Abstract
The cognitive health of surgical patients over the age of 60 is of increasing concern to the providers, patients, and their families. Many elderly patients present with cognitive impairment that is not always detected in a busy surgical practice. Many patients may experience an apparent acceleration of decline afterward in the postoperative period. Here we present a typical case and then review appropriate pre-, intra-, and postoperative management of such patients in the context of the disease pathophysiology. We then discuss the evidence for an acceleration of this neuropathology and what should be disclosed in the informed consent discussion.
Keywords
Alzheimer’s disease, amyloid beta, tau, neurodegeneration, dementia, mild cognitive impairment, CSF biomarkers
Case Synopsis
A 78-year-old woman, living independently at home, falls and sustains a hip fracture. She is admitted to the hospital, and the medical history reveals only hypertension, for which she takes hydrochlorothiazide. Cleared for surgery, she undergoes a 3-hour hip arthroplasty under general endotracheal anesthesia with isoflurane with no complications. She experiences moderate blood loss (900 mL) but no episodes of hypotension or hypoxemia. After extubation, she is noted to be delirious in the postanesthesia care unit. Her delirium waxes and wanes over the next 24 to 36 hours, and she is discharged to a rehabilitation facility on postoperative day 5. Her course in rehab is difficult, with the staff noting depression, forgetfulness, and inattention. Her family describes her as being “very different” from before her fall, although they do admit, in retrospect, that she had been getting a “little forgetful.” She is discharged to home, where it becomes apparent that she cannot perform the activities of daily living, and she is transferred to an assisted care facility. After 6 months, with no improvement, and a formal evaluation by a geriatric neurologist, including a lumbar puncture for cerebrospinal fluid (CSF) biomarkers, she is diagnosed with dementia of the Alzheimer type.
Problem Analysis
Recognition
Older patients present for surgery with a number of preexisting comorbidities, and among the most common are the age-related neurodegenerative disorders. There are a large number of these disorders, often with overlapping neuropathology and symptomatology, but Alzheimer’s disease (AD) is the most prevalent. It is estimated that 10% of Americans over 65 years of age have AD, and 30% of those over 85 have the disorder. The neuropathology responsible for the disease is thought to start more than 20 years before diagnosis. For example, in the earliest stages, the protein amyloid beta begins to aggregate extracellularly in specific areas of the brain. This can occur slowly over years and is thought to gradually deplete the levels circulating in the CSF—forming the basis of one of the primary diagnostic tests for AD. At some stage the amyloidopathy begins to promote tau detachment from microtubules and its aggregation into intracellular filaments called neurofibrillary tangles. This latter process appears to be more cytotoxic than the amyloidopathy and is associated with both enhanced neuroinflammation and cell loss (neurodegeneration). The excess tau, perhaps released from dying neurons, ends up in the CSF forming the other feature of the CSF diagnostic test. Only at this later stage, when there is clear tauopathy and significant cell loss, apparent on magnetic resonance scans as thinning cortical and hippocampal gray matter layers, do changes in cognitive ability become noticeable.
Cognitive changes are noted initially in memory and executive function, but extend to other domains as well as sensory function as the neurodegeneration progresses. Clinically, AD is divided into two primary stages: mild cognitive impairment (MCI) (termed mild neurocognitive disorder in DSM-5) and Alzheimer’s disease (AD) or dementia (termed major neurocognitive disorder in DSM-5). Each of these stages is being further divided based largely on recent advances in biomarkers. Diagnosis and staging is currently based on three primary modalities: neuropsychological testing, CSF biomarkers, and amyloid positron emission tomography (PET). Newer forms of imaging (e.g., tau) and perhaps blood-based biomarkers will add significantly to the diagnosis and staging in the near future.
This scenario represents the progression of the “late-onset” or sporadic form of AD, but a much rarer form is observed in people 30 to 50 years of age, almost always due to specific mutations in elements of the amyloid pathway. There exist other genetic risk factors for early acceleration of the sporadic form of AD, most notably the ApoEε4 allele.
The neurodegenerative disorders present two primary sets of concerns in the perioperative setting. The first regards the changes in management required for the patient with neurodegeneration, and the second regards the impact of the perioperative period on the trajectory of disease neuropathology.
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