Tamara G. Fong

Cognitive trajectories after postoperative delirium.

BACKGROUND Delirium is common after cardiac surgery and may be associated with long-term changes in cognitive function. We examined postoperative delirium and the cognitive trajectory during the first year after cardiac surgery. METHODS We enrolled 225 patients 60 years of age or older who were planning to undergo coronary-artery bypass grafting or valve replacement. Patients were assessed preoperatively, daily during hospitalization beginning on postoperative day 2, and at 1, 6, and 12 months after surgery. Cognitive function was assessed with the use of the Mini-Mental State Examination (MMSE; score range, 0 to 30, with lower scores indicating poorer performance). Delirium was diagnosed with the use of the Confusion Assessment Method. We examined performance on the MMSE in the first year after surgery, controlling for demographic characteristics, coexisting conditions, hospital, and surgery type. RESULTS The 103 participants (46%) in whom delirium developed postoperatively had lower preoperative mean MMSE scores than those in whom delirium did not develop (25.8 vs. 26.9, P<0.001). In adjusted models, those with delirium had a larger drop in cognitive function (as measured by the MMSE score) 2 days after surgery than did those without delirium (7.7 points vs. 2.1, P<0.001) and had significantly lower postoperative cognitive function than those without delirium, both at 1 month (mean MMSE score, 24.1 vs. 27.4; P<0.001) and at 1 year (25.2 vs. 27.2, P<0.001) after surgery. With adjustment for baseline differences, the between-group difference in mean MMSE scores was significant 30 days after surgery (P<0.001) but not at 6 or 12 months (P=0.056 for both). A higher percentage of patients with delirium than those without delirium had not returned to their preoperative baseline level at 6 months (40% vs. 24%, P=0.01), but the difference was not significant at 12 months (31% vs. 20%, P=0.055). CONCLUSIONS Delirium is associated with a significant decline in cognitive ability during the first year after cardiac surgery, with a trajectory characterized by an initial decline and prolonged impairment. (Funded by the Harvard Older Americans Independence Center and others.).

Delirium in elderly adults: diagnosis, prevention and treatment

Delirium is a common and serious acute neuropsychiatric syndrome with core features of inattention and global cognitive dysfunction. The etiologies of delirium are diverse and multifactorial and often reflect the pathophysiological consequences of an acute medical illness, medical complication or drug intoxication. Delirium can have a widely variable presentation, and is often missed and underdiagnosed as a result. At present, the diagnosis of delirium is clinically based and depends on the presence or absence of certain features. Management strategies for delirium are focused on prevention and symptom management. This article reviews current clinical practice in delirium in elderly individuals, including the diagnosis, treatment, outcomes and economic impact of this syndrome. Areas of future research are also discussed.

Delirium accelerates cognitive decline in Alzheimer disease.

Objective: To examine the impact of delirium on the trajectory of cognitive function in a cohort of patients with Alzheimer disease (AD). Methods: A secondary analysis of data collected from a large prospective cohort, the Massachusetts Alzheimer’s Disease Research Center’s patient registry, examined cognitive performance over time in patients who developed (n = 72) or did not develop (n = 336) delirium during the course of their illnesses. Cognitive performance was measured by change in score on the Information-Memory-Concentration (IMC) subtest of the Blessed Dementia Rating Scale. Delirium was identified using a previously validated chart review method. Using linear mixed regression models, rates of cognitive change were calculated, controlling for age, sex, education, comorbid medical diagnoses, family history of dementia, dementia severity score, and duration of symptoms before diagnosis. Results: A significant acceleration in the slope of cognitive decline occurs following an episode of delirium. Among patients who developed delirium, the average decline at baseline for performance on the IMC was 2.5 points per year, but after an episode of delirium there was further decline to an average of 4.9 points per year (p = 0.001). Across groups, the rate of change in IMC score occurred about three times faster in those who had delirium compared to those who did not. Conclusions: Delirium can accelerate the trajectory of cognitive decline in patients with Alzheimer disease (AD). The information from this study provides the foundation for future randomized intervention studies to determine whether prevention of delirium might ameliorate or delay cognitive decline in patients with AD.

Delirium: An independent predictor of functional decline after cardiac surgery

OBJECTIVES: To determine whether patients who developed delirium after cardiac surgery were at risk of functional decline.

Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

BACKGROUND Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). OBJECTIVE To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. DESIGN Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimers Disease Research Center (MADRC) patient registry. SETTING Community-based. PARTICIPANTS 771 persons aged 65 years or older with a clinical diagnosis of AD. MEASUREMENTS Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). RESULTS Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. LIMITATIONS Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. CONCLUSION Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may represent an important strategy for reducing adverse outcomes in this population.

Hippocampal hyperperfusion in Alzheimer's disease.

Many of the regions with the earliest atrophy in Alzheimers Disease (AD) do not show prominent deficits on functional imaging studies of flow or metabolism. This paradox may provide unique insights into the pathophysiology of AD. We sought to examine the relationship between function and atrophy in AD using MRI blood flow and anatomic imaging. 22 subjects diagnosed with AD, mean Mini Mental State Exam (MMSE) score 22.2, and 16 healthy elderly controls were imaged with a volumetric arterial spin labeling blood flow MRI technique and an anatomical imaging method using the identical spatial resolution, image orientation, and spatial encoding strategy. Cerebral blood flow (CBF) and gray matter (GM) maps derived from the imaging were transformed to a standard anatomical space. GM and CBF maps were tested for significant differences between groups. Additionally, images were tested for regions with significant mismatch of the CBF and GM differences between groups. CBF was significantly lower in the bilateral precuneus, parietal association cortex and the left inferior temporal lobe but was non-significantly increased in the hippocampus and other medial temporal structures. After correction for GM loss, CBF was significantly elevated in the hippocampus and other medial temporal structures. The hippocampus and other regions affected early in AD are characterized by elevated atrophy-corrected perfusion per cm(3) of tissue. This suggests compensatory or pathological elevation of neural activity, inflammation, or elevated production of vasodilators.

Hospitalization in Community-Dwelling Persons with Alzheimer’s Disease: Frequency and Causes

OBJECTIVES: To examine the rates of and risk factors for acute hospitalization in a prospective cohort of older community‐dwelling patients with Alzheimers disease (AD).

The interface between delirium and dementia in elderly adults

Delirium and dementia are two of the most common causes of cognitive impairment in older populations, yet their interrelation remains poorly understood. Previous studies have shown that dementia is the leading risk factor for delirium and that delirium is an independent risk factor for subsequent development of dementia. However, a major area of controversy is whether delirium is simply a marker of vulnerability to dementia, whether the effect of delirium is solely related to its precipitating factors, or whether delirium itself can cause permanent neuronal damage and lead to dementia. Ultimately, all of these hypotheses are likely to be true. Emerging evidence from epidemiological, clinicopathological, neuroimaging, biomarker, and experimental studies lends support to a strong relation between delirium and dementia, and to both shared and distinct pathological mechanisms. New preventive and therapeutic approaches that target delirium might offer a sought-after opportunity for early intervention, preservation of cognitive reserve, and prevention of irreversible cognitive decline in ageing.

Aging, Brain Disease, and Reserve: Implications for Delirium

Cognitive and brain reserve are well studied in the context of age-associated cognitive impairment and dementia. However, there is a paucity of research that examines the role of cognitive or brain reserve in delirium. Indicators (or proxy measures) of cognitive or brain reserve (such as brain size, education, and activities) pose challenges in the context of the long prodromal phase of Alzheimer disease but are diminished in the context of delirium, which is of acute onset. This article provides a review of original articles on cognitive and brain reserve across many conditions affecting the central nervous system, with a focus on delirium. The authors review current definitions of reserve. The authors identify indicators for reserve used in earlier studies and discuss these indicators in the context of delirium. The authors highlight future research directions to move the field ahead. Reserve may be a potentially modifiable characteristic. Studying the role of reserve in delirium can advance prevention strategies for delirium and may advance knowledge of reserve and its role in aging and neuropsychiatric disease generally.

Telephone Interview for Cognitive Status: Creating a crosswalk with the Mini-Mental State Examination

Brief cognitive screening measures are valuable tools for both research and clinical applications. The most widely used instrument, the Mini‐Mental State Examination (MMSE), is limited in that it must be administered face‐to‐face, cannot be used in participants with visual or motor impairments, and is protected by copyright. Screening instruments such as the Telephone Interview for Cognitive Status (TICS) were developed to provide a valid alternative, with comparable cut‐point scores to rate global cognitive function.