Person:

Hshieh, Tammy

Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. This review examines current understanding of the cholinergic deficiency hypothesis in delirium by synthesizing evidence on potential pathophysiological pathways. Acetylcholine synthesis involves various precursors, enzymes, and receptors, and dysfunction in these components can lead to delirium. Insults to the brain, like ischemia and immunological stressors, can precipitously alter acetylcholine levels. Imbalances between cholinergic and other neurotransmitter pathways may result in delirium. Furthermore, genetic, enzymatic, and immunological overlaps exist between delirium and dementia related to the cholinergic pathway. Important areas for future research include identifying biomarkers, determining genetic contributions, and evaluating response to cholinergic drugs in delirium. Understanding how the cholinergic pathway relates to delirium may yield innovative approaches in the diagnosis, prevention, and treatment of this common, costly, and morbid condition.

Background Intracranial volume (ICV) has been proposed as a measure of maximum lifetime brain size. Accurate ICV measures require neuroimaging which is not always feasible for epidemiologic investigations. We examined head circumference as a useful surrogate for intracranial volume in older adults.

Methods 99 older adults underwent Magnetic Resonance Imaging (MRI). ICV was measured by Statistical Parametric Mapping 8 (SPM8) software or Functional MRI of the Brain Software Library (FSL) extraction with manual editing, typically considered the gold standard. Head circumferences were determined using standardized tape measurement. We examined estimated correlation coefficients between head circumference and the two MRI-based ICV measurements.

Results Head circumference and ICV by SPM8 were moderately correlated (overall r=0.73, men r=0.67, women r=0.63). Head circumference and ICV by FSL were also moderately correlated (overall r=0.69, men r=0.63, women r=0.49).

Conclusions Head circumference measurement was strongly correlated with MRI-derived ICV. Our study presents a simple method to approximate ICV among older patients, which may prove useful as a surrogate for cognitive reserve in large scale epidemiologic studies of cognitive outcomes. This study also suggests the stability of head circumference correlation with ICV throughout the lifespan.

Background Cognitive and brain reserve theories suggest that aspects of neural architecture or cognitive processes modify the impact of neuropathological processes on cognitive outcomes. While frequently studied in the context of dementia, reserve in delirium is relatively understudied.

Methods We examined the association of three markers of brain reserve (head circumference, MRI-derived brain volume, and leisure time physical activity) and five markers of cognitive reserve (education, vocabulary, cognitive activities, cognitive demand of lifetime occupation, and interpersonal demand of lifetime occupation) and the risk of postoperative delirium in a prospective observational study of 566 older adults free of dementia undergoing scheduled surgery.

Findings Twenty four percent of patients (135/566) developed delirium during the postoperative hospitalization period. Of the reserve markers examined, only the Wechsler Test of Adult Reading (WTAR) was significantly associated with the risk of delirium. A one-half standard deviation better performance on the WTAR was associated with a 38% reduction in delirium risk (P = 0·01); adjusted relative risk of 0·62, 95% confidence interval 0·45–0·85.

Interpretation In this relatively large and well-designed study, most markers of reserve fail to predict delirium risk. The exception to this is the WTAR. Our findings suggest that the reserve markers that are important for delirium may be different from those considered to be important for dementia.