Association of Preoperative Posterior Cingulate Cortex Microstructural Damage With Postoperative Delirium.
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2026-06
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Postoperative delirium is the most common postsurgical complication in older adults and is associated with an increased risk of long-term cognitive decline and Alzheimer's disease (AD) and related dementias (ADRD). However, the neurological basis of this increased risk-whether postoperative delirium unmasks latent preoperative pathology or leads to AD-relevant pathology after perioperative brain injury-remains unclear.Methods
To investigate potential brain microstructural abnormalities associated with postoperative delirium and cognitive function, we analyzed pre- and post-operative Neurite Orientation Dispersion and Density Imaging (NODDI) MRI data within the posterior cingulate cortex (PCC) from 110 patients aged ≥60 years who underwent non-cardiac/non-intracranial surgery.Results
We found increased free water (FISO) and decreased neurite density index (NDI) and orientation dispersion index (ODI) in the dorsal PCC before surgery among those who later developed postoperative delirium (n = 12) versus those who did not (n = 98). Preoperative dorsal PCC NDI and ODI values were also positively associated with preoperative attention/concentration performance, independent of age, education level, and global brain atrophy (NDI: = 0.29 (95% CI, 0.10-0.50), P = .008; ODI: = 0.29 (95% CI, 0.03-0.44), P = .004). Yet, these diffusion metrics were not correlated with cerebrospinal fluid amyloid beta (Aβ) positivity or levels.Conclusions
These results suggest that preoperative latent brain abnormalities within the dorsal PCC may underlie attention/concentration deficits and susceptibility to postoperative delirium, yet these dorsal PCC NODDI abnormalities were not significantly associated with CSF Aβ levels (a measure of brain Amyloid deposition). Our findings highlight microstructural vulnerability within the PCC, a key region of the default mode network, as a neuroanatomic locus that can help explain the link between preoperative attention/concentration deficits and increased postoperative delirium risk among vulnerable older surgical patients.Type
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Reekes, Tyler H, Vinith R Upadhya, Jenna L Merenstein, Mary Cooter Wright, Mary Cooter Wright, David J Madden, Melody A Reese, Piper C Boykin, et al. (2026). Association of Preoperative Posterior Cingulate Cortex Microstructural Damage With Postoperative Delirium. Anesthesia and analgesia. 10.1213/ane.0000000000008127 Retrieved from https://hdl.handle.net/10161/35441.
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Scholars@Duke
David Joseph Madden
My research focuses primarily on the cognitive neuroscience of aging: the investigation of age-related changes in perception, attention, and memory, using both behavioral measures and neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI).
The behavioral measures have focused on reaction time, with the goal of distinguishing age-related changes in specific cognitive abilities from more general effects arising from a slowing in elementary perceptual processes. The cognitive abilities of interest include selective attention as measured in visual search tasks, semantic and episodic memory retrieval, and executive control processes.
The behavioral measures are necessary to define the cognitive abilities of interest, and the neuroimaging techniques help define the functional neuroanatomy of those abilities. The PET and fMRI measures provide information regarding neural activity during cognitive performance. DTI is a recently developed technique that images the structural integrity of white matter. The white matter tracts of the brain provide critical pathways linking the gray matter regions, and thus this work will complement the studies using PET and fMRI that focus on gray matter activation.
A current focus of the research program is the functional connectivity among regions, not only during cognitive task performance but also during rest. These latter measures, referred to as intrinsic functional connectivity, are beginning to show promise as an index of overall brain functional efficiency, which can be assessed without the implementation of a specific cognitive task. From DTI, information can be obtained regarding how anatomical connectivity constrains intrinsic functional connectivity. It will be important to determine the relative influence of white matter pathway integrity, intrinsic functional connectivity, and task-related functional connectivity, as mediators of age-related differences in behavioral measures of cognitive performance.
Ultimately, the research program can help link age-related changes in cognitive performance to changes in the structure and function of specific neural systems. The results also have implications for clinical translation, in terms of the identification of neural biomarkers for the diagnosis of neural pathology and targeting rehabilitation procedures.
Joseph P. Mathew
Current research interests include:
1. The relationship between white matter patency, functional connectivity (fMRI) and neurocognitive function following cardiac surgery.
2. The relationship between global and regional cortical beta-amyloid deposition and postoperative cognitive decline.
3. The effect of lidocaine infusion upon neurocognitive function following cardiac surgery.
4. The association between genotype and outcome after cardiac surgery.
5. Atrial fibrillation following cardiopulmonary bypass.
Michael Devinney
My work uses translational neuroscience approaches, such as cerebrospinal fluid molecular assays, sleep EEG, cognitive testing, and delirium assessment to identify mechanisms of delirium. Delirium is a syndrome of disrupted attention and consciousness that occurs in ~20% of the >19 million older surgery patients and ~50% of the >5 million intensive care unit (ICU) patients in the United States every year. Delirium is also associated with increased risk for Alzheimer’s disease and related dementias (ADRD), yet there are no FDA-approved drugs to prevent it, due to a major gap in our understanding of its underlying mechanisms. Our current work aims to discover potential mechanisms of delirium that could be targeted in future studies. We have recently found that increased blood-brain barrier dysfunction is associated with postoperative delirium, but it is unknown what inflammatory mediators actually cross the disrupted blood-brain barrier to drive delirium. Using mass spectrometry proteomics, we are examining the relationship of proteins and inflammatory markers found in the cerebrospinal fluid 24-hours following surgery with postoperative delirium. We are also interested in strategies that potentially protect the blood-brain barrier following surgery. Since sleep disruptions can cause blood-brain barrier dysfunction, we are conducting a study to determine the efficacy of suvorexant to improve postoperative sleep and reduce delirium severity in older surgical patients. Finally, we are working to extend these investigations to ICU patients, who are often more severely affected by delirium and more frequently develop long-term sequelae such as post-ICU long-term cognitive impairment (that is similar in magnitude to Alzheimer’s disease and related dementias).
Jeffrey Nicholas Browndyke
Dr. Browndyke is an Associate Professor of Behavioral Health & Neurosciences in the Department of Psychiatry & Behavioral Sciences. He has a secondary appointment as Assistant Professor of Cardiovascular & Thoracic Surgery.
Dr. Browndyke's research interests involve the use of advanced neurocognitive and neuroimaging techniques for perioperative contributions to delirium and later dementia risk, monitoring of late-life neuropathological disease progression, and intervention/treatment outcomes. His research also involves novel telehealth methods for remote neurocognitive evaluation and implementation of non-invasive neuromodulatory techniques to assist in postoperative recovery and dementia risk reduction.
Dr. Browndyke's clinical expertise is focused upon geriatric neuropsychology with an emphasis in the assessment, diagnosis, and treatment of dementia and related disorders in adults and US veteran patient populations.
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