Cerebral Palsy and Dementia

Ng,T.K.S., Tagawa, A., Ho, R.C., Larbi, A., Kua, E.H., Mahendran, R., Carollo, J.J., & Heyn, P.C.

Aging (Albany NY), 2021, 13.  https://doi.org/10.18632/aging.202563 [Epub ahead of print]

https://doi.org/10.18632,/aging.202563

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Abstract: Clinically, individuals with cerebral palsy (CP) experience symptoms of accelerated biological aging. Accumulative deficits in both molecular underpinnings and functions in young adults with CP can lead to premature aging, such as heart disease and mild cognitive impairment (MCI). MCI is an intermediate stage between healthy aging and dementia that normally develops at old age. Owing to their intriguingly parallel yet “inverted” disease trajectories, CP might share similar pathology and phenotypes with MCI, conferring increased risk for developing dementia at a much younger age. Thus, we examined this hypothesis by evaluating these two distinct populations (MCI= 55, CP = 72). A total of nine measures (e.g., blood biomarkers, neurocognition, Framingham Heart Study Score (FHSS) were compared between the groups. Compared to MCI, upon controlling for covariates, delta FHSS, brain-derived neurotrophic factor (BDNF) levels, and systolic blood pressure were significantly lower in CP. Intriguingly, high-sensitivity CRP, several metabolic outcomes, and neurocognitive function were similar between the two groups. This study supports a shared biological underpinning and key phenotypes between CP and MCI. Thus, we proposed a double-hit model for the development of premature aging outcomes in CP through shared biomarkers. Future longitudinal follow-up studies are warranted to examine accelerated biological aging.

Smith,K. Peterson, M., Victor,C, & Ryan, J.

Innovations in Aging, 2018 Nov; 2(Suppl 1), 980.

Published online 2018 Nov 16. doi: 10.1093/geroni/igy031.3628

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Abstract: Researchers have previously hypothesized that aging with cerebral palsy (CP) may be associated with an increased risk of developing dementia. However no study has yet formally investigated this proposition while accounting for important morbidities such as intellectual disability (ID) or epilepsy. We used a United Kingdom primary care database as our data source (CPRD Gold). Data for 1,705 adults with CP (age range 18–89) and 5,115 age, sex and general practice matched controls without CP was extracted from the database. Dementia was defined by read codes. We used stratified Cox Proportional Hazards Regression analyses to determine incidence of dementia. In total there were 51 cases of incident dementia over follow-up. There was no significant difference in the risk of developing dementia between people with CP and those without CP (HR 1.40, 95% CI 0.58–3.40). We then repeated our analysis comparing those with CP and either ID or epilepsy with adults without CP. Those with ID co-morbidity had a higher risk of developing dementia than people with no CP (HR 7.11, 95% CI 1.38–36.75) as did those with CP and epilepsy (HR 12.0, 95% CI 1.34–107.36). Results suggest that only those people with CP and ID or epilepsy are more likely to develop dementia. This suggests that the previously speculated link between CP and dementia may be due to other neurologic or intellectual co-morbidities rather than as a direct effect of CP; however, more work is needed to confirm this link and the mechanisms underlying it.

Smith, K.J.,Peterson, M.D.,Victor, C., & Ryan, J.M.

BMJ Open, 2021;11:e042652. doi:10.1136/ bmjopen-2020-042652

Abstract: Determine the risk of incident dementia in adults with cerebral palsy (CP) compared with age, sex and general practice (GP) matched controls. A retrospective cohort study designed was used. The setting was the UK using GPs linked into the Clinical Practice Research Datalink (CPRD). CPRD data were used to identify adults aged 18 or older with a diagnosis of CP. Each adult with CP was matched to three controls who were matched for age, sex and GP. In total, 1703 adults with CP and 5109 matched controls were included in the analysis. The mean baseline age of participants was 33.30 years (SD: 15.48 years) and 46.8% of the sample were female. The primary outcome included a new diagnosis of dementia during the follow-up period (earliest date of 1987 to latest date of 2015).  The results showed that during the follow- up, 72 people were identified with a new diagnosis of dementia. The overall proportion of people with and without CP who developed dementia was similar (CP: n=19, 1.1%; matched controls n=54, 10.0%). The unadjusted HR suggested that people with CP had an increased hazard of being diagnosed with dementia when compared with matched controls (HR 2.69, 95% CI 1.44 to 5.00). This association was attenuated when CP comorbidities (sensory impairment, intellectual disability and epilepsy) were accounted for (HR 1.92, 95% CI 0.92 to 4.02). There was no difference in the proportion of people with CP and matched controls who were diagnosed with dementia during the follow-up. Furthermore, while there was evidence for an increased hazard of dementia among people with CP, the fact that this association was attenuated after controlling for comorbidities indicates that this association may be explained by comorbidities rather than being a direct result of CP. Findings should be interpreted with caution due to the low number of incident cases of dementia.

