Methods

Patients referred for investigation of dementia were evaluated with a history, an examination, and a neuropsychological assessment and excluded if there was evidence of head trauma, a primary psychiatric diagnosis, stroke, hydrocephalus, or a metabolic, infectious, or endocrine cause of dementia. Patients fulfilling the criteria for frontotemporal dementia were excluded,7as were patients with pyramidal or extrapyramidal tract signs. Patients were excluded if T2 weighted MRI showed deep white matter hyperintensites. Nine healthy older adults (aged 66–80, mean 72 (SD 0.7) years, mini mental state examination (MMSE)8>28) were control subjects. Eleven patients (aged 49–80, mean 70 (SD 0.6) years, MMSE 6–21) who had a diagnosis of probable Alzheimer's disease, as defined by the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association (NINCDS)9 and dementia diagnosed from the diagnostic and statistical manual of mental disorders, 3rd ed, revised criteria for Alzheimer's disease,10 took part in the study. Patients with probable Alzheimer's disease and controls were re-examined at 3 to 6 month intervals by clinical examination and with the MMSE. Patients with probable Alzheimer's disease were only included if their MMSE declined over the period of observation of 1–2 years. DTI was performed with a 1.5 T GE scanner using a single shot, diffusion weighted spin echo EPI sequence. The full details of the acquisition indices have been previously published4 but briefly, we used 17 axial oblique slices, TR 10 seconds, TE 105 ms, FOV 30 cm, acquisition matrix 256×128, reconstructed to 256², 5 mm slice thickness, 1 mm gap per slice, four b values applied in six diffusion directions (B_max=875 s mm^-2). The total scanning time was 4 minutes 25 seconds. Brain tissue masks derived from coregistered T2 images (acquired with no diffusion gradients) were used to threshold pixels with anomalous signal from the LI images. Pixels were characterised as either anterior-posterior (green), left-right (red), or vertical (blue) depending on the direction of the eigenvector of the diffusion tensor.3Other colours indicated that the orientation of the fibres was not entirely in a single direction (fig 1). For intrasubject comparison of anisotropy, tracts were clustered into three groups on the basis of whether pixels were oriented within 45° of each of the three principal directions. Colour coding of the orientation of the fibres allowed ready identification of major WMTs, such as the splenium of the corpus callosum, superior longitudinal fasciculus, cingulum, and vertical fibres of the internal capsule by comparison with previously published data on DTI of white matter association pathways.11 For the splenium and cingulum, regions of interest (ROIs) encompassed the entire WMTs. For the vertical fibres of the internal capsule, only the blue colour coded pyramidal tracts were included within the ROI. For the superior longitudinal fasciculus, ROIs were placed in a posterior region of the WMTs encompassing green colour coded anterior-posterior association fibres. Differences between these regions for the two subject groups were analysed by analysis of variance (ANOVA) (table).

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Figure 1

Representative images from an aged matched control (left column) and a patient with probable Alzheimer's disease (right column). The MR images in the rows (top to bottom, respectively) are T2 weighted at the level of the internal capsule, corresponding LI anisotropy images, matching colour coded LI images, and colour coded LI images at the level of the superior longitudinal fasciculus. The splenium (red arrow), superior longitudinal fasciculus (light green arrow), cingulum (dark green), and pyramidal tract (light blue) are demonstrated in the colour coded LI maps.