[P‐137]: Acceleration of regional brain loss during progression of Alzheimer's disease

Background: Using the regional brain boundary shift integration technique (rBSI) and serial MRI, we recently demonstrated that rates of medial temporal lobe atrophy MTL-AR (%tissue lost/year) increase as normal subjects progress to MCI. The rise in MTL-AR precedes the onset of cognitive decline. At the time of diagnosis of AD, MTL-AR averages 2%, and it increases by 0.5% for each subsequent year after the diagnosis. In normal elderly, MTL-AR averaged 0.3% and did not depend on age. It is unknown if the acceleration of brain tissue loss continues in more advanced AD. Objectives: (1) To assess the distribution of MTL-AR in advanced stages of AD, (2) to extend the measurements to a comprehensive set of anatomically defined brain lobes. Methods: Sixteen AD patients (age 74.9 /-6.5 years, 50% women, 14.9 /-2.4 yrs education) received clinical, neuropychological and MRI examinations at baseline and after 2 years. MMSE scores were 22.3 /-3.3 at baseline and 18.5 /-7.1 at followup. Intracranial cavity was partitioned into frontal, parietal, lateral temporal, medial temporal, and occipital lobes, plus three additional regions encompassing sensori-motor, cingulate, and insular cortices. For each region we computed the baseline and the follow-up atrophy A and the annual rate of atrophy AR. ANOVA and post hoc Tukey’s range test was used to identify homogenous sets of brain regions at alpha 0.05. Results and Conclusions: AR were heterogeneously distributed across regions (ANOVA, F 11.1, p 0.001), with the highest values in lateral temporal (4.4 /-3.5, mean /-standard deviation in %/year), MTL (4.1 /-2.4), and insular (3.4 /-1.8) regions; intermediate values in the parietal (1.6 /-1.2) and cingulate (1.6 /-1.0) regions; and the lowest levels in occipital, sensorimotor and frontal regions. In the MTL but in no other region there was a very strong association between baseline A and AR (see graph, p 0.0003, R 0.78), i.e. the patients with more pronounced baseline MTL atrophy show larger annual rates of brain loss. Thus, even in an advanced stage of AD, there is a preferential vulnerability of the medial temporal, lateral temporal and insular brain regions and a continuing territorial spread of the disease process, reaching a dramatic level of 10%/year in the most severe cases. SUNDAY, JUNE 19, 2005 IMPACT ON POLICY, ETHICS AND CARE P-138—P-149