Impaired olfaction is associated with cognitive decline and neurodegeneration in the brain

ObjectiveWe aimed to examine whether impaired olfaction is associated with cognitive decline and indicators of neurodegeneration in the brain of dementia-free older adults.MethodsWithin the Rush Memory and Aging Project, 380 dementia-free participants (mean age = 78 years) were followed for up to 15 years, and underwent MRI scans. Olfactory function was assessed using the Brief Smell Identification Test (B-SIT) at baseline, and categorized as anosmia (B-SIT <6), hyposmia (B-SIT 6–10 in men and 6–10.25 in women), and normal (B-SIT 10.25–12 in men and 10.5–12 in women). Cognitive function was annually assessed with a battery of 21 tests, from which composite scores were derived. Structural total and regional brain volumes were estimated. Data were analyzed using linear regression and mixed-effects models.ResultsAt study entry, 138 (36.3%) had normal olfactory function, 213 (56.1%) had hyposmia, and 29 (7.6%) had anosmia. In multiadjusted mixed-effects models, hyposmia (β = −0.03, 95% confidence interval [CI] −0.05 to −0.02) and anosmia (β = −0.13, 95% CI −0.16 to −0.09) were associated with faster rate of cognitive decline compared to normal olfaction. On MRI, impaired olfaction (hyposmia or anosmia) was related to smaller volumes of the hippocampus (β = −0.19, 95% CI −0.33 to −0.05), and in the entorhinal (β = −0.16, 95% CI −0.24 to −0.08), fusiform (β = −0.45, 95% CI −0.78 to −0.14), and middle temporal (β = −0.38, 95% CI −0.72 to −0.01) cortices.ConclusionImpaired olfaction predicts faster cognitive decline and might indicate neurodegeneration in the brain among dementia-free older adults.

Download Full-text

4489 Association between surgery with general anesthesia and cognitive decline in older adults: analysis using shared parameter models for informative dropout

Journal of Clinical and Translational Science ◽

10.1017/cts.2020.168 ◽

2020 ◽

Vol 4 (s1) ◽

pp. 45-45

Author(s):

Phillip Schulte ◽

Katrina Devick ◽

Juraj Sprung

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Mixed Effects ◽

Cognitive Outcomes ◽

Drop Out ◽

Mixed Effects Models ◽

Z Score ◽

Informative Dropout ◽

Linear Mixed Effects Models ◽

Linear Mixed Effects

OBJECTIVES/GOALS: Recent studies have assessed the association between surgery with general anesthesia and cognitive decline in longitudinal cohorts of older adults. Patients diagnosed with dementia more frequently drop out of these longitudinal studies or are unable to complete the test battery. We revisit this aim with focus on methods for informative dropout. METHODS/STUDY POPULATION: We use data from the Mayo Clinic Study of Aging (MCSA), a longitudinal epidemiological study of the prevalence, incidence, and risk factors for mild cognitive impairment (MCI) and dementia. Our primary outcome of interest was global cognitive z-score, assessed at study visits every 15 months. We implement linear mixed effects models to assess the association between post-enrollment exposure to surgery/anesthesia and subsequent cognitive decline trajectories. Demented patients more frequently drop out of MCSA, so, subjects with the worst cognitive outcomes are unobserved and missing data may be informative. Since this missingness may be missing not at random, we use shared parameter models to analyze continuous cognitive outcomes while jointly modeling time to dementia. RESULTS/ANTICIPATED RESULTS: A total 1948 subjects, non-demented at baseline, from the MCSA were included. Median age was 79, 51% of subjects were male, and 16% had MCI at enrollment. Among median follow-up of 4 study visits over median 5.4 years, 172 patients developed dementia and dropped out from further assessments of cognitive function. In adjusted linear mixed effects models, our data suggest post-enrollment exposure to surgery/anesthesia is associated with a decline in cognitive function over time (change in slope = −0.07 standard deviations of cognitive z-score per year, 95%CI = −0.08, −0.05, p<.001). After adjusting for informative dropout using shared parameter models, surgery/anesthesia is associated with greater cognitive decline (change in slope = −0.14 per year, 95%CI = −0.16, −0.12, p<.001). DISCUSSION/SIGNIFICANCE OF IMPACT: We revisited a prior analysis by our group with consideration of informative dropout. Subjects who dropout due to dementia may have different trajectories of cognitive decline compared to non-demented subjects. Shared parameter models estimate the association between surgery/anesthesia and cognitive decline accounting for informative dropout.

