Researchers Find New Method to Measure Cognitive Impairment, Dementia

This article, " Health-Deficit Accumulation Affects Risk for Mild Cognitive Impairment, Dementia," was originally published in NeurologyLive.

Using a frailty index score could enable clinicians to identify patients at risk for cognitive dysfunction, making it an important marker for prognostic value.

Newly published data suggests health-deficit accumulation, specifically among older Americans, affects the likelihood of progressive cognitive impairment, as well as the likelihood of cognitive improvement independent of the APOE ε4 allele.

Lead author David D. Ward, PhD, postdoctoral fellow, geriatric medicine research, Centre for Health Care of the Elderly, Nova Scotia Healthy Authority, and colleagues calculated a frailty index score using the deficit-accumulation approach in participants aged 50 years and older from the National Alzheimer’s Coordinating Center (NACC).

Among those not cognitively impaired (NCI; n = 9773), each 0.1 increment increase in score were associated with a higher risk of developing mild cognitive impairment (MCI) and a higher risk of developing dementia.

In total, there were 14,490 participants in the study with a mean age of 72.2 years. In the MCI subsample (n = 4717) at baseline, there was a higher degree of frailty that was associated with a lower probability of being reclassified as NCI from MCI, a higher risk of returning to MCI in those who were reclassified as NCI, and a higher risk of progressing to dementia.

"We conclude that frailty is a key risk factor for age-related cognitive dysfunction and dementia, representing both a target for interventions aimed at the prevention of age-related cognitive impairment and possible prognostic marker among those who have MCI,” the authors wrote.

The score is a health-state measure, incorporating information from multiple physiological systems, and closely reflects an individual’s risk for adverse health events and mortality independently of chronological age. A higher frailty index score indicated accumulation of more age-related health deficits while approximating biological age.

The researchers aimed to detail the dynamic nature of cognitive functioning by calculating the likelihood of transitions between cognitive states in both directions over a 12-month period. Decline of cognitive function was considered forward transition, whereas improvement of cognitive functioning was defined as backwards transition.

The investigators also assessed whether frailty index score and APOE ε4 allele carrier status exerted independent or interactive effects on cognitive-state transition probabilities.

They found no statistically significant interactions between these variables for any transition in the NCI subsample. However, in the MCI subsample, the association of the frailty index score and the risk of progressing to dementia was significantly weaker in those carrying an APOE ε4 allele than in non-carriers (interaction hazard risk [HR], 0.88; 95% CI, 0.80–0.97).

There were no meaningful differences in these associations when participants whose race was other than white were removed from the analytical sample. Notably, associations of the frailty index score with transition probabilities did not differ significantly between men and women.

Over 12 months, NCI subsample participants maintained their prior state 43,086 times (90.6%) and transitioned between states 4491 times (9.4%), 3086 (68.7%) of which were transitions between cognitive states, with 1405 (31.3%) transitions to death. Of the cognitive-state transitions in the NCI subsample, 80.9% were forward transitions, and 19.1% were backward transitions. In the MCI subsample, 70.5% were forward compared to 29.5% who experienced backwards transition.

"This work supports an emerging conceptualization of late-onset dementia as a complex outcome of aging that often is intimately related to an individual’s general health, as well as genetic risk factors,” the authors wrote.

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Particulate Matter Increases Future Risk of Alzheimer Disease

Progressive brain atrophy known to be predictive of Alzheimer disease (AD) is linked to late-life exposure to particulate matter with aerodynamic diameters <2.5-μm (PM2.5), according to new research.

Longitudinal analyses showed that for each interquartile range (IQR) increase (IQR, 2.82- μg/m3) of PM2.5, the associated risk of developing AD increased by 24% (hazard ratio [HR], 1.24; 95% CI, 1.14–1.34) over a 5-year period, as assessed by increased AD pattern similarity (AD-PS) scores. This association remained within levels of PM2.5 below US regulatory standards (<12-μg/m3).

Principal author Diana Younan, PhD, research associate, University of Southern California, stated in a related release that the “findings have important public health implications because not only did we find brain shrinkage in women exposed to the highest levels of PM2.5 pollution but we also found it in women exposed to levels lower than those that the EPA considers safe.”

Younan and colleagues investigated data from 1365 women free of dementia with a mean age of 77.9 years (standard deviation [SD], 2.7) that participated in the WHIMS Magnetic Resonance Imaging (WHIMS MRI) study.

