Szofia S. Bullain

Multiple pathologies are common and related to dementia in the oldest-old: The 90+ Study.

Objective: The purpose of this study was to examine the role of multiple pathologies in the expression of dementia in the oldest-old. Methods: A total of 183 participants of The 90+ Study with longitudinal follow-up and autopsy were included in this clinical-pathologic investigation. Eight pathologic diagnoses (Alzheimer disease [AD], microinfarcts, hippocampal sclerosis, macroinfarcts, Lewy body disease, cerebral amyloid angiopathy, white matter disease, and others) were dichotomized. We estimated the odds of dementia in relation to each individual pathologic diagnosis and to the total number of diagnoses. We also examined dementia severity in relation to number of pathologic diagnoses. Results: The presence of multiple pathologic diagnoses was common and occurred more frequently in those with dementia compared with those without dementia (45% vs 14%). Higher numbers of pathologic diagnoses were also associated with greater dementia severity. Participants with intermediate/high AD pathology alone were 3 times more likely to have dementia (odds ratio = 3.5), but those with single non-AD pathologies were 12 times more likely to have dementia (odds ratio = 12.4). When a second pathology was present, the likelihood of dementia increased 4-fold in those with intermediate/high AD pathology but did not change in those with non-AD pathologies, suggesting that pathologies may interrelate in different ways. Conclusions: In the oldest-old, the presence of multiple pathologies is associated with increased likelihood and severity of dementia. The effect of the individual pathologies may be additive or perhaps synergistic and requires further research. Multiple pathologies will need to be targeted to reduce the burden of dementia in the population.

Amyloid imaging and cognitive decline in nondemented oldest-old: The 90+ Study

The goal of this study was to examine cross‐sectional and longitudinal associations between cognitive performance and beta amyloid (Aβ) load determined by florbetapir F18 positron emission tomography (PET) in nondemented oldest‐old.

Age of onset of hypertension and risk of dementia in the oldest-old: The 90+Study

We investigated the association between age of onset of hypertension and dementia risk in an oldest‐old cohort.

Poor physical performance and dementia in the oldest old: the 90+ study.

OBJECTIVE To examine the cross-sectional relationship between physical performance and dementia in the oldest old (those ≥ 90 years of age). DESIGN Cross-sectional study. SETTING The 90+ Study is a population-based, longitudinal, epidemiologic study of aging and dementia performed at the University of California, Irvine, from January 1, 2003, through November 30, 2009. PARTICIPANTS A total of 629 participants from The 90+ Study were included in the study. The mean age was 94 years, and most (72.5%) were women. MAIN OUTCOME MEASURES All-cause dementia, based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria, was the main outcome measure. The independent variables were physical performance measures, including 4-m walk, 5 chair stands, standing balance, and grip strength, each scored from 0 to 4 (0, unable to perform; 4, best performance). Odds of dementia in relation to the physical performance measures were estimated by logistic regression after adjustment for age and sex. RESULTS Poor physical performance in all measures was significantly associated with increased odds of dementia (P< .001). Odds ratios for every unit decrease in physical performance score were 2.1 for 4-m walk, 2.1 for chair stands, 1.9 for standing balance, and 1.7 for grip strength. CONCLUSIONS We found a strong cross-sectional relationship between poor physical performance and dementia in people 90 years and older. Our findings suggest that dementia is a complex neurodegenerative process that may affect physical performance and cognition. Additional research is necessary to determine the temporal relationship between poor physical performance and cognitive dysfunction.

Dementia in the Oldest Old

Purpose of Review: This article discusses some of the unique features of dementia in the oldest old, including some of the most common diagnostic challenges, and potential strategies to overcome them.Recent Findings: Advances include new insight into the role of common risk factors and the effects of multiple underlying neuropathologic features for dementia in the oldest old. In addition, this article contains the latest age-specific normative data for commonly used neuropsychological tests for the oldest old.Summary: The oldest old—people aged 90 years and older—are the fastest-growing segment of society and have the highest rates of dementia in the population. The risk factors, diagnostic challenges, and underlying neuropathologic features of dementia are strikingly different in the 90-years-and-older population compared to younger elderly. Special consideration of these unique features of dementia is necessary when evaluating oldest-old subjects with cognitive impairment.

Communicating mild cognitive impairment diagnoses with and without amyloid imaging

BackgroundMild cognitive impairment (MCI) has an uncertain etiology and prognosis and may be challenging for clinicians to discuss with patients and families. Amyloid imaging may aid specialists in determining MCI etiology and prognosis, but creates novel challenges related to disease labeling.MethodsWe convened a workgroup to formulate recommendations for clinicians providing care to MCI patients.ResultsClinicians should use the MCI diagnosis to validate patient and family concerns and educate them that the patient’s cognitive impairment is not normal for his or her age and education level. The MCI diagnosis should not be used to avoid delivering a diagnosis of dementia. For patients who meet Appropriate Use Criteria after standard-of-care clinical workup, amyloid imaging may position specialists to offer more information about etiology and prognosis. Clinicians must set appropriate expectations, including ensuring that patients and families understand the limitations of amyloid imaging. Communication of negative results should include that patients remain at elevated risk for dementia and that negative scans do not indicate a specific diagnosis or signify brain health. Positive amyloid imaging results should elicit further monitoring and conversations about appropriate advance planning. Clinicians should offer written summaries, including referral to appropriate social services.ConclusionsIn patients with MCI, there is a need to devote considerable time and attention to patient education and shared decision-making. Amyloid imaging may be a tool to aid clinicians. Careful management of patient expectations and communication of scan results will be critical to the appropriate use of amyloid imaging information.