Download Full-text

Cognitive trajectories of patients with focal ß-amyloid deposition

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00787-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Si Eun Kim ◽

Byungju Lee ◽

Hyemin Jang ◽

Juhee Chin ◽

Ching Soong Khoo ◽

...

Keyword(s):

Cognitive Decline ◽

Neuropsychological Tests ◽

Mixed Effects ◽

Amnestic Mild Cognitive Impairment ◽

Emission Tomography ◽

Amyloid Pet ◽

Cognitive Level ◽

Visual Rating ◽

Positron Emission ◽

The Brain

Abstract Background The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition. Methods We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer’s disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group. Results Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7–9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1–3 or 4–6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex. Conclusions When predicting cognitive decline of patients with focal Aß deposition, the patients’ cognitive level, extent, and location of the focal involvement are important.

Download Full-text

Association of anticholinergic medications and AD biomarkers with incidence of MCI among cognitively normal older adults

Neurology ◽

10.1212/wnl.0000000000010643 ◽

2020 ◽

Vol 95 (16) ◽

pp. e2295-e2304 ◽

Cited By ~ 1

Author(s):

Alexandra J. Weigand ◽

Mark W. Bondi ◽

Kelsey R. Thomas ◽

Noll L. Campbell ◽

Douglas R. Galasko ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Mixed Effects ◽

Mixed Effects Models ◽

Linear Mixed Effects Models ◽

Cognitively Normal ◽

Linear Mixed Effects ◽

Anticholinergic Medications ◽

Increased Risk ◽

Risk Of Progression

ObjectiveTo determine the cognitive consequences of anticholinergic medications (aCH) in cognitively normal older adults as well as interactive effects of genetic and CSF Alzheimer disease (AD) risk factors.MethodsA total of 688 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative were evaluated (mean age 73.5 years, 49.6% female). Cox regression examined risk of progression to mild cognitive impairment (MCI) over a 10-year period and linear mixed effects models examined 3-year rates of decline in memory, executive function, and language as a function of aCH. Interactions with APOE ε4 genotype and CSF biomarker evidence of AD pathology were also assessed.ResultsaCH+ participants had increased risk of progression to MCI (hazard ratio [HR] 1.47, p = 0.02), and there was a significant aCH × AD risk interaction such that aCH+/ε4+ individuals showed greater than 2-fold increased risk (HR 2.69, p < 0.001) for incident MCI relative to aCH−/ε4−), while aCH+/CSF+) individuals demonstrated greater than 4-fold (HR 4.89, p < 0.001) increased risk relative to aCH−/CSF−. Linear mixed effects models revealed that aCH predicted a steeper slope of decline in memory (t = −2.35, p = 0.02) and language (t = −2.35, p = 0.02), with effects exacerbated in individuals with AD risk factors.ConclusionsaCH increased risk of incident MCI and cognitive decline, and effects were significantly enhanced among individuals with genetic risk factors and CSF-based AD pathophysiologic markers. Findings underscore the adverse impact of aCH medications on cognition and the need for deprescribing trials, particularly among individuals with elevated risk for AD.

Download Full-text

Functional dedifferentiation of the brain during healthy aging

Journal of Neurophysiology ◽

10.1152/jn.00039.2020 ◽

2020 ◽

Vol 123 (4) ◽

pp. 1279-1282

Author(s):

Divyangana Rakesh ◽

Kavisha B. Fernando ◽

Sina Mansour L.

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Cognitive Deficits ◽

Theoretical Approach ◽

Healthy Aging ◽

Functional Specialization ◽

The Novel ◽

Graph Theoretical Approach ◽

Future Work ◽

The Brain

Nonpathological aging is associated with significant cognitive deficits. Thus, the underlying neurobiology of aging-associated cognitive decline warrants investigation. In a recent study, Chong et al. (Chong JSX, Ng KK, Tandi J, Wang C, Poh J-H, Lo JC, Chee MWL, Zhou JH. J Neurosci 39: 5534–5550, 2019) provided insights into the association between cognitive decline and the loss of functional specialization in the brains of older adults. Here, we introduce the novel graph theoretical approach utilized and discuss the significance of their findings and broader implications on aging. We also provide alternate perspectives of their findings and suggest directions for future work.