Mahmoudi, E., Lin, P., Kamdar, N, Gonzales, G., Norcott, A., & Peterson, M.D.Developmental Medicine & Child Neurology, First published 8 September 2021, https://doi/org/10.1111.dmcn.15044

Abstract: To examine the risk of Alzheimer disease and related dementia (ADRD) among adults with cerebral palsy (CP). Using administrative insurance claims data for 2007 to 2017 in the USA, we identified adults (45y or older) with a diagnosis of CP (n=5176). Adults without a diagnosis of CP were included as a typically developing comparison group (n=1 119 131). Using age, sex, ethnicity, other demographic variables, and a set of chronic morbidities, we propensity-matched individuals with and without CP (n=5038). Cox survival models were used to estimate ADRD risk within a 3-year follow up.The unadjusted incidence of ADRD was 9 and 2.4 times higher among cohorts of adults 45 to 64 years (1.8%) and 65 years and older (4.8%) with CP than the respective unmatched individuals without CP (0.2% and 2.0% among 45–64y and 65y or older respectively). Fully adjusted survival models indicated that adults with CP had a greater hazard for ADRD (among 45–64y: unmatched hazard ratio 7.48 [95% confidence interval {CI} 6.05–9.25], matched hazard ratio 4.73 [95% CI 2.72–8.29]; among 65y or older: unmatched hazard ratio 2.21 [95% CI 1.95–2.51], matched hazard ratio 1.73 [1.39–2.15]). Clinical guidelines for early screening of cognitive function among individuals with CP need updating, and preventative and/or therapeutic services should be used to reduce the risk of ADRD.

Smith, S.E., Gannotti, M., Hurvitz, E.A., Jensen, F.E., Krach, L.E., Kruer, M.C., Msall, M.E., Noritz, G., Rajan, D.S., & Aravamuthan, B.R.Annuals of Neurology, 2021, May, 89(5), 860-871.  https://doi.org/10.1002/ana.26040

Abstract: Cerebral palsy (CP) neurologic care and research efforts typically focus on children. However, most people with CP are adults. Adults with CP are at increased risk of new neurologic conditions, such as stroke and myelopathy, that require ongoing neurologic surveillance to distinguish them from baseline motor impairments. Neurologic factors could also contribute to the motor function decline, chronic pain, and chronic fatigue that are commonly experienced by adults with CP. Based on a systematic literature review, we suggest (1) guidelines for neurologic surveillance and neurologist referral and (2) clinical research questions regarding the evolving neurologic risks for adults with CP.

Haak, P., Lenski M., Cooley Hidecker, M.J., Li, M. & Paneth, N.

Developmental Medicine & Child Neurology, 2009, 51(s4), 16-23. First published: 03 September 2009

https://doi.org/10.1111/j.1469-8749.2009.03428.x

Abstract: Cerebral palsy (CP), the most common major disabling motor disorder of childhood, is frequently thought of as a condition that affects only children. Deaths in children with CP, never common, have in recent years become very rare, unless the child is very severely and multiply disabled. Thus, virtually all children assigned the diagnosis of CP will survive into adulthood. Attention to the adult with CP has been sparse, and the evolution of the motor disorder as the individual moves through adolescence, young adulthood, middle age, and old age is not well understood. Nor do we know what happens to other functional domains, such as communication and eating behavior, in adults with CP. Although the brain injury that initially causes CP by definition does not progressively worsen through the lifetime, the effects of CP manifest differently throughout the lifespan. The aging process must inevitably interact with the motor disorder, but we lack systematic, large-scale follow-up studies of children with CP into adulthood and through adulthood with thorough assessments performed over time.  This paper summarizes what is known of the epidemiology of CP throughout the lifespan, with respect to mortality and life expectancy, and what is known of functioning, ability, and quality of life of adults with CP. The authors also describe a framework for future research on CP and aging that is built around the World Health Organization’s International Classification of Functioning, Disability, and Health (ICF) and suggest specific tools and approaches for conducting that research in a sound manner.

Mahmoudi, E.

Archives of Physical Medicine and Rehabilitation, 2021 (Oct), 102(10), E14, DOI:https://doi.org/10.1016/j.apmr.2021.07.431

Abstract: Adults with congenital (cerebral palsy or spina bifida (CP/SB)) or acquired disabilities (spinal cord injury (SCI) or multiple sclerosis (MS)) have higher incidence of age-related health conditions. There is a gap in the literature about the risk of dementia among adults living with these disabilities. This study aimed to examine time to incidence of Alzheimer's disease and related dementia (ADRD) among these disability cohorts.Incidence of ADRD was compared at 4-years. Cox Regression was used to estimate adjusted hazard ratios (aHR) for incident early and late onset ADRD.Using national private payer claims data from 2007-2017, we identified adults (45+) with diagnosis of CP/SB (n=7,226), SCI (n=6,083), and MS (n=6,025). Adults without disability diagnosis were included as controls. Using age, sex, race/ethnicity, cardiometabolic, psychologic, and musculoskeletal chronic conditions, and socioeconomic variables, we propensity score matched persons with and without disabilities.We identified adults (45+) with diagnosis of CP/SB (n=7,226), SCI (n=6,083), and MS (n=6,025). Adults without disability diagnosis were included as controls.The exposure variable was diagnosis with either congenital or acquired disability. Main outcome variable was incident Alzheimer's disease and related dementia. Incidence of early and late onset ADRD were substantially higher among people with disabilities compared to their non-disabled counterparts. Adults with CP, SCI, and MS had higher risk for early [CP/SB: aHR= 3.35 (95% CI: 2.18-5.14); SCI: aHR=1.93 (95% CI:1.06-3.51); and MS: aHR=4.49 (95% CI:2.62-7.69)] and late [CP: aHR=1.68 (95% CI:1.38-2.03); SCI: aHR: 1.77 (95% CI:1.55-2.02); and MS: aHR=1.26 (95% CI:1.04, 1.54)] onset ADRD.  Risk of ADRD was higher among adults with CP/SB, SCI, and MS compared to their matched cohort without disability. Investment in early screening and use of therapeutic or rehabilitative services that may help preserving cognitive function among these patient cohorts is warranted.