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Using time\u2010shift analysis of blood\u2010oxygenation\u2010level\u2010dependent (BOLD) signals, we explored associations between cerebral blood transit time, amyloid beta (A\u03b2) pathology, and cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We included 131 non\u2010demented individuals from the Alzheimer's Disease Neuroimaging Initiative. Three transit metrics \u2013 termed Lag\n                      <jats:sub>ICA\u2010SSS<\/jats:sub>\n                      , Lag\n                      <jats:sub>ICA\u2010global<\/jats:sub>\n                      , and Lag\n                      <jats:sub>global\u2010SSS<\/jats:sub>\n                      \u2013 were derived from BOLD time lags between the internal carotid artery (ICA), superior sagittal sinus (SSS), and global signal. Associations between transit metrics, A\u03b2 burden, and cognition were investigated through cross\u2010sectional and longitudinal analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      At baseline, prolonged Lag\n                      <jats:sub>ICA\u2010global<\/jats:sub>\n                      and Lag\n                      <jats:sub>ICA\u2010SSS<\/jats:sub>\n                      were associated with higher A\u03b2 burden, while their adverse effect on cognition was largely mediated by A\u03b2 pathology. In longitudinal analyses, prolonged Lag\n                      <jats:sub>global\u2010SSS<\/jats:sub>\n                      and Lag\n                      <jats:sub>ICA\u2010SSS<\/jats:sub>\n                      predicted faster A\u03b2 accumulation. Synergistic interactions between Lag\n                      <jats:sub>ICA\u2010global<\/jats:sub>\n                      , Lag\n                      <jats:sub>global\u2010SSS<\/jats:sub>\n                      , and A\u03b2 burden were linked to accelerated cognitive decline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Prolonged blood transit time can reflect early vascular impairment in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Vascular risks are associated with prolonged arterial transit time (Lag\n                            <jats:sub>ICA\u2010global<\/jats:sub>\n                            ) and cerebral blood transit time (Lag\n                            <jats:sub>ICA\u2010SSS<\/jats:sub>\n                            ).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Prolonged venous blood transit time (Lag\n                            <jats:sub>global\u2010SSS<\/jats:sub>\n                            ) and Lag\n                            <jats:sub>ICA\u2010SSS<\/jats:sub>\n                            are linked to accelerated A\u03b2 accumulation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            A\u03b2 burden mediates the association between prolonged Lag\n                            <jats:sub>ICA\u2010global<\/jats:sub>\n                            and Lag\n                            <jats:sub>ICA\u2010SSS<\/jats:sub>\n                            and cognitive impairment.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            A\u03b2 Amyloid burden may interact synergistically with prolonged Lag\n                            <jats:sub>ICA\u2010global<\/jats:sub>\n                            and Lag\n                            <jats:sub>global\u2010SSS<\/jats:sub>\n                            to exacerbate cognitive decline.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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