this prospective study. All subjects were administered a set of memory tests, consisting of common object memory test (immediate memory, 5-min delayed recall, 30-min delayed recall) and logical memory (WMS-IIIR). The composite memory score was calculated as the sum of these four test scores. Category fluency test was used to assess the executive function. High-resolution 3D T1 structural images were acquired with 3D-MPRAGE sequence and were analyzed with SPM5 by following optimized voxel-based morphometry (VBM) protocol. The composite memory score and verbal fluency test score were entered as covariates in a general linear model that predict the gray matter density at each voxel. Results: After controlling age and education level, the composite memory scores in LOD and aMCI groups were significantly lower than in NC group (F(4) ¼ 4.79, P ¼ 0.004). The verbal fluency score was significantly lower in LOD group relative to NC group (F(4) ¼ 5.77, P ¼ 0.001). There were no significant difference in composite memory score (P ¼ 0.49) or verbal fluency score (P ¼ 0.201) between LOD and aMCI group. In LOD group, composite memory score correlated strongly with gray matter density in right medial frontal gyrus (r ¼ 0.54, Puncorrected < 0.001, Figure 1A). Strong correlation was also observed between verbal fluency score and gray matter density in right superior temporal gyrus (r ¼ 0.67, Puncorrected < 0.001, Figure 1B). In aMCI and NC groups, there

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was no significant correlation between gray matter density and either composite memory or verbal fluency score. Conclusions: In late-life depression, right frontal lobe is closely linked with memory and right temporal lobe more associated with executive function. Integration of structural and functional neuroimaging techniques is warranted to explore the neural mechanism of cognitive function in late-life depression. IC-P-021

COGNITIVE FUNCTION OF PATIENTS WITH PARTIAL ANTERIOR CIRCULATION INFARCT AND AMNESTIC MILD COGNITIVE IMPAIRMENT

Mei-Yan Zhang1,2, Qiong Yang3, Xin Yu1,2, Na Liu3, Dongsheng Fan3, Huali Wang1,2, 1Peking University Institute of Mental Health, Beijing, China; 2Key Laboratory for Mental Health, Ministry of Health, Beijing, China; 3Peking University Third Hospital, Beijing, China. Contact e-mail: [email protected] Background: Cerebral ischemia increases the risk of vascular cognitive impairment. The study aimed to compare the cognitive function of patients with partial anterior circulation infarct (PACI) and amnestic mild cognitive impairment (aMCI). Methods: Thirty patients meeting the classification criteria of PACI by Oxford Community Stroke Project (OCSP), 38 individuals with aMCI by Petersen criteria, and 63 healthy elderly controls were enrolled in this prospective study. Cognitive functions were assessed by Cognitive Ability Screening Instrument-C2.1 (CASI) within 1 month of diagnosis. The scores of nine cognitive domains included in CASI and the total score of CASI were used for group comparisons. Age, education and gender were entered as covariates in the general linear model for group comparisons. Results: Relative to control group (CASI ¼ 95.54 6 3.39), the total scores of CASI were significantly lower in PACI (CASI ¼ 86.90 6 11.88) and aMCI groups (CASI ¼ 89.87 6 5.82) (F(2) ¼ 16.835, P < 0.05). There was no significant difference in CASI total score between PACI and aMCI groups (P > 0.05). As illustrated in Figure 1, the scores of attention (P ¼ 0.000) and language (P ¼ 0.034) were markedly lower in PACI group when compared to NC group. Compared to aMCI group, the score of att6ention (P ¼ 0.000) was significantly lower in PACI group. Relative to control group, scores of short-term memory (P ¼ 0.000), abstract thinking and judgment (P ¼ 0.049), and category fluency (P ¼ 0.000) were lower in aMCI group. The score of category fluency was also lower in aMCI group than PACI group (P ¼ 0.020). Conclusions: Individuals with PACI present marked cognitive impairment, especially in attention and language. In comparison with aMCI individuals, PACI individuals may preserve executive function as measured with category fluency. The findings suggest the cognitive impairment due to cerebral ischemia may lie in different domains from that of neurodegenerative pathology. Further investigations in larger sample and on different subtypes of cerebral ischemia are warranted.