Vascular risk factors are associated with a decline in resting-state functional connectivity in cognitively unimpaired individuals at risk for Alzheimer's disease
Theresa Köbe,
Alexa Pichet Binette,
Jacob W. Vogel,
Pierre-François Meyer,
John C.S. Breitner,
Judes Poirier,
Sylvia Villeneuve
Affiliations
Theresa Köbe
Department of Psychiatry, McGill University, H3A 1A1, Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StoP-AD) Centre, H4H 1R3, Montreal, Quebec, Canada; German Center for Neurodegenerative Diseases (DZNE), 01307, Dresden, Germany; Corresponding author.
Alexa Pichet Binette
Department of Psychiatry, McGill University, H3A 1A1, Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StoP-AD) Centre, H4H 1R3, Montreal, Quebec, Canada
Jacob W. Vogel
Montreal Neurological Institute, McGill University, H3A 2B4, Montreal, QC, Canada
Pierre-François Meyer
Department of Psychiatry, McGill University, H3A 1A1, Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StoP-AD) Centre, H4H 1R3, Montreal, Quebec, Canada
John C.S. Breitner
Department of Psychiatry, McGill University, H3A 1A1, Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StoP-AD) Centre, H4H 1R3, Montreal, Quebec, Canada
Judes Poirier
Department of Psychiatry, McGill University, H3A 1A1, Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StoP-AD) Centre, H4H 1R3, Montreal, Quebec, Canada
Sylvia Villeneuve
Department of Psychiatry, McGill University, H3A 1A1, Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StoP-AD) Centre, H4H 1R3, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, H3A 2B4, Montreal, Quebec, Canada; Corresponding author at: Department of Psychiatry, McGill University, Faculty of Medicine, Douglas Mental Health University Institute, Perry Pavilion, Room E3417.1, 6875 LaSalle Blvd, Montreal, QC H4H 1R3, Canada
Resting-state functional connectivity is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. However, evidence is lacking regarding longitudinal changes in functional connectivity. This study includes 247 cognitively unimpaired individuals with a family history of sporadic AD (185 women/ 62 men; mean [SD] age of 63 [5.3] years). Plasma total-, HDL-, and LDL-cholesterol and systolic and diastolic blood pressure were measured at baseline. Global (whole-brain) brain functional connectivity and connectivity from canonical functional networks were computed from resting-state functional MRI obtained at baseline and ~3.5 years of annual follow-ups, using a predefined functional parcellation. A subsample underwent Aβ- and tau-PET (n=91). Linear mixed-effects models demonstrated that global functional connectivity increased over time across the entire sample. In contrast, higher total-cholesterol and LDL-cholesterol levels were associated with greater reduction of functional connectivity in the default-mode network over time. In addition, higher diastolic blood pressure was associated with global functional connectivity reduction. The associations were similar when the analyses were repeated using two other functional brain parcellations. Aβ and tau deposition in the brain were not associated with changes in functional connectivity over time in the subsample. These findings provide evidence that vascular burden is associated with a decrease in functional connectivity over time in older adults with elevated risk for AD. Future studies are needed to determine if the impact of vascular risk factors on functional brain changes precede the impact of AD pathology on functional brain changes.
