Preclinical Alzheimer's disease and longitudinal driving decline

Abstract

IntroductionLinks between preclinical Alzheimer's 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.MethodsOne hundred four OAs (65+ years) with normal cognition took part in biomarker measurements, a road test, clinical and psychometric batteries, and self-reported their driving habits.ResultsHigher values of cerebrospinal fluid (CSF) tau/Aβ42 and phosphorylated tau (ptau181)/Aβ42 ratios, but not uptake on Pittsburgh compound B amyloid imaging (P = .12), predicted time to a rating of marginal or fail on the driving test using Cox proportional hazards models. Hazards ratios (95% confidence interval) were 5.75 (1.70–19.53), P = .005 for CSF tau/Aβ42; 6.19 (1.75–21.88), and P = .005 for CSF ptau181/Aβ42.DiscussionPreclinical AD predicted time to receiving a marginal or fail rating on an on-road driving test. Driving performance shows promise as a functional outcome in AD prevention trials.

Neuropsychiatric Symptoms and Alzheimer’s Disease Biomarkers Predict Driving Decline: Brief Report

“…Driving problems arise earlier for participants with preclinical AD [3]. Symptomatic AD (CDR >0) is associated with much faster decline on the NPI-Q than cognitive normality (CDR 0) [7].…”

“…In our sample of cognitively normal older adults, presence of neuropsychiatric symptoms interacted with CSF biomarkers to predict a much faster time to receiving a marginal/fail rating on a road test. While preclinical AD alone predicted a faster time to receiving a marginal/fail rating [3], the presence of NPS increases these problems compared to those without preclinical AD or NPS.…”

“…Participants were required to be cognitively normal (Clinical Dementia Rating = 0 [CDR]) [10], English-speaking, aged 65 years or older, have a valid driver's license, and driving at least once a week. At baseline evaluation, participants underwent biomarker testing, as well as clinical and psychometric assessments, followed by a standardized performance-based road test [3, 4]. At annual follow-ups, participants completed clinical and psychometric assessments and the road test.…”

“…Similar to our previous work [3, 4], we compared the lowest tertile to the other two tertiles for Aβ 42 ; for remaining biomarker values, the highest tertile was compared to the lower two tertiles in our analyses. Compared to normative scores, baseline scores on all subscales of the POMS-SF, GDS, and NPI-Q indicated little to no disturbance as self-reported by participants or collateral source.…”

“…Early identification of these changes prior to symptomatic AD can help to understand the resulting impact on complex activities and functional outcomes like driving. Recent work has shown that cerebrospinal fluid (CSF) and imaging biomarkers predict driving problems and longitudinal driving decline among cognitively normal older adults [3, 4]. Institutions like the National Institute on Aging and Alzheimer's Association recommend research into neurobehavioral outcomes like mood disorders to link the pathological changes to emerging AD symptoms in order to determine the impact on functional decline prior to full symptom onset [5].…”