Download Full-text

ASSOCIATIONS BETWEEN PERSONALITY TRAITS AND COGNITIVE RESILIENCE IN OLDER ADULTS

Innovation in Aging ◽

10.1093/geroni/igz038.2860 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S778-S778

Author(s):

Eileen K Graham ◽

Bryan James ◽

Daniel K Mroczek

Keyword(s):

Older Adults ◽

Individual Differences ◽

Cognitive Decline ◽

Personality Traits ◽

Mixed Effects ◽

Linear Mixed Effects ◽

Before And After ◽

Diagnosis Of Dementia ◽

Stage 1 ◽

Existing Data

Abstract There are considerable individual differences in the rates of cognitive decline across later adulthood. Personality traits are one set of factors that may account for some of these differences. The current project explores whether personality traits are associated with trajectories of cognitive decline, and whether the associations are different before and after a diagnosis of dementia. The data will be analyzed using linear mixed effects regression. Across these goals is a focus on replicability and generalizability. Each of these questions will be addressed in four independent longitudinal studies of aging (EAS, MAP, ROS, SATSA), then meta-analyzed, thus providing an estimate of the replicability of our results. This study is part of a registered report of existing data that is currently under stage 1 review.

Download Full-text

O1-11-06: IMPAIRED OLFACTORY FUNCTION IS ASSOCIATED WITH ACCELERATED COGNITIVE DECLINE AND NEURODEGENERATION IN THE BRAIN

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.2395 ◽

2006 ◽

Vol 14 (7S_Part_4) ◽

pp. P248-P249

Author(s):

Christina S. Dintica ◽

Anna Marseglia ◽

Debora Rizzuto ◽

Rui Wang ◽

Janina Seubert ◽

...

Keyword(s):

Cognitive Decline ◽

Olfactory Function ◽

The Brain

Download Full-text

The Effect of Active Plus, a Computer-Tailored Physical Activity Intervention, on the Physical Activity of Older Adults with Chronic Illness(es)—A Cluster Randomized Controlled Trial

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17072590 ◽

2020 ◽

Vol 17 (7) ◽

pp. 2590

Author(s):

Esmee Volders ◽

Catherine A. W. Bolman ◽

Renate H. M. de Groot ◽

Peter Verboon ◽

Lilian Lechner

Keyword(s):

Physical Activity ◽

Older Adults ◽

Randomized Controlled Trial ◽

Controlled Trial ◽

Mixed Effects ◽

Mixed Effects Models ◽

Linear Mixed Effects Models ◽

Linear Mixed Effects ◽

Randomized Controlled ◽

Objectively Measured

eHealth interventions aimed at improving physical activity (PA) can reach large populations with few resources and demands on the population as opposed to centre-based interventions. Active Plus is a proven effective computer-tailored PA intervention for the older adult population focusing on PA in daily life. This manuscript describes the effects of the Active Plus intervention (N = 260) on PA of older adults with chronic illnesses (OACI), compared to a waiting list control group (N = 325). It was part of a larger randomized controlled trial (RCT) on the effects of the Active Plus intervention on cognitive functioning. OACI (≥65 years) with at least one chronic illness were allocated to one of the conditions. Intervention group participants received PA advice. Baseline and follow-up measurements were assessed after 6 and 12 months. Intervention effects on objectively measured light PA (LPA) and moderate-to-vigorous PA (MVPA) min/week were analysed with multilevel linear mixed-effects models adjusted for the clustered design. Intervention effects on self-reported MVPA min/week on common types of PA were analysed with two-part generalized linear mixed-effects models adjusted for the clustered design. The dropout rate was 19.1% after 6 months and 25.1% after 12 months. Analyses showed no effects on objectively measured PA. Active Plus increased the likelihood to perform self-reported cycling and gardening at six months and participants who cycled increased their MVPA min/week of cycling. Twelve months after baseline the intervention increased the likelihood to perform self-reported walking and participants who cycled at 12 months increased their MVPA min/week of cycling. Subgroup analyses showed that more vulnerable participants (higher degree of impairment, age or body mass index) benefitted more from the intervention on especially the lower intensity PA outcomes. In conclusion, Active Plus only increased PA behaviour to a limited extent in OACI 6 and 12 months after baseline measurements. The Active Plus intervention may yet be not effective enough by itself in OACI. A blended approach, where this eHealth intervention and face-to-face contact are combined, is advised to improve the effects of Active Plus on PA in this target group.

