All-cause mortality dropped among dementia patients eligible for the shingles vaccine compared with adults who missed eligibility by as little as one week, according to a recent study.
Investigators from Stanford University reporting in Cell assessed the impact of the United Kingdom’s herpes zoster vaccination program on cognitive and mortality outcomes using a natural experiment created by the program’s date-of-birth rule. Because individuals born on or after September 2, 1933, were eligible and those born just a week earlier were not—and remained ineligible for life—the cutoff functioned as a quasi-randomized assignment to vaccine access.
The analysis used anonymized electronic health records from the SAIL Databank and included two cohorts of individuals who were living in Wales as of September 1st, 2013 to capture the full dementia disease course. The first cohort, 282,557 adults without cognitive impairment at baseline, was used to examine whether vaccine eligibility altered the onset or progression of early cognitive decline. The second cohort, 14,350 adults already living with dementia, allowed investigators to assess whether eligibility influenced dementia-related or all-cause mortality. Both groups had comorbidity burdens; for example, prior stroke ranged from 7% in the first cohort to about 18% in the second. Chronic obstructive pulmonary disease was noted at 12% and 14%, respectively. Preventive-care use remained over 60% across both cohorts.
The investigators applied a regression discontinuity design based on the September 2, 1933, birthday, threshold, which produced a sharp 46% increase in vaccine uptake. By restricting analyses to adults born within roughly 95 weeks of the cutoff, the researchers formed treatment and control groups that differed only by a 1-week birthdate yet experienced lifelong differences in vaccine eligibility. Intention-to-treat and complier average causal effects were estimated using fuzzy regression discontinuity, with eligibility serving as the instrument for vaccination.
Eligibility and vaccination affected the two cohorts differently. In adults without cognitive impairment, eligibility reduced new mild cognitive impairment diagnoses by about 1 to 3 percentage points and produced similar reductions in new dementia diagnoses, with consistently larger effects among women. Eligibility also reduced the likelihood of progressing from mild cognitive impairment to dementia once impairment developed.
In adults living with dementia at baseline, eligibility was associated with an approximately 8-percentage-point reduction in dementia-related deaths over 9 years. All-cause mortality also declined in this cohort, again with larger effects in women. Researchers found mortality benefit did not extend to other leading causes of death, and eligibility did not alter uptake of other preventive services, including influenza and pneumococcal vaccination, statin use, or antihypertensive therapy.
Exploratory analyses indicated that reductions in dementia incidence were greatest for mixed dementia compared with Alzheimer or vascular dementia. Additional analyses stratified by dementia severity suggested larger absolute reductions in dementia deaths among adults with more advanced disease. Investigators found no abrupt differences in comorbidities or preventive-care histories at the cutoff, and birth-season difference-in-differences analyses yielded similar findings.
“We came into this without any expectations that we would see strong effects for dementia,” stated study corresponding author, Pascal Geldsetzer, MD, PhD of Division of Primary Care and Population Health, Department of Medicine, Stanford University, Stanford, California in conversation with Stanford Medicine’s 90 Seconds with Lisa Kim.
“We were aware of this budding literature around viruses that preferentially target your nervous system and them potentially being implicated in dementia, but we definitely did not expect such strong protective signals in our data.”
With the surprise of these findings for the investigators and the need to convince the medical community of its importance, the investigators saw the need for further investigation with a clinical trial. Dr. Geldsetzer is spearheading funding efforts from private and philanthropic foundations to definitively test the effectiveness of the shingles vaccine in prevention or delay of dementia. If there is any interest in helping fund this study he can be reached by email (pgeldsetzer@stanford.edu).
The authors reported no competing financial interests and noted that the study was supported by institutional and philanthropic funding and conducted using anonymized data from the SAIL Databank.
Source: Cell