Late-Onset Alzheimer Disease

The oldest-old represent the fastest growing segment of society, and the risk of developing dementia continues to increase with advancing age into the 9th and 10th decades of life. The most common form of dementia in the oldest-old is Alzheimer disease (AD), although there are often mixed pathologies contributing to dementia in addition to amyloid plaques and neurofibrillary tangles. Diagnosing AD in the oldest-old is challenging due to cognitive and physical changes associated with aging. Treatment remains supportive, with current approved medications able to provide modest symptomatic benefit but unable to slow the progression of disease.

Sound Body Sound Mind? Physical Performance and the Risk of Dementia in the Oldest‐Old: The 90+ Study

To examine the longitudinal association between physical performance and risk of dementia in individuals aged 90 and older without dementia.

HISTORY OF VASCULAR DISEASE AND RISK OF DEMENTIA IN THE OLDEST-OLD: THE 90+ STUDY

Background: Coronary artery bypass graft surgery (CABG) is increasingly used in the elderly as a successful treatment for coronary artery disease. However, the long-term association between CABG and dementia risk remains unclear. Methods:We used data from the US Cardiovascular Health Study, a large, prospective population-based study and included 3155 older adults, who were dementia free and had their history of CABG assessed at baseline. Participants were followed up for a median of 6 years (interquartile range 4.7-6.5). We used Cox proportional hazards regression models to examine the association between history of CABG and time to incident all-cause dementia, Alzheimer’s disease (AD), vascular dementia (VaD) and mixed dementia. Our models were adjusted for age, sex, ethnicity, education, baseline hypertension, diabetes and clinical or subclinical cardiovascular disease. Results: History of CABG almost doubled the risk of all-cause dementia (hazard ratio [HR] 1⁄4 1.93, 95% confidence interval [CI] 1⁄4 1.362.74) and almost tripled the risk of mixed dementia (HR 1⁄4 2.73, 95% CI 1⁄4 1.55-4.80) compared to no history of CABG. The associations with AD (HR1⁄4 1.71, 95%CI1⁄4 0.98-2.98) and VaD (HR1⁄4 1.42, 95% CI 1⁄4 0.56-3.65) were in the same direction though statistically not significant.When we compared the risk of incident allcause dementia and its subtypes in those with history of CABG to those with history of percutaneous coronary intervention, HRs suggested that history of CABG may be associated with a higher though statistically not significant risk of all-cause dementia and mixed dementia. However, these analyses were underpowered due to a small number of participants in the comparison group. Conclusions: History of CABG is a long-term risk factor for allcause dementia and mixed dementia. Further research is needed to clarify the mechanisms of this association and to compare CABG to alternative treatments strategies in terms of long-term dementia risk.

COMMUNICATING MILD COGNITIVE IMPAIRMENT DIAGNOSIS WITH AND WITHOUT AMYLOID IMAGING: RECOMMENDATIONS FROM AN EXPERT WORKGROUP

IMPAIRMENT DIAGNOSIS WITH ANDWITHOUT AMYLOID IMAGING: RECOMMENDATIONS FROM AN EXPERT WORKGROUP Joshua D. Grill, Liana G. Apostolova, Szofia S. Bullain, Jeffrey M. Burns, Chelsea Cox, Malcolm Dick, Dean Hartley, Claudia H. Kawas, Sarah Kremen, Jennifer Lingler, Oscar L. Lopez, Nancy Lundebjerg, Mark Mapstone, Aimee Pierce, Gil D. Rabinovici, J Scott Roberts, Seyed Ahmad Sajjadi, Edmond Teng, Jason Karlawish, University of California, Irvine, Irvine, CA, USA; 2 Indiana University School of Medicine, Indianapolis, IN, USA; 3 University of Kansas Alzheimer’s Disease Center, Fairway, KS, USA; Alzheimer’s Association, Chicago, IL, USA; University of California Los Angeles, Los Angeles, CA, USA; 6 University of Pittsburgh, Pittsburgh, PA, USA; 7 American Geriatrics Society, New York, NY, USA; 8 University of Rochester, Rochester, NY, USA; University of California San Francisco, San Francisco, CA, USA; University of Michigan, Ann Arbor, MI, USA; 11 Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, Los Angeles, CA, USA; 12 University of Pennsylvania, Philadelphia, PA, USA. Contact e-mail: jgrill@uci.edu