Transitions Between Mild Cognitive Impairment, Dementia, and Mortality: The Importance of Olfaction.

BACKGROUND: The existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear. METHODS: Drawing data from the Rush Memory and Aging Project (N = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0-16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies. RESULTS: Higher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82-0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86-0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02-1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states. CONCLUSIONS: Findings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration.

Longitudinal associations between C-reactive protein and cognitive performance in normative cognitive ageing and dementia.

BACKGROUND: systemic inflammation appears to play an important role in the pathogenesis and expression of Alzheimer's disease and other dementias. Previous research has found that elevated levels of serum C-reactive protein (CRP) is associated with poorer cognitive functioning and increased risk for dementia. However, most studies are limited by single CRP measurements, which fail to capture long-term inflammatory exposures or dynamic changes in inflammation and cognition which may occur across repeated measurements. METHODS: using data from 3,563 older adults aged 65-101 from the Health and Retirement Study, we examined bivariate changes in CRP and cognition measured repeatedly over a 10-year follow-up. Bivariate multilevel models estimated the effect of time-varying CRP on cognition among cognitively healthy older adults and in a subset of 427 participants who reported incident dementia onset during the follow-up period. RESULTS: in cognitively healthy participants, CRP was associated with lower level of cognitive functioning, but not rate of change over time. This effect was significant in participants under 80 years of age (b = -0.09, standard error (SE) = 0.05, P = 0.04), but not in older participants. In participants with incident dementia, those with higher CRP experienced smaller rates of cognitive decline, leading up to dementia diagnosis. CONCLUSIONS: elevated levels of CRP predict poorer cognition and increased dementia risk in cognitively healthy adults under the age of 80. Conversely, increased CRP may confer protective effects on cognition in the prodromal stage of dementia.

The Importance of Engaging in Physical Activity in Older Adulthood for Transitions Between Cognitive Status Categories and Death: A Coordinated Analysis of 14 Longitudinal Studies.

BACKGROUND: Given increasing incidence of cognitive impairment and dementia, further understanding of modifiable factors contributing to increased healthspan is crucial. Extensive literature provides evidence that physical activity (PA) delays the onset of cognitive impairment; however, it is unclear whether engaging in PA in older adulthood is sufficient to influence progression through cognitive status categories. METHOD: Applying a coordinated analysis approach, this project independently analyzed 14 longitudinal studies (NTotal = 52 039; mean baseline age across studies = 69.9-81.73) from North America and Europe using multistate survival models to estimate the impact of engaging in PA on cognitive status transitions (nonimpaired, mildly impaired, severely impaired) and death. Multinomial regression models were fit to estimate life expectancy (LE) based on American PA recommendations. Meta-analyses provided the pooled effect sizes for the role of PA on each transition and estimated LEs. RESULTS: Controlling for baseline age, sex, education, and chronic conditions, analyses revealed that more PA is significantly associated with decreased risk of transitioning from nonimpaired to mildly impaired cognitive functioning and death, as well as substantially longer LE. Results also provided evidence for a protective effect of PA after onset of cognitive impairment (eg, decreased risk of transitioning from mild-to-severe cognitive impairment; increased likelihood of transitioning backward from severe-to-mild cognitive impairment), though between-study heterogeneity suggests a less robust association. CONCLUSIONS: These results yield evidence for the importance of engaging in PA in older adulthood for cognitive health, and a rationale for motivating older adults to engage consistently in PA.

Variability and Coupling of Olfactory Identification and Episodic Memory in Older Adults.

OBJECTIVES: To determine whether assessment-to-assessment fluctuations in episodic memory (EM) reflect fluctuations in olfaction over time. METHODS: Within-person coupled variation in EM and the Brief Smell Identification Test (BSIT) was examined in 565 participants aged 58-106 with autopsy data from the Rush Memory and Aging Project. A growth model for up to 15 years of EM data, with BSIT as time-varying covariate, was estimated accounting for main effects of sex, education, ε4 allele, and Alzheimer's disease (AD) pathology, BSIT and time-varying BSIT, as well as the interaction between AD pathology and time-varying BSIT. RESULTS: Individuals with higher BSIT scores (b = .01, standard error [SE] = .004, p = .009) had slower declines in EM. High AD pathology (b = -.06, SE = .02, p = .001) was associated with more rapid declines in EM. The association between time-specific fluctuations in EM and BSIT differed by level of AD pathology (b = .08, SE = .034, p = .028), with a higher EM-BSIT association at higher levels of pathology. DISCUSSION: BSIT and EM fluctuate together over measurement occasions, particularly for individuals with AD pathology. Repeated intraindividual measurements provide information that could lead to early detection and inexpensive monitoring of accumulating AD pathology.

A safety-net antibiotic prescription for otitis media: the effects of a PBRN study on patients and practitioners.

Pediatricians can decrease antibiotic use by treating acute otitis media (AOM) with a safety-net antibiotic prescription (SNAP). This study assessed whether the practitioners of the Practice-Based Research Network who participated in the study continued to use the SNAP and report a 60-day follow-up of the study patients. Charts were reviewed of study patients for 60 days following study enrollment. A survey on antibiotic use for AOM was mailed to the 17 study practitioners (SP) and 30 randomly selected community pediatricians (CP). Eight of the SP used the SNAP more than 20 times over the year following the study vs 1 of the CP. Sixty-two percent of patients never received antibiotics. The recurrence/relapse rate was greater in children younger than 2 years old compared to those older, 34% vs 10%. Practitioners who participate in a Practice-Based Research Network study are more likely to use a study intervention than others.