The effect of college degree attainment on neurodegenerative symptoms in genetically at-risk women

Hong, Jinkuk; Dembo, Robert S.; DaWalt, Leann Smith; Brilliant, Murray H.; Berry‐Kravis, Elizabeth; Mailick, Marsha R.

doi:10.1016/j.ssmph.2022.101262

Cited by 4 publications

(5 citation statements)

References 79 publications

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“…A recent study documented CGG repeat count and stress that independently contributed to executive dysfunction in female FMR1 premutation carriers ( 23 ). As in our study, a higher level of education was emphasized as a “protective factor” ( 24 ).…”

Section: Discussionsupporting

confidence: 60%

An escalating continuum of learning and attention difficulties from premutation to full mutation in female carriers of FMR1 expansion

Gabis

Shaham

Attia³

et al. 2023

Front. Neurol.

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ObjectiveCarriers of Fragile X premutation may have associated medical comorbidities, such as Fragile X-associated tremor and ataxia (FXTAS) and Fragile X-associated premature ovarian insufficiency (FXPOI). We examined the Fragile X premutation effect on cognition, and we assumed that there is a direct correlation between the continuous spectrum of specific learning and attention deficits to the number of CGG repeats on the FMR1 gene.MethodsA total of 108 women were referred to our center due to a related Fragile X syndrome (FXS) patient, 79 women carried a premutation of 56–199 repeats, and 19 women carried a full mutation of more than 200 CGG repeats on FMR1 gene. Genetic results of CGG repeats, demographic information, structured questionnaires for ADHD, learning disabilities of language and mathematics, and independence level were analyzed in women carrying the FMR1 premutation and compared to the group carrying the full mutation. Women with FXS and FXTAS were excluded.ResultsWhen analyzed as a continuum, there was a significant increase in the following complaints which were associated with a higher number of repeats: specific daily function skills such as driving a car, writing checks, disorientation in directions, and also specific learning difficulties such as spelling and math difficulties. Additionally, when tested as a categorical independent variable, we observe that women with the full mutation were more likely to have ADHD or other learning disability diagnoses in the past than during premutation (<200 CGG repetitions).ConclusionSpecific learning and attention difficulties and resulting daily function difficulties correlate with an increased number of CGG repeats and are more likely to be associated as a common feature of premutation and full mutation in a female premutation carrier. Despite evidence of learning and attention difficulties, it is encouraging that most female carriers of the premutation and full mutation function well in most areas. Nevertheless, they face significant difficulties in specific areas of functioning such as driving, and confusion in times and schedules. Those daily function skills are mostly impacted by dyscalculia, right and left disorientation, and attention difficulties. This may aid to design specific interventions to address specific learning deficits in order to improve daily function skills and quality of life.

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Section: Discussionsupporting

confidence: 60%

An escalating continuum of learning and attention difficulties from premutation to full mutation in female carriers of FMR1 expansion

Gabis

Shaham

Attia³

et al. 2023

Front. Neurol.

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“…Furthermore, symptoms manifested by those who did not attain a college degree worsened over the 9-year study period at a significantly faster rate than the college graduates. These results were published in Hong et al (2022) [337]. Mailick further reported that, for women in the general population (i.e., not a clinical sample), years of postsecondary education interacted with the number of CGG repeats to predict later-life mortality.…”

Section: Fxtas Clinical and Protective Mechanismsmentioning

confidence: 90%

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Tassone,

Protic,

Allen

et al. 2023

Cells

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The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5’ untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

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“…Consistent with much past research conducted on the general population, in the present study the main effect of higher education was found to be associated with a lower risk of mortality, before the intervening factors were introduced. This positive effect of higher education has been observed in a number of studies of FMR1 premutation carriers, where higher education (as a main effect) has been associated with reduced risk of health and cognitive symptoms [30][31][32][33][34]107,108].…”

Section: Discussionmentioning

confidence: 56%

“…The Kaplan-Meier survival functions of three subgroups-25 or fewer CGGs, 26-40 CGGs, and 41-84 CGGs-are similar to the adjusted functions shown in Figure 3. In Figure 4, the survival of women with expanded numbers of CGG repeats (Figure 4c) is substantially greater than those with normal-range repeats (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), as well as those with 25 or fewer repeats.…”

Section: Cox Proportional Hazard Models Predicting Mortalitymentioning

confidence: 94%

“…With respect to the FMR1 gene, only a few prior studies have reported data on the beneficial effects of higher education with respect to health. In these studies, findings indicate that those with higher levels of education have better motor, cognitive [30], and executive functioning [31], a lower prevalence of FXTAS [32,33], and fewer related neurological symptoms [34]. All of these studies were based on clinically-ascertained samples, with no prior studies examining whether the benefits of higher education vary by CGG repeat length in a general population sample.…”

Section: Effects Of Higher Education On Mortalitymentioning

confidence: 99%

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Mortality in Women across the FMR1 CGG Repeat Range: The Neuroprotective Effect of Higher Education

Hong,

Dembo,

DaWalt

et al. 2023

Cells

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Higher education has been shown to have neuroprotective effects, reducing the risk of Alzheimer’s and Parkinson’s diseases, slowing the rate of age-related cognitive decline, and is associated with lower rates of early mortality. In the present study, the association between higher education, fragile X messenger ribonucleoprotein 1 (FMR1) cytosine–guanine–guanine (CGG) repeat number, and mortality before life expectancy was investigated in a population cohort of women born in 1939. The findings revealed a significant interaction between years of higher education and CGG repeat number. Counter to the study’s hypothesis, the effects of higher education became more pronounced as the number of CGG repeats increased. There was no effect of years of higher education on early mortality for women who had 25 repeats, while each year of higher education decreased the hazard of early mortality by 8% for women who had 30 repeats. For women with 41 repeats, the hazard was decreased by 14% for each additional year of higher education. The interaction remained significant after controlling for IQ and family socioeconomic status (SES) measured during high school, as well as factors measured during adulthood (family, psychosocial, health, and financial factors). The results are interpreted in the context of differential sensitivity to the environment, a conceptualization that posits that some people are more reactive to both negative and positive environmental conditions. Expansions in CGG repeats have been shown in previous FMR1 research to manifest such a differential sensitivity pattern.

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The effect of college degree attainment on neurodegenerative symptoms in genetically at-risk women

Cited by 4 publications

References 79 publications

An escalating continuum of learning and attention difficulties from premutation to full mutation in female carriers of FMR1 expansion

An escalating continuum of learning and attention difficulties from premutation to full mutation in female carriers of FMR1 expansion

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation

Mortality in Women across the FMR1 CGG Repeat Range: The Neuroprotective Effect of Higher Education

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