Does Multilingualism Protect Against Alzheimer’s Disease Does Multilingualism Protect Against Alzheimer’s Disease? Findings from the Nun Study EE Hack1, SL Tyas1,2, KP Riley3,4 1 Department of Health studies and Gerontology, University of Waterloo 2 Department of Psychology, University of Waterloo 3 Department of Preventative Medicine, University of Kentucky 4 Sanders-Brown Center on Aging, University of Kentucky

The authors have no conflicts of interest with respect to this investigation

Introduction Interest has been mounting concerning the neuroprotective effects of mental engagement The more one is mentally stimulated, the more cognitive reserve one is hypothesized to build against neuropathology-induced cognitive decline Preliminary evidence suggests that multilingualism may protect against the onset of Alzheimer’s disease (AD) - In the past few years, interest has been mounting concerning the potential neuroprotective consequences of high mental engagement in life According to the cognitive reserve hypothesis, the more one is mentally stimulated during their lives, the more cognitive reserve one is hypothesized to build, or maintain, against neuropathology-induced cognitive decline (for instance, in Alzheimer’s disease, which I will refer to as AD) Preliminary evidence suggests that multilingualism, or the ability to fluently speak more than one language, may protect against the onset of AD

Aim To examine the association between multilingualism and AD development The aim of this investigation was to examine the association between multilingualism and the development of AD This study was warranted since past investigations have focused on samples made entirely of AD cases

Methods Sample: The Nun Study 678 members of the School Sisters of Notre Dame Aged 75-102 at baseline assessment 12 waves of cognitive assessment Brain donation at death Sample was restricted to include only participants with complete data on variables and covariates of interest This study used the Nun Study population, which is comprised of 678 members of the School Sisters of Notre Dame These participants were aged 75 and above at their first cognitive assessment 12 waves of follow-up cognitive assessment were conducted, and all participants consented to post-mortem brain donation which is a large strength, as a definitive diagnosis of AD requires both clinical dementia information and data concerning AD neuropathology This population is unique, as all participants were similar across several common confounding variables, such as adult SES, lifestyle habits such as smoking and alcohol use, marital and reproductive status, diet, medical care access, and social supports. Samples were restricted to only participants meeting the criteria for the outcomes of interest (will be outlined in following slides)

Methods 3 AD outcomes considered Comparison group for dementia Clinical dementia AD-CERAD: Dementia + AD pathology (CERAD) AD-NIA: Dementia + AD pathology (NIA-RI) Comparison group for dementia No evidence of clinical dementia Comparison group for AD groups No evidence of clinical dementia or AD pathology Multilingualism Defined as speaking two or more languages fluently Measured via self-report This study considered three separate outcomes when determining criteria for AD cases: clinical dementia, which is the AD outcome that all past investigations have examined (done in the interest of comparison to past evidence) clinical dementia and presence of definite/probable AD neuropathology, as diagnosed using the CERAD (Consortium to establish a registry for Alzheimer’s disease) criterion clinical dementia and presence of high/intermediate likelihood AD neuropathology, as diagnosed using the NIA-RI (National Institute of Aging – Reagan Institute) criterion the comparison group for the outcome of dementia consisted of participants with no evidence of clinical dementia the comparison group for both of the AD outcomes consisted of participants with no evidence of dementia or AD pathology Multilingualism was defined as speaking more than one language fluently, and this was assessed by self-report questionnaire 507 participants provided information concerning the exposure

Analysis Descriptive analyses Logistic Regression models Adjusted for age at death, education, occupation, immigrant status, and presence of ApoE*E4 allele Descriptive analyses were conducted for all of the study samples Logistic regression models were also analysed; these were adjusted for: age at death education occupation immigrant status and presence of one or more Apolipoprotein E E4 alleles (referred to as ApoE E4 alleles), which is a known genetic risk factor for sporadic AD there was no need to adjust for gender, as all participants were female

Results – Logistic regression models Multilingualism was not significantly associated with any of the three outcomes Clinical dementia: OR = 1.19 (0.74, 1.90) AD-CERAD : OR = 1.40 (0.57, 3.41) AD-NIA: OR = 0.93 (0.45, 1.91) ApoE*E4 allele and older age at death were significantly associated with increased odds of AD The adjusted logistic regression analyses yielded similar findings; multilingualism was not significantly associated with any of the three AD outcomes The possession of at least one ApoE E4 allele and increased age at death remained significantly associated with all outcomes of AD

Conclusion Multilingualism was not significantly associated with any outcome of interest Future studies should further examine whether other relationships exist between multilingualism and AD delay in AD onset severity of AD manifestation A developing research area Lack in variety of study designs Account for genetic factors or other unique covariates Multilingualism was not significantly associated with dementia or AD - Future studies of multilingualism should further examine whether there is a relationship between multilingualism and a delay in AD onset or the severity of AD manifestation This research area is still developing; new insights stand to be gained by investigations using a broader variety of designs and accounting for genetic factors or other unique covariates

Acknowledgements School Sisters of Notre Dame religious congregation Funding for the Nun Study at the University of Kentucky: NIA 5R01AG09862, K04AG00553, P50AG05144; and the Kleberg Foundation University of Minnesota, home of the Nun Study

Thank-you!

Results – descriptive analyses Clinical dementia N=408; 48.5% with AD Multilingual: 73.7% cases vs. 70.9% controls AD -CERAD N=171; 67.8% with AD Multilingual: 75.9% cases vs.72.7% controls AD-NIA N=197; 53.2% with AD Multilingual: 68.6% cases vs. 71.7% controls only characteristics significantly associated with AD outcomes were: increased age of death and presence of at least one ApoE E4 allele