Single photon emission computed tomography (SPECT) studies have been applied for evaluation of regional cerebral blood flow (rCBF) in various neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and ALS with dementia (ALS-D). Brain perfusion SPECT using statistical image analysis is useful for accurate and objective diagnosis to evaluate slight decreases in rCBF, even in cases difficult to assess by visual inspection. We have used statistical parametric mapping (SPM), three-dimensional stereotactic surface projection (3D-SSP), easy Z-score imaging system (eZIS) as statistical image analyses. ALS-D cases, even if a case manifests minimal mentality change, showed obvious rCBF reduction in the bilateral prefrontal area with some irregularity and laterality of its decrease. This abnormality was clear in ALS-D compared with classic ALS. Our study has demonstrated that brain perfusion SPECT imaging using statistical image analyses is quite useful as an adjunct to presume the existence of dementia in ALS, even if ALS patients have trouble in verbal or manual communication of the language because of progressive bulbar symptoms and muscle weakness. Thus, for ALS patients with any subtle signs and symptoms suggesting dementia, we recommend a SPECT study with use of statistical image analyses.