Anterior-medial thalamic lesions in dementia: frequent, and volume dependently associated with sudden cognitive decline.

BACKGROUND The anterior-medial thalamus (AMT), which is associated with memory processing, is severely affected by Alzheimer's disease pathology and, when damaged, can be the sole cause of dementia. OBJECTIVE To assess the frequency of magnetic resonance imaging (MRI) hyperintensities affecting the AMT, and their relationship with sudden cognitive decline. METHODS 205 consecutive participants from a university cognitive neurology clinic underwent clinical evaluation, neuropsychological testing and quantitative MRI. RESULTS AMT hyperintensities >5 mm3 occurred in 0 of 34 normal controls but were found in 5 of 30 (17%) participants with cognitive impairment with no dementia (CIND), 9 of 109 (8%) patients with probable Alzheimer's disease, 7 of 17 (41%) with mixed disease and 8 of 15 (53%) with probable vascular dementia (VaD). AMT hyperintensities occurred more often in participants with stepwise decline than in those with slow progression (chi2 = 31.7; p<0.001). Of the 29 people with AMT hyperintensities, those with slow progression had smaller medial temporal width (p<0.001) and smaller anterior-medial thalamic hyperintensities (p<0.001). In a logistic regression model, both variables were significant, and the pattern of decline was correctly classified in 86% of the sample (Cox and Snell R2 = 0.56; p<0.001). Those with AMT hyperintensities >55 mm3 were likely to have stepwise decline in cognitive function regardless of medial temporal lobe width; in contrast, those with smaller AMT hyperintensities showed a stepwise decline only in the absence of medial temporal lobe atrophy. All patients with VaD had left-sided AMT hyperintensities, whereas those with CIND had right-sided AMT hyperintensities. CONCLUSIONS AMT hyperintensities >55 mm3 probably result in symptomatic decline, whereas smaller lesions may go unrecognised by clinicians and radiologists. Only half of those with AMT hyperintensities had diagnoses of VaD or mixed disease; the other AMT hyperintensities occurred in patients diagnosed with Alzheimer's disease or CIND. These silent hyperintensities may nevertheless contribute to cognitive dysfunction. AMT hyperintensities may represent a major and under-recognised contributor to cognitive impairment.