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 (χ² = 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; p55 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.

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