Elizabeth K. Vernon

Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels.

OBJECTIVES To evaluate whether cerebrospinal fluid (CSF) and PET Pittsburgh Compound B (PiB) biomarkers of underlying Alzheimer disease (AD) pathology (β-amyloid42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, ptau181/Aβ42 and mean cortical binding potential [MCBP] for PET-PiB) predict changes in mood in cognitively normal older adults. SETTING Knight Alzheimers Disease Research Center (ADRC) at Washington University (WU). PARTICIPANTS Participants, 65 years of age or older, were enrolled from longitudinal studies at the WU Knight ADRC. MEASUREMENTS CSF, PET-PiB biomarkers, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Profile of Mood States-Short Form (POMS-SF), the Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS Data from 118 participants at baseline and 66 participants at one-year follow-up were analyzed. CSF and PET biomarkers were not associated cross-sectionally with any mood disturbances at baseline (p > 0.05). Changes in mood as indicated by the total mood disturbance score on the POMS-SF, selected POMS-SF subscales, GDS, and NPI-Q scores from baseline to one-year follow-up were associated with (p < 0.05) CSF and PET-PiB biomarkers. There was no statistically significant decline in cognitive functioning. CONCLUSIONS Generally, higher values of CSF and PET-PiB biomarkers are associated with more changes in mood in cognitively normal older adults. Further work is needed to understand the temporal development of mood changes over several years during the phase of preclinical AD. Evaluating mood as a noncognitive outcome may provide further insight into the development of preclinical AD in cognitively normal older adults.

Amyloid Imaging, Cerebrospinal Fluid Biomarkers Predict Driving Performance Among Cognitively Normal Individuals.

Postmortem brain studies of older drivers killed in car accidents indicate that many had Alzheimer disease (AD) neuropathologic changes. We examined whether AD biomarkers are related to driving performance among cognitively normal older adults. Individuals with normal cognition, aged 65+ years, and driving at least once per week, were recruited. Participants (N=129) took part in clinical assessments, a driving test, and positron emission tomography imaging with Pittsburgh compound B (PIB) and/or cerebrospinal fluid (CSF) collection. General linear models tested whether the number of driving errors differed as a function of each of the biomarker variables (mean cortical binding potential for PIB, and CSF A&bgr;42, tau, ptau181, tau/A&bgr;42, ptau181/A&bgr;42). Higher ratios of CSF tau/A&bgr;42, ptau181/A&bgr;42, and PIB mean cortical binding potential, were associated with more driving errors (P<0.05). Preclinical AD may have subtle cognitive and functional effects, which alone may go unnoticed. However, when combined, these changes may impact complex behaviors such as driving.

Preclinical Alzheimer's disease and longitudinal driving decline

Links between preclinical Alzheimers disease (AD) and driving difficulty onset would support the use of driving performance as an outcome in primary and secondary prevention trials among older adults (OAs). We examined whether AD biomarkers predicted the onset of driving difficulties among OAs.

Development and interval testing of a naturalistic driving methodology to evaluate driving behavior in clinical research.

Background: The number of older adults in the United States will double by 2056. Additionally, the number of licensed drivers will increase along with extended driving-life expectancy. Motor vehicle crashes are a leading cause of injury and death in older adults. Alzheimer’s disease (AD) also negatively impacts driving ability and increases crash risk. Conventional methods to evaluate driving ability are limited in predicting decline among older adults. Innovations in GPS hardware and software can monitor driving behavior in the actual environments people drive in. Commercial off-the-shelf (COTS) devices are affordable, easy to install and capture large volumes of data in real-time. However, adapting these methodologies for research can be challenging. This study sought to adapt a COTS device and determine an interval that produced accurate data on the actual route driven for use in future studies involving older adults with and without AD. Methods: Three subjects drove a single course in different vehicles at different intervals (30, 60 and 120 seconds), at different times of day, morning (9:00-11:59AM), afternoon (2:00-5:00PM) and night (7:00-10pm). The nine datasets were examined to determine the optimal collection interval. Results: Compared to the 120-second and 60-second intervals, the 30-second interval was optimal in capturing the actual route driven along with the lowest number of incorrect paths and affordability weighing considerations for data storage and curation. Discussion: Use of COTS devices offers minimal installation efforts, unobtrusive monitoring and discreet data extraction. However, these devices require strict protocols and controlled testing for adoption into research paradigms. After reliability and validity testing, these devices may provide valuable insight into daily driving behaviors and intraindividual change over time for populations of older adults with and without AD. Data can be aggregated over time to look at changes or adverse events and ascertain if decline in performance is occurring.

