Jet MJ Vonk’s research while affiliated with University of California, San Francisco and other places

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Publications (8)


Cognitive Reserve in Individuals with Frontotemporal Dementia: A Systematic Review
  • Article
  • Full-text available

January 2025

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19 Reads

Lauren A Grebe

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Jet MJ Vonk

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Elizabeth Galletta

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Mira Goral

Background In comparison to robust evidence for cognitive reserve (CR) in individuals with Alzheimer’s‐related dementia, the literature on CR in frontotemporal dementia (FTD) is still emerging. A clear consensus on the relationship among CR, brain status, and clinical performance has not been reached. The aims of this systematic review were to: 1) document the FTD disorders represented in this literature and their diagnosis descriptions, 2) classify the sociobehavioral proxies of CR used, 3) identify the tools used to measure disease severity, clinical performance, and brain status, and 4) examine the relationship between CR and brain status in individuals with FTD. Method Systematic review of the literature was conducted using a comprehensive range of relevant search terms in Medline, PsychINFO, PubMed, and Web of Science. Eligibility criteria were for studies to: include at least one proxy of CR and one brain status measure for individuals with FTD, be published in a peer‐reviewed journal, and be published in English. The Newcastle‐Ottawa Quality Assessment Scale was used to assess the quality of the included studies and risk of bias based on three domains: participant selection, comparability of included groups, and quality of outcome measures. Result A total of 220 titles and abstracts were screened, with 13 studies meeting inclusion criteria. Together, these studies report 1,423 participants diagnosed with FTD. Across studies, three proxies of CR were incorporated as either continuous or categorical variables: education, occupation, and leisure. Seven tools were used to measure disease severity and three neuroimaging tools were used to measure brain status. All included studies reported significant associations between a CR proxy and a brain measure. However, only partial support was demonstrated for the CR theory in individuals with FTD when education, occupation, and leisure involvement were analyzed in relation to disease severity. Conclusion The variable results among studies could be related to the different tools used to measure CR, the numerous brain status measures incoporated, and the different ways researchers determine disease severity. Recommendations for future studies include incorporating longitudinal designs, using in‐depth neuropsychological testing, improving measurement of disease duration, and transparant reporting of statistical output.

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Effect of early‐ and mid‐life cognitive enrichment on Alzheimer’s disease pathology and late‐life cognition

December 2023

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11 Reads

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Jet MJ Vonk

Background Cognitive reserve and brain maintenance may explain individual differences in trajectories of cognitive and brain aging due to various life exposures (e.g., education, cognitive enrichment). Cognitive reserve refers to the advantages that life exposures exert on cognitive abilities despite brain aging or disease; brain maintenance refers to the protective effects of life exposures on the brain itself (e.g., reduced rate of neuropathology accumulation). Previous findings showed that early‐life cognitive enrichment (ELCE) was associated with slower cognitive decline, which was partially mediated through global Alzheimer’s disease pathology. Building on this work, this study investigated mediation by β‐amyloid and tau pathology (reflecting brain maintenance) as well as moderation by early‐ and mid‐life cognitive enrichment (ELCE, MLCE; reflecting cognitive reserve) on cognitive functioning at last visit proximate to death. Method There were 1015 community‐based participants (M baseline age = 82.57±6.35) from the Rush Memory and Aging Project (MAP) and Minority Aging Research Study (MARS) cohorts, who completed annual cognitive and clinical assessments. ELCE and MLCE composite measures were derived from z‐scored self‐reported indicators obtained at baseline (Table 1). Summary measures of β‐amyloid and tau burden were derived from immunohistochemistry at autopsy. Late‐life cognition was measured using a global composite of 19 z‐scored neuropsychological tests obtained at last visit. To test for cognitive reserve, separate linear regression models examined whether ELCE and MLCE moderated relations between β‐amyloid or tau and cognition, adjusted for age at death and sex. To test for brain maintenance, a series of mediation analyses examined whether β‐amyloid and/or tau burden mediated the relationship of ELCE and MLCE with cognition. Result ELCE (p = .005) and MLCE (p = .005) moderated the relationship between tau—but not β‐amyloid—and late‐life cognition proximate to death (Figure 1). Mediation analyses revealed an indirect effect of β‐amyloid—but not tau—on the relation between ELCE (B = 0.058, p = .004) and MLCE (B = 0.040, p = .03) and late‐life cognition (Figure 2). Conclusion ELCE and MLCE improve late‐life cognition partially through reducing β‐amyloid, but not tau, accumulation (i.e., brain maintenance). In contrast, ELCE and MLCE are protective against late‐life cognitive impairment in the presence of tau pathology (i.e., cognitive reserve), but not β‐amyloid.


