Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by insidious and progressive impairment of cognition, emotion, and memory. Though pain in patients with AD is a major medical concern it is under diagnosed and under treated in patients, compared to cognitively healthy elderly. Further complicating matters, subjective self-report of pain by becomes increasingly compromised with disease progression; this often leaves clinicians and caregivers no choice but to rely on discerning pain from behavior alone. Patients also report pain at a lower frequency and intensity than healthy seniors (HS). These findings, coupled with recognition that AD pathology affects many pain processing brain regions, have prompted examination of whether AD alters pain perception. While there is evidence that AD actually predisposes heightened perception of pain, several issues remain: experimental work is limited to a handful of studies, whose results have been inconsistent; few examinations of pain in AD have included patients with advanced disease; the neural mechanism underlying altered pain in AD is not clear. I addressed these gaps in the literature by examining subjective, behavioral, and autonomic pain responses in 33 HS and 38 patients with varying severities of AD. A subset of these subjects (24 HS and 20 AD) were scanned, using fMRI. I then determined how the functional connectivity of various resting-state networks (RSNs) were associated with measured pain responses. I found that AD patients rated low-level stimuli as more painful than HS. Also, patients, regardless of severity, showed greater degrees of pain behaviors than HS - both with respect to global behaviors as measured by a clinical pain scale and facial responses as measured by an experimental tool. In contrast, autonomic responses were blunted with advancing AD. Altered pain responses in AD were associated with altered function of RSNs involved in attention and internal mentation, affect, somatosensation, and interoception (p<0.05, FWE corrected). These findings provide further evidence and an improved understanding of the neural basis for heightened pain sensitivity in patients with AD. They also emphasize the necessity to improve pain assessment and treatment strategies for a vulnerable patient population set to expand greatly in the coming decades.
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