USE OF SLEEP MEDICATIONS IS ASSOCIATED WITH POORER COGNITION IN OLDER MALE ADULTS: THE CACHE COUNTY STUDY (USA)

mmHg] than those with MCI [149.0 (23.7) mmHg] and cognitive normal [143.7 (22.6) mmHg] (P < 0.0001). After adjusted for confounders, the likelihood risk of having dementia was positively associated with hypertension (OR1⁄42.75, 95%CI: 1.23, 6.13), higher systolic blood pressure (OR1⁄41.14 per 10mmHg, 95%CI: 1.03, 1.26), higher diastolic blood pressure (OR1⁄41.29 per 10mmHg, 95%CI: 1.07, 1.56), stage 2 hypertension (OR1⁄42.23, 95%CI: 1.12, 4.42), or stage 3 hypertension (OR1⁄42.40, 95%CI: (1.09, 5.26)]. Conclusions:Our results suggest that high blood pressure may be a potential risk factor for dementia. Blood pressure management for the elderly is important for maintaining cognitive vitality.

REPRODUCTIVE WINDOW AND MODERATING FACTORS ASSOCIATED WITH RISK FOR ALZHEIMER’S DISEASE: THE CACHE COUNTY STUDY

battery administered close to examination cycle 7. We used a series of linear regression models to relate the cumulative MIND diet score to performance across each cognitive outcome, adjusting for age, sex, calorie intake, education, the time interval between exam7 and cognitive assessment, BMI, physical activity, diabetes, smoking, depression, CVD, hypertension and total cholesterol to HDL ratio. Results: Every unit increase in the MIND diet score was associated with superior global cognition [b6SE (p): 0.0460.01(<0.01)], episodic memory [0.1260.05(0.01)], processing speed [0.0160.004(<0.01)], abstract reasoning [0.116 0.04(0.01)], and visual memory [0.1260.04(<0.01)]. Significant interactions were observed with the APOE genotype. Stratified analyses revealed that MIND diet adherence was associated with superior global cognition [0.0860.02(0.001)], episodic memory [0.4260.11(<0.001)], executive function [0.0260.01(0.04)], and processing speed [0.0360.01(<0.01)] among APOE 34 carriers. Conclusions:Higher adherence to the MIND diet was independently associated with markers of preclinical AD and VBI. Further studies are needed to elucidate whether adopting the MIND diet can alter cognitive trajectories with aging, particularly in APOE 34 carriers.

Attenuation of practice effects on neuropsychological performance is a potential marker of preclinical Alzheimer's disease

(p< .01), visual recall (p1⁄4.03), attention (p1⁄4.02), and set-shifting (p1⁄4.01). Using the Super-Normal group norms, Progressors reached a -1.5 SD decline in logical memory earlier than using the combined group norms. Across a range of SD cutoff scores, diagnostic sensitivity improved to amaximum of 84% true positive, but specificity remained unacceptably low and mostly decreased compared to the combined group norms.Conclusions: Including individuals with preclinical AD in normative samples increases variability and magnifies age effects. However, cognitive cutoff scores, even those derived from exceptionally robust norms, have poor specificity and should not be used to diagnose AD.