MRI data at baseline and after 5 years was investigated. AD-PS scores—which have been shown to be associated with known risk factors of AD and poor cognitive function—were developed by a supervised machine learning algorithm by comparison of MRI data from the AD Neuroimaging Initiative of gray matter atrophy in areas vulnerable to AD such as the amygdala, hippocampus, thalamus, midbrain, parahippocampal gyrus, and inferior temporal lobe areas.

In longitudinal analysis, IQR-increments were significantly associated with a 0.031 (β = 0.031; 95% CI, 0.017–0.046) increase in AD-PS score.

In fully adjusted models the association was 0.026 (95% CI, 0.009–0.043), which correlates to the 24% increase of AD risk. This association remained after adjusting for socio-demographics, lifestyle, and clinical characteristics including cerebrovascular factors such as white matter lesion volume and stroke, challenging previous studies that have proposed a cerebrovascular mechanism of PM2.5 damage leading to brain atrophy.

Instead, Younan and colleagues favor the theorized mechanism that PM2.5 directly contributes to the neurodegenerative process of dementia via a neurotoxic effect on brain structure.

Sensitivity analyses confirmed the positive association between PM2.5 and AD-PS score after adjusting for baseline AD-PS scores. No association was seen between PM2.5 and baseline AD-PS score in cross sectional analyses (β = –0.004; 95% CI, –0.019 to 0.011).

Previous analyses of WHIMS MRI include region-of-interest analyses that showed residence in areas with higher PM2.5 was associated with smaller total brain and white matter volumes, and that residing in places with >12-μg/m3 concentrations of PM2.5 increased the risk of global cognitive decline by 81% and all-cause dementia by 92%.

Younan and colleagues call for future studies “to fully investigate whether the neurodegenerative effects of late-life exposures to airborne particles may be contributed by or independent of cerebrovascular damage before or during late life...to replicate these results and to thoroughly explore other measures of cerebrovascular damage that may not be captured by white matter lesions and were not explored in our study (e.g., microbleeds; lacunar infarcts).”

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Sandra Day O’Connor’s farewell letter is a plea for country before party

By Ephrat Livni22 minutes ago


Sandra Day O’Connor is not an average American, and there’s plenty of evidence to support this contention.


For one, she was the first woman to serve on the US Supreme Court, appointed in 1981 by Ronald Reagan. And she’s remained active in public life even after her retirement in 2006, committed to advancing civic learning and sharing her passion for the US Constitution and the government it lays out. Today (Oct. 23), she announced she’s stepping out of the limelight because she’s been diagnosed with the beginning stages of dementia and probably has Alzheimer’s disease.


In a sort of farewell letter to the nation (pdf), she urges the rest of us to take up the cause of active citizenship that she can no longer devote herself to entirely, writing:


I feel so strongly about the topic because I’ve seen first-hand how vital it is for all citizens to understand our Constitution and unique system of government, and participate actively in their communities. It is through this shared understanding of who we are that we can follow the approaches that have served us best over time–working collaboratively together in communities and in government to solve problems, putting country and the common good above party and self-interest, and holding our key governmental institutions accountable.


O’Connor, 88, is a pioneer in more ways than one. In 2010, she started iCivics, a non-profit institution that provides free civics games and tutorials to students online and creates lesson plans for teachers in classrooms. On the site, she explains the project, saying, “The practice of democracy is not passed down through our gene pool. It must be taught and learned anew by each generation of citizens.”


In her letter today O’Connor called on all Americans to commit to the project of democracy by engaging in their communities and participating. “It’s not enough to understand, you’ve got to do something,” she writes.


If anyone is in a position to say this, it’s O’Connor, who as a self-described “young cowgirl from the Arizona desert” never could have imagined becoming the first woman on the high court. “I hope that I have inspired young people about civic engagement and helped pave the pathway for women who may have faced obstacles pursuing their careers,” she writes. “While the final chapter of my life with dementia may be trying, nothing has diminished my gratitude and deep appreciation for the countless blessings in my life.”


In response to O’Connor’s announcement, chief justice John Roberts issued a brief statement (pdf), writing that he is saddened by the news but “not at all surprised” that she used the moment “to think of our country first, and to urge an increased commitment to civics education, a cause to which she devoted so much of her time and indomitable energy.” He called her “a towering figure in the history of the United States and indeed the world” and “a role model not only for girls and women, but for all those committed to equal justice under law.”


Roberts concluded, that “no illness or condition can take away the inspiration she provides for those who will follow the many paths she has blazed.” It’s a sentiment that everyone can agree with—whatever their political affiliation.

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