Download Full-text

Kernels for Longitudinal Data with Variable Sequence Length and Sampling Intervals

Neural Computation ◽

10.1162/neco_a_00164 ◽

2011 ◽

Vol 23 (9) ◽

pp. 2390-2420 ◽

Cited By ~ 1

Author(s):

Zhengdong Lu ◽

Todd K. Leen ◽

Jeffrey Kaye

Keyword(s):

Longitudinal Data ◽

Cognitive Decline ◽

Likelihood Ratio ◽

Neuropsychological Tests ◽

Motor Behavior ◽

Generative Models ◽

Mixed Effects ◽

Mixed Effects Models ◽

Sequence Length ◽

Better Than

We develop several kernel methods for classification of longitudinal data and apply them to detect cognitive decline in the elderly. We first develop mixed-effects models, a type of hierarchical empirical Bayes generative models, for the time series. After demonstrating their utility in likelihood ratio classifiers (and the improvement over standard regression models for such classifiers), we develop novel Fisher kernels based on mixture of mixed-effects models and use them in support vector machine classifiers. The hierarchical generative model allows us to handle variations in sequence length and sampling interval gracefully. We also give nonparametric kernels not based on generative models, but rather on the reproducing kernel Hilbert space. We apply the methods to detecting cognitive decline from longitudinal clinical data on motor and neuropsychological tests. The likelihood ratio classifiers based on the neuropsychological tests perform better than than classifiers based on the motor behavior. Discriminant classifiers performed better than likelihood ratio classifiers for the motor behavior tests.

Download Full-text

Multi-site Pain Is Associated with Long-term Patient-Reported Outcomes in Older Adults with Persistent Back Pain

Pain Medicine ◽

10.1093/pm/pny270 ◽

2019 ◽

Vol 20 (10) ◽

pp. 1898-1906 ◽

Cited By ~ 3

Author(s):

Sean D Rundell ◽

Kushang V Patel ◽

Melissa A Krook ◽

Patrick J Heagerty ◽

Pradeep Suri ◽

...

Keyword(s):

Older Adults ◽

Back Pain ◽

Pain Intensity ◽

Mixed Effects ◽

Mixed Effects Models ◽

Widespread Pain ◽

Pain Site ◽

Multisite Pain ◽

Persistent Back Pain

AbstractObjectiveTo estimate the prevalence of co-occurring pain sites among older adults with persistent back pain and associations of multisite pain with longitudinal outcomes.DesignSecondary analysis of a cohort study.SettingThree integrated health systems in the United States.SubjectsEight hundred ninety-nine older adults with persistent back pain.MethodsParticipants reported pain in the following sites: stomach, arms/legs/joints, headaches, neck, pelvis/groin, and widespread pain. Over 18 months, we measured back-related disability (Roland Morris, scored 0–24), pain intensity (11-point numerical rating scale), health-related quality of life (EuroQol-5D [EQ-5D], utility from 0–1), and falls in the past three weeks. We used mixed-effects models to test the association of number and type of pain sites with each outcome.ResultsNearly all (N = 839, 93%) respondents reported at least one additional pain site. There were 216 (24%) with one additional site and 623 (69%) with multiple additional sites. The most prevalent comorbid pain site was the arms/legs/joints (N = 801, 89.1%). Adjusted mixed-effects models showed that for every additional pain site, RMDQ worsened by 0.65 points (95% confidence interval [CI] = 0.43 to 0.86), back pain intensity increased by 0.14 points (95% CI = 0.07 to 0.22), EQ-5D worsened by 0.012 points (95% CI = –0.018 to –0.006), and the odds of falling increased by 27% (odds ratio = 1.27, 95% CI = 1.12 to 1.43). Some specific pain sites (extremity pain, widespread pain, and pelvis/groin pain) were associated with greater long-term disability.ConclusionsMultisite pain is common among older adults with persistent back pain. Number of pain sites was associated with all outcomes; individual pain sites were less consistently associated with outcomes.

Download Full-text