Plasma markers of Alzheimer’s Disease and changes in postoperative cognition
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Dementia is a major public health problem with direct consequences to the individual, family, society, and the healthcare system. The pathophysiology of Alzheimer's disease and related dementias (ADRD) is incompletely understood despite its prevalence. The pathology of ADRD begins years before clinical symptoms emerge, therefore the need to provide early diagnosis in order to develop follow up and potential therapy is urgently needed before the neurodegenerative process advances to a later stage. The central hypothesis of this supplement is that patients with seemingly intact cognition, but with positive plasma AD biomarkers are vulnerable to the stress of major surgery and anesthesia, resulting in a higher likelihood of developing postoperative delirium, subsyndromal delirium, and acute cognitive decline. Therefore, perioperative period provides an earlier window to diagnosing cognitive impairment including AD before clinically significant symptoms are recognized, thus providing an earlier path to follow-up and intervention to potentially slow the rate of cognitive decline. The surgical setting provides a unique natural environment to study how the vulnerable brain may respond in the setting of perioperative stress such as pain, exposure to new medications, or sleep disruption. Routine preoperative evaluation does not formally assess for early signs of memory impairment because most individuals with AD and their families don't seek evaluation for cognitive impairment until it affects their daily functioning, which occurs later in the pathophysiology of AD. Recent research has shown that plasma AD biomarkers, including Aβ42/40 and p-tau181, are highly correlated with brain amyloid and tau burden detected by neuropathological assessment and amyloid and tau neuroimaging. Plasma AD biomarkers have high sensitivity in predicting AD, therefore can provide a relatively non-invasive benchmark for AD detection, even in asymptomatic or prodromal phases. This supplement will leverage cognitive, surgical, clinical, and tissue banking from over 672 patients aged 65 years or older undergoing major elective surgery, a cohort selected from the parent grant. Cognitive tests were conducted before and daily in the first 2-3 days after surgery; incident delirium was assessed each day after surgery; and functional status (activities of daily living, instrumental activities of daily living) was assessed at 1 month after surgery. We hypothesize that patients with postoperative delirium/subsyndromal delirium are more likely to have positive plasma AD biomarkers, and those with preoperative plasma biomarkers of AD are more likely to decline in cognitive functioning and daily functioning in the days after surgery through 1 month after surgery. Our study will not only inform the pathophysiology of delirium, but will also provide an earlier window to diagnosing patients at risk for developing AD in order to guide interventions that may slow the rate of longer-term cognitive and functional decline.
