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For WBHA, BET was performed using structural MRI and three different BET software programs, namely High-Definition-BET (HD-BET), FMRIB Software Library (FSL), and Statistical Parametric Mapping (SPM). Skewness and mode-to-mean ratio (MMR) were measured using brain-extracted PET. The Top 20% Map was generated from SPM BET images, separated into gray and white matter voxels, and their ratio was calculated as the GW-ratio. The CL value was computed using structural MRI. A\u03b2-negativity or positivity was visually determined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Skewness from three BET methods was strongly negatively correlated with CL. Skewness (HD-BET) showed the strongest correlation (R\u2009=\u2009-0.9043). Moreover, the GW-ratio strongly correlated with CL (R\u2009=\u20090.8332), whereas MMR, particularly MMR (FSL) (R\u2009=\u20090.2112), showed poor correlation. All indicators significantly distinguished A\u03b2-negative from A\u03b2-positive visuals. CL had the highest area under the curve (AUC, 0.9959), followed by skewness (HD-BET) (0.9927), Top 20% GW-ratio (0.9872), and skewness (SPM) (0.9779), with no statistical difference between CL and skewness (HD-BET) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.5763). Based on mean and SD values from 118 cognitively unimpaired (G-CDR\u2009=\u20090, MMSE\u2009\u2265\u200928) and visually A\u03b2-negative participants, 95% cut-off limits for A\u03b2-negative individuals without dementia symptoms were: CL\u2009\u2264\u200912.9, skewness (HD-BET)\u2009\u2265\u20090.1769, MMR (HD-BET)\u2009\u2264\u20090.9372, skewness (FSL)\u2009\u2265\u20090.1819, MMR (FSL)\u2009\u2264\u20091.9132, skewness (SPM)\u2009\u2265\u2009-0.0382, MMR (SPM)\u2009\u2264\u20091.1274, and GW-ratio\u2009\u2264\u20090.1079.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WBHA using MRI-based BET and GW-ratio showed strong correlations with CL and demonstrated a diagnostic performance comparable to that of CL.<\/jats:p>\n                  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Atsushi Shima was supported by a collaborative research project with Sumitomo Pharma Co., Ltd. from April 2024 to January 2025, and has been supported by RACTHERA Co., Ltd. since February 2025. All other authors declare no conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Data supporting the findings of this study are available from the corresponding author [R.Y.] upon reasonable request.","order":2,"name":"Ethics","label":"Data Avilability","group":{"name":"EthicsHeading","label":"Declarations"}}]}}