New research was presented at AAIC 2020, the virtual Alzheimer’s Association International Conference. The features below highlight some of the studies that emerged from the conference.
Influenza Vaccination & Reduced AD Incidence
With prevention remaining a valuable approach to fighting Alzheimer’s disease (AD), due to the lack of efficacious treatments, researchers sought to statistically test the relationship between influenza vaccination and AD, with the hope of identifying a candidate for AD prevention. Using an EHR dataset of patients an ICD-9 code indicating AD diagnosis, and excluding patients younger than 60, the study team assessed vaccinated and unvaccinated patients. To analyze the effects of frequency of vaccination, they divided the number of vaccinations by the length of time from the first vaccination timestamp to AD onset or the end of the observation. Influenza vaccination significantly decreased AD prevalence in the study population (odds ratio [OR], 0.8309), the frequency of influenza vaccine had a significant impact to inhibit AD onset (OR, 0.8736), and time-to-event analysis showed that receiving the influenza vaccine at an early age led to smaller AD risk when compared with receiving the vaccine at an older age, with a 1 year increase in first vaccination age associated with an increased hazard ratio of 1.0924. “This result provides evidence that influenza vaccination may be a confounding factor in epidemiological studies of risk factors of [AD],” write the study authors
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Phospho-tau217 as a Biomarker for AD
In order to evaluate whether cerebrospinal fluid (CSF) tau phosphorylated at threonine 217 (p-tau217) or plasms p-tau217 are even better biomarkers of Alzheimer’s disease (AD) than p-tau181, study investigators compared CSF p-tau217 and CSF p-tau81 among a cohort of nearly 200 and evaluated plasma p-tau217 and plasma p-tau181 in three cohorts with 1,438 participants. CSF p-tau217 had stronger correlations with the tau-PET tracer, and more accurately identified individuals with abnormal tau-PET scans than CSF P-tau181. CSF P-tau217 correlated better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguished AD dementia from non-AD neurodegenerative disorders. Antemortem plasma P-tau217 differentiated individuals with intermediate-to-high likelihood of AD according to neuropathology from those without AD and performed significantly better than plasma P-tau181. Plasma P-tau217 also differentiated clinical AD dementia from non-AD neurodegenerative diseases significantly better than plasma P-tau181, plasma neurofilament light, and established MRI measures, and similar to CSF P-tau217, CSF P-tau181, CSF Aβ42/40, and tau-PET. Increased plasma P-tau217 was observed already in the pre-symptomatic stages of AD. In PSEN1 mutation carriers, the increase started at age 25, about 20 years prior to estimated onset of mild cognitive impairment. Plasma P-tau217 correlated with cerebral tau tangle densities in subjects with neuritic plaques. It predicted abnormal tau-PET scans significantly better than plasma P-tau181, plasma neurofilament light, CSF P-tau181 and CSF Aβ42/Aβ40, and similar to CSF P-tau217.
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Early-Life Education Quality & Later Dementia Risk
For a study, researchers examined indicators of state-level administrative school quality as predictors of cognitive decline and dementia risk in later life across racial/ethnic groups by sex/gender. Participants included nearly 2,500 men and women who attended elementary school in the US who were followed for up to 21 years. After adjusting for age, childhood socioeconomic status, and state of childhood residence, higher early-life education quality was found to be associated with level and change in language performance across all groups, level of memory performance in black women, and change in memory for non-Hispanic white men and women and black women. Higher education quality was associated with lower dementia risk for non-Hispanic white women and black men and women, but it was not associated with dementia risk for non-Hispanic white men after accounting for covariates. When models included years of education, the influence of school quality on dementia risk, as well as level and change in memory and language performance, was fully attenuated for black men and partially attenuated for non-Hispanic white men and women and black women. “These findings provide evidence that later life brain health is influenced by early-life state educational policies,” write the study authors.
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Too Little or Too Much Sleep Ups AD Risk
With research indicating that sleep disturbances are common and on the rise and increasing awareness of the intricate link between sleep health and brain health, investigators assessed self-reported sleep traits—hours of nighttime sleep, daytime sleepiness, sleep apnea diagnosis, snoring, and napping—among more than 500,000 individuals who were free from Alzheimer’s disease (AD) at baseline and followed for up to 12 years. When compared with those who slept an average of 6-9 hours per night, those who slept more than 9 hours had a higher risk of AD (hazard ratio [HR], 2.05) during a mean follow-up of 6.4 years. Sleep apnea (HR, 2.05) and daytime sleepiness (HR, 1.56) also raised the risk for AD significantly, with both remaining predictive of AD after controlling for sleep duration. However, no associations were observed between snoring and AD risk or between napping and AD risk. Among the 932 participants who developed AD during follow-up, the average time to diagnosis was more than 6 years, a possibly “significant window of time to intervene,” said the lead author of the study.
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Encouraging Results With Plasma Exchange
Plasma exchange treatments have been used for decades to treat various neurologic, immunologic, and metabolic disorders, with treatment including plasmapheresis, or the separation or plasma from blood cells and removal or toxic substances. The albumin in plasma, to which plasma amyloid beta is bound, is replaces with fresh albumin made from the plasma of healthy donors. Researchers hypothesized that by removing albumin together with amyloid beta and replacing it with a newer albumin periodically, they might be able to remove amyloid beta from the cerebrospinal fluid and eventually the brain. To test this hypothesis, they randomized men and women aged 55-85 with probable AD dementia to sham treatment or one of three doses of albumin and intravenous immunoglobulin replacement (equal amounts replaced as removed, half the amount replaced as removed, only albumin replaced). For 6 weeks, participants received weekly sham or conventional plasma exchange treatment of 2.5-3 liters of plasma, followed by 12 months of monthly, low-volume (700-800 mL) plasma exchange or sham treatments. With no clear differences between the three active-treatment groups, the Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale showed a 52% lower decline in change from baseline to 14 months in the plasma exchange-treated group, when compared with the sham group, while the Alzheimer’s Disease Assessment Scale–Cognitive Subscale showed a 66% lower decline.