LANGUAGE-BASED DISCRIMINATION RELATES TO MEMORY COMPLAINTS AMONG LATINX/HISPANIC OLDER ADULTS

December 2022

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35 Reads

Innovation in Aging

Memory Complaints (MCs) are a risk factor for dementia, but research in this area has largely been limited to non-Latinx White adults. Previous studies have shown that Latinx/Hispanic individuals are at higher risk for Alzheimer’s Disease and Related Disorders (ADRD). The mechanisms underlying this disparity in ADRD are multidimensional and can include negative social stressors such as discrimination. Language discrimination can be a source of stress in this population and might be an important contributor to MCs. We examined if MCs varies as a function of language-based discrimination in a total of 495 Latinx/Hispanic older adults without dementia from the community-based Washington Heights Inwood Columbia Aging Project. Language-based discrimination was measured with a dichotomous item that inquired if individuals had been discriminated against because they do not speak English well (yes or no). A linear regression was conducted to examine the cross-sectional association between language-based discrimination and MCs adjusted for age, education, sex/gender, socioeconomic status (income), and depressive symptoms. The experience of language discrimination was independently associated with MCs (B= 0.83, 95% CI=0.13, 1.54, SE= 0.36, p= .021). Results demonstrate a relationship between negative stressors and the expression of MCs. Future studies should comprehensively examine other discriminatory stressors which may also impact the expression of MCs and the risk for progression to ADRD. Identifying language-based and other discriminatory stressors that negatively affect Latinx/Hispanic communities will allow us to develop models that aim to assess and prevent discrimination, as a protective mechanism for the development of MCs and ADRDs.


Figure 2. Longitudinal relationship between memory (z-score), low-grade carotid stenosis, and no stenosis. Age of patients at each visit was chosen as the time variable. The shaded grey area represents the 95% confidence interval. Results adjusted for sex, education level, large infarcts on MRI, lacunes on MRI, hypertension, diabetes mellitus, body mass index, smoking pack years, alcohol use and practice effect.
Output of the linear mixed-effects models with age of patients at each visit as the time variable, neuroimaging outcomes as dependent variables and low-grade carotid stenosis as independent variable.
Low-grade carotid artery stenosis is associated with progression of brain atrophy and cognitive decline. The SMART-MR study

October 2022

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73 Reads

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9 Citations

Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism

Asymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease - Magnetic Resonance (SMART-MR) study without a history of cerebrovascular disease. LGCS was defined as 1-49% stenosis on baseline carotid ultrasound, whereas no LGCS (reference category) was defined as absence of carotid plaque. Brain and white matter hyperintensity (WMH) volumes and cognitive function were measured at baseline and after 4 (n = 480) and 12 years (n = 222) of follow-up. Using linear mixed-effects models, we investigated associations of LGCS with progression of brain atrophy, WMH, and cognitive decline. LGCS was associated with greater progression of global brain atrophy (estimate -0.03; 95%CI, -0.06 to -0.01; p = 0.002), and a greater decline in executive functioning (estimate -0.02; 95%CI, -0.031 to -0.01; p < 0.001) and memory (estimate -0.012; 95%CI, -0.02 to -0.001; p = 0.032), independent of demographics, cardiovascular risk factors, and incident brain infarcts on MRI. No association was observed between LGCS and progression of WMH. Our results indicate that LGCS may represent an early marker of greater future brain atrophy and cognitive decline.


