P2-198 Effects of age, cerebrovascular disease and APOE ε4 on entorhinal and hippocampal atrophy rates

Poster Session P2: Diagnosis and Disease Progression - Neuroimaging and cerebellum. Results: Individuals with MCI showed smaller whole brain volumes and temporal lobes, relative to healthy controls. Conclusions: Brain abnormalities are present in individuals with MCI before the clinical onset of AD.

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P E R F U S I O N M R / S T U D Y O F DEMENTIA:

PRELIMINARY RESULTS

H. Michael Gach*, Weiying Dai, Venkata Lakkavaram, Stephen Z. Grahovac, James T. Becker, Steven T. DeKosky, Lewis H. Kuller, Oscar L. Lopez. University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail:

• AND APOE e4 ON ENTORHINAL AND

g ach @pitt.edu

HIPPOCAMPAL ATROPHY RATES

accurate identification of Alzheimer's disease (AD) predictors, and effective therapies. The University of Pittsburgh is conducting a study to identify predictors associated with AD and its precursor, mild cognitive impairment (MCI), using magnetic resonance imaging (MRI) at 1.5 T. Objective(s): The objective of the MRI study is to identify changes in cerebral structure and hemodynamics associated with the progression of dementia. Methods: Elderly volunteers (normal, MCIs, and early AD), recruited from the cardiovascular health study (CHS), received neuropsychological exams, and baseline and follow-up MRIs. The 1 hour MRI exams included highresolution strnctural imaging, noninvasive peffusion MRI using continuous arterial spin labeling (CASL) with double adiabatic inversion (DAI) control, saturation recovery T1 maps, and phase contrast velocimetry. Images were analyzed oft±he using Statistical Parametric Mapping (SPM) for gray/white matter segmentation, registration, and motion correction. Absolute perfusion rates were calculated using CASL kinetic models that incorporate experimental differences between subjects. Results: Gray matter perfusion and internal carotid (IC) velocities appear to be elevated in MCIs relative to normal and AD subjects (Table 1). T1 in the presence of (Tlobs) was slightly lower in MCIs. However, these findings are not yet statistically significant due to the low number of subjects analyzed to date. These results are also subject to change as the accuracy of the hemodynamic models used to convert the raw data into perfusion rates are improved and more studies are analyzed. In addition, the incidence of cerebrovascular disease and patient motion during the exam was found to rise with the diagnosis of dementia. Conclusions: A recent postmortem study of MCI found increased choline acetyltransferase (CHAT) in MCIs compared to normals and early dementia. Elevated perfusion in MCIs, if verified, may suggest the existence of a compensatory mechanism involving ChAT that exists in MCIs but ceases as the disease reaches early AD. Therapy that successfully targets this mechanism may delay the onset of AD. The correlation of cerebrovascular disease with dementia in our study is consistent with other studies.

E F F E C T S O F AGE, CEREBROVASCULAR DISEASE

Background: The prevention and treatment of dementia requires rapid and

Antao Du* 1, Norbert Schuff t , Linda L. Chao I , William J. Jagust 2, Joel H. Kramer 3, Bruce L. Miller 3 , Bruce R. Reed z, David Norman 3, Helena C. Chui 4, Michael W. Weiner 1. 1VA Medical Center, San Francisco, San

