How might increasing focus on functional brain networks lead to more effective dementia therapies? The first hope relates to patient categorization, and AD provides an illustrative example. Among healthy older persons without cognitive impairment, high levels of brain Aβ are suspected to represent preclinical AD.141 Pinpointing presymptomatic, Aβ-associated network disruption, as reported in several recent studies,142,143 might identify a subgroup most likely to benefit from a disease-modifying pharmacological treatment. Similarly, network analysis may provide sensitive markers of preclinical FTD (e.g., in gene mutation carriers) and help to distinguish patients on the PD-DLB spectrum. Other approaches may seek to recalibrate networks directly. Phase I trials of deep brain and transcranial magnetic stimulation targeting cognitive circuits have shown improvement of network-wide metabolic function or cognitive function in patients with AD.144,145 Finally, task-free fMRI and neurophysiological methods provide attractive candidates for longitudinal, disease-monitoring biomarkers due to the safe and repeatable nature of these techniques. Whether these methods will prove successful in detecting and monitoring clinical change is a question that awaits future studies. In light of cross-sectional correlations between network connectivity strength and clinical severity,58,59 cautious optimism seems justified.