When verbal fluency inverts: Temporality of semantic impairment in preclinical Alzheimer’s disease

December 2021

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8 Reads

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2 Citations

Background Worse semantic than letter fluency performance is a clinical marker of Alzheimer’s disease (AD), but the longitudinal course of performance on these tasks in pre‐dementia stages remains undefined. This study investigated how many years before clinical AD the performance on the two verbal fluency tasks starts to diverge, and if this process develops similarly across race/ethnicity groups. Method To estimate the trajectories and inflection point of verbal fluency performance in years prior to AD diagnosis, we performed piece‐wise linear mixed effects models in a diverse sample of 569 individuals (mean age = 78.5) from a community‐based cohort who were cognitively normal at baseline but developed dementia across 10 years of follow‐up (up to 5 visits). Performance was standardized on 569 age, sex/gender, education, and race/ethnicity matched controls who remained cognitively healthy during follow‐up (i.e., robust norms approach). Models were adjusted for recruitment wave and demographic factors. Result AIC model comparison of spline‐fit revealed that prior to AD diagnosis, performance on both fluency tasks started to decline more rapidly 3.6 years before diagnosis (slope within later timeframe: semantic: B=‐1.34 [‐1.52, ‐1.16], p<.001; letter: B=‐.56 [‐.70, ‐.42], p<.001). Point‐in‐time performance on semantic fluency became worse than letter fluency as of approximately 2.8 years before AD diagnosis due to the disproportionally fast decline of semantic fluency. Stratified models showed that the inflection point for Whites was earlier than for Blacks and Hispanics, but that the rate of decline and flip in performance between the two tasks was similar across race/ethnicity. Conclusion These results show how the conventional clinical index of worse semantic than letter fluency develops over time in the years before AD diagnosis. This study highlights the importance of serial neuropsychological assessments in detecting high‐risk individuals by showing that the differential rate of decline in semantic versus letter fluency is a sensitive preclinical AD‐marker, equivalent across race/ethnicity.


Racial differences in cognitive resilience to parental history of AD and cognitive impairment: The Offspring study

December 2021

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14 Reads

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3 Citations

Background The effect of family history on risk of developing late‐onset AD differs across race/ethnicity; however, the mechanisms underlying AD risk or resilience through heritability of genetic, environmental, and health factors are not well understood. Few large‐scale cohort studies have prospectively‐collected data of both parental and offspring generations and most intergenerational AD research is performed among volunteer‐based, well‐educated, White parents and offspring. We examined whether the association of midlife cognitive function with parental dementia status differs across race and ethnicity. Method Cognitive function was assessed in non‐Latinx White (n=66), non‐Latinx Black (n=181), Latinx English speaking (n=224), and Latinx Spanish speaking (n=362) people age 27 to 91 (mean age=56.5). Participants were offspring of participants in WHICAP, a community‐based sample of Medicare‐eligible residents of Washington Heights aged 65 and older. Of the 833 offspring, 610 families were represented, of which 176 (29%) parents were demented. We examined the association of parental dementia status on offspring measures of memory, attention, working memory, fluency, and processing speed, after adjusting for offspring age, sex/gender, parental education, and family relatedness, and tested for interactions between parental dementia status and racial/ethnic group. Next, we used multiple‐group analyses determined whether parental baseline memory performance predicted offspring cognitive test scores, adjusting for covariates. Result Offspring of WHICAP parents with dementia obtained lower scores on measures of memory, working memory, and attention, but processing speed and language were not affected by parental dementia status. Overall, offspring whose parents had poor memory had lower cognitive function across multiple domains (Figure 1); however, parental memory had a stronger impact on offspring memory, working memory, and fluency in non‐Latinx White and English speaking Latinx participants, compared with non‐Latinx Black and Spanish speaking Latinx participants. Conclusion This intergenerational study demonstrated that in middle age, offspring of parents with dementia have poorer cognitive function than offspring of parents without dementia, independent of parental SES; however, the strength of this relationship differed by race, ethnicity, and language. Results suggest that social and biological variables that confer familial risk and resilience may differ based on contextual factors that are patterned by racial and linguistic background.