Francisco, CA, USA; 2University of California, Davis, Davis, CA, USA; 3University of California, San Francisco, San Francisco, CA, USA; 4University of Southern California, Los Angeles, CA, USA. Contact e-mail: antao @itsa. ucsf eda Background: MRI measured volume changes of entorhinal cortex (ERC) and hippocampus over time may be useful in predicting AD before clinical symptoms develop and in assessing treatment effects. However, significant rates of ERC and hippocampal atrophy are also observed in cognitive normal (CN) elderly, although magnitudes are substantially smaller than in AD. In addition, subcortical lacunes, white matter hyperintensities (WMH) and apolipoprotein E s4 allele (AOPE s4) may affect the atrophy rates of ERC and hippocalnpus in CN elderly. Objective: To explore the extent to which age, presence of subcortical lacunes, W M H and APOE s4 are associated with increased atrophy rates of entorhinal cortex (ERC) and hippocampus in normal aging. Methods: Longitudinal MRI studies were performed on 53 CN elderly with an average interscan period of 3.4 4- 1.0 years. CN subjects remained cognitively normal within the duration of the study. Cerebral vascular disease was assessed by quantifying the number of subcortical lacunes and the extent of WMH. ERC and hippocampal volumes were measured on volumetric Tl-weighted images.17 subjects had subcortical lacunes. 13 subjects had at least one APOE e4 allele. A multivariate linear regression model was used to test for effects of age, presence of subcortical lacunes, extent of WMH and APOE e4 on atrophy rates of ERC and hippocampus. Results: In absence of subcortical lacunes, atrophy rates of both ERC (F1,34 = 5.8, p < 0.05) and hippocampus (F1,34 = 10.6, p < 0.01) increased with increasing age, independent of W M H volume and APOE e4 status. When CN subjects with subcortical lacunes were included, both increasing age (both p < 0.03) and presence of subcortical lacunes (both p < 0.02), but not W M H volume and APOE e4 status, explained increased atrophy rates of ERC and hippocampus. Estimations from linear regressions indicated that presence of subcortical lacunes increases atrophy rates from 0.8 :t= 0.7%/year to 1.7 4- 1.3%/year for ERC and from 0.9 :t: 0.9%/year to 2.0 :t= 1.3%/year for hippocampus in normal aging. Conclusion: Age and presence of subcortical lacunes, but not W M H and APOE e4 status, were associated with higher rates of ERC and hippocampus. Therefore, age and presence of subcortical lacunes should be considered when using longitudinal MRI data to predict development of AD and assess treatment effect.

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PATTERNS OF BRAIN ATROPHY IN EARLY-ONSET VERSUS LATE-ONSET ALZHEIMER'S DISEASE: RELEVANCE OF POSTERIOR CINGULATE ATROPHY

Giorgos Karas, Philip Scheltens, Serge Rombouts, Ronald van Schijndel, Frederik Barkhof*. VUMC, Amsterdam, Netherlands. Contact e-mail:

[email protected] Background: Early-onset Alzheimer's disease is characterized by greater synaptic loss and a more severe clinical picture. Objective(s): to differentiate atrophy patterns in early-onset (EAD) and late-onset (LAD) Alzheimer's disease (AD). Methods: Structural MRI scans (heavily T1weighted MPRAGE) from 20 patients diagnosed with EAD (onset of symptoms before the age of 65 years) and from 37 LAD patients were collected. Scans were visually inspected for quality and movement artifacts. Age of the patients (SD) were: LAD: 72.8 (12.7), EAD: 59.2 (4.4). The scans were analyzed with voxel-based morphometry as has been described

Abstract P2-199 Table 1. Preliminary results from 1.5 T MRI hemodynamic studies Subject Classification}

Normals (N = 20) MCI (N = 18) Early Dementia (N = 11)

Tlobs (ms)

Velocity (cm/s)

Gray Matter

White Matter

IC Left

IC Right

1061 ± 15 1050 4- 16 1078 ± 30

801 ± 10 784 ± 8 801 ± 10

19.5 ± 1.3 21.0 ± 0.9 18.4 t 1.1

19.0 ± 0.9 20.6 ± 1.1 20.9 ± 2.2

Perfusion (ml/lOOg-min) Gray Matter Hemispheres

White Matter Hemispheres

Left

Right

Left

Right

46.8 ± 5.9 55.1 ± 4.9 47.9 ± 6.4

43.6 :t: 5.7 51.3 4- 4.9 43.6 ± 5.8

17.0 ± 1.9 19.7 ± 1.9 16.7 ± 2.3

16.2 4- 1.9 19.2 ± 1.6 17.4 ± 2.6