Alzheimer Disease: van der Flier W

Karas G, Sluimer J, Goekoop R, van der Flier W, Rombouts SA, Vrenken H, Scheltens P, Fox N, Barkhof F. · Department of Diagnostic Radiology, VU University Medical Center, Amsterdam, the Netherlands. · AJNR Am J Neuroradiol. · Pubmed #18296551 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is considered by many to be a prodromal phase of Alzheimer disease (AD). We used voxel-based morphometry (VBM) to find out whether structural differences on MR imaging could offer insight into the development of clinical AD in patients with amnestic MCI at 3-year follow-up. MATERIALS AND METHODS: Twenty-four amnestic patients with MCI were included. After 3 years, 46% had progressed to AD (n = 11; age, 72.7 +/- 4.8 years; women/men, 8/3). For 13 patients (age, 72.4 +/- 8.6 years; women/men, 10/3), the diagnosis remained MCI. Baseline MR imaging at 1.5T included a coronal heavily T1-weighted 3D gradient-echo sequence. Localized gray matter differences were assessed with VBM. RESULTS: The converters had less gray matter volume in medial (including the hippocampus) and lateral temporal lobe, parietal lobe, and lateral temporal lobe structures. After correction for age, sex, total gray matter volume, and neuropsychological evaluation, left-sided atrophy remained statistically significant. Specifically, converters had more left parietal atrophy (angular gyrus and inferior parietal lobule) and left lateral temporal lobe atrophy (superior and middle temporal gyrus) than stable patients with MCI. CONCLUSION: By studying 2 MCI populations, converters versus nonconverters, we found atrophy beyond the medial temporal lobe to be characteristic of patients with MCI who will progress to dementia. Atrophy of structures such as the left lateral temporal lobe and left parietal cortex may independently predict conversion.

Karas G, Scheltens P, Rombouts S, van Schijndel R, Klein M, Jones B, van der Flier W, Vrenken H, Barkhof F. · Department of Diagnostic Radiology, Vrije Universiteit Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. · Neuroradiology. · Pubmed #17955233 No free full text.

Abstract: INTRODUCTION: Alzheimer's disease (AD) usually first presents in elderly patients, but may also develop at an earlier age. Patients with an early age at onset tend to present with complaints other than memory impairment, such as visuospatial problems or apraxia, which may reflect a different distribution of cortical involvement. In this study we set out to investigate whether age at onset in patients with AD determines the pattern of atrophy on cerebral MRI scans. METHODS: We examined 55 patients with AD over a wide age range and analyzed their 3-D T1-weighted structural MRI scans in standard space using voxel-based morphometry (VBM). Regression analysis was performed to estimate loss of grey matter as a function of age, corrected for mini-mental state examination (MMSE) scores and sex. RESULTS: The VBM analyses identified multiple areas (including the temporal and parietal lobes), showing more atrophy with advancing age. By contrast, a younger age at onset was found to be associated with lower grey matter density in the precuneus. Regionalized volumetric analysis of this region confirmed the existence of disproportionate atrophy in the precuneus in patients with early-onset AD. Application of a multivariate model with precuneus grey matter density as input, showed that precuneal and hippocampal atrophy are independent from each other. Additionally, we found that a smaller precuneus is associated with impaired visuospatial functioning. CONCLUSION: Our findings support the notion that age at onset modulates the distribution of cortical involvement, and that disproportionate precuneus atrophy is more prominent in patients with a younger age of onset.

Ylikoski R, Jokinen H, Andersen P, Salonen O, Madureira S, Ferro J, Barkhof F, van der Flier W, Schmidt R, Fazekas F, Scheltens P, Waldemar G, Salvadori E, Pantoni L, Inzitari D, Erkinjuntti T, Anonymous00192. · Memory Research Unit, Department of Neurology, University of Helsinki, Helsinki, Finland. · Dement Geriatr Cogn Disord. · Pubmed #17565216 No free full text.

Abstract: BACKGROUND/AIMS: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) is a widely used rating instrument. The Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) includes additional tests reflecting mental speed and executive functions. The objective of this study was to compare the results of the two scales among subjects with various degrees of white matter hyperintensities (WMHs). METHODS: In the multicentre, multinational Leukoaraiosis and Disability in the Elderly (LADIS) study, 616 non-disabled subjects between the ages of 65 and 84 were examined using MRI, the ADAS-cog and VADAS-cog. The WMH rating from the MRI divided the patients into groups of mild (n = 280), moderate (n = 187) and severe (n = 149) degrees of change. RESULTS: Covariance analysis controlling for the effect of age and education revealed that the ADAS-cog differentiated only the mild and severe WMH groups, while the differences between all three groups were highly significant with the VADAS-cog. CONCLUSIONS: The VADAS-cog significantly differentiated between all the white matter groups. In comparison, the ADAS-cog differentiated only severe changes. Accordingly, the VADAS-cog may be a more sensitive endpoint in studies of patients with white matter load and vascular burden of the brain.