Temporal ordering of subjective cognitive decline and depressive symptoms in a multiracial community cohort

December 2021

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12 Reads

Background Subjective Cognitive Decline (SCD), a proposed marker of preclinical Alzheimer’s disease (AD), is commonly associated with depressive symptoms. However, the basis and directionality of this association is unclear. Divergent hypotheses propose that mood changes either cause SCD or represent a psychological reaction to perceived cognitive decline. Alternatively, mood and SCD may both be part of a dementia prodrome. Longitudinal evaluation is critical to understand the temporal ordering of SCD and depressive symptoms. Further, given known differences in the prevalence of depressive symptoms across sex‐ethnoracial groups, it is important to examine temporality across these groups. Methods 3365 (68% women, 75 (SD=6) years old, 10 (SD=5) years educated) participants without dementia at baseline were included in this study. Of these, 1005 were non‐Hispanic Black, 1450 Hispanic and 910 non‐Hispanic White. Depressive symptoms were measured using the Center for Epidemiological Studies Depression scale (CES‐D). SCD was assessed with a 9‐item questionnaire assessing memory difficulties. Separate autoregressive generalized additive mixed effects models (GAMMs) were conducted. Each model included a lagged cross‐symptom variable, an autoregressive same‐symptom variable, and a within‐visit association between CES‐D and SCD. Models additionally included age, time in study, dementia status, education and objective memory performance. Primary coefficients of interest were lagged cross‐symptom effects, estimated across and within sex‐ethnoracial groups. Results Whole‐sample results showed similar coefficients for models of SCD predicting depressive symptoms (b=.021, p=.021) and models of depressive symptoms predicting SCD (b=.045, p=.001; Figure 1). Stratified analyses showed that within Black participants, depressive symptoms preceded SCD (b=.098, p<.001) whilst the opposite pattern was seen in Hispanic participants (b=.025, p=.027). With regard to sex, depressive symptoms preceded SCD in men, particularly white men (b=.141, p=.004). In contrast, SCD preceded depressive symptoms in women, primarily Hispanic women (b=.030, p=.019). Conclusions Results provide evidence for bidirectionality between depressive symptoms and SCD, underscoring the multiple pathways by which these two factors are linked in the course of cognitive aging. However, stratified results reveal nuanced patterns between depressive symptoms and SCD across sex‐ethnoracial groups that may offer clues to the relevance of SCD as a marker of pre‐clinical AD in different populations.


Trends in sex/gender differences across whites, blacks, and Hispanics: Intersections of sex/gender and race/ethnicity in cognitive aging and Alzheimer’s disease trajectories

December 2020

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7 Reads

Background We determined if later birth year is associated with an increased verbal memory advantage for women and examined whether childhood socio‐economic status (CSES) and adult socio‐economic status (ASES) explain secular trends similarly across Whites, Blacks, and Hispanics. Method Participants were 5,258 non‐Hispanic White (White), non‐Hispanic Black (Black), and Hispanic men and women in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were administered neuropsychological tests of memory at 18 to 24 month intervals for up to 25 years. Multiple‐group latent growth curve modeling examined trajectories across birth cohorts (before 1925 vs 1925 and later) within sex/gender by race/ethnicity subgroups after adjusting for immigration status (yes/no). Factor scores for CSES (parental education, occupation, and sibship size) and ASES (educational attainment, income, and occupational status) were examined as potential mediators. Result Overall, people born after 1925 and women had higher initial memory performance than people in the earlier birth cohort and men, respectively. However, the benefit of later birth year was restricted to White men and women and Black women, and there was no benefit among Black men or Hispanic men and women. White and Black women demonstrated a similar memory advantage over White and Black men, respectively. This advantage widened for Black women in the later born cohort, but remained similar for later born White women. Hispanic men and women obtained similar memory scores across birth cohorts. While earlier birth year was associated with more rapid rate of decline across racial/ethnic groups, men and women within each birth cohort declined at the same rate. The influence of birth cohort on memory was fully mediated by CSES for White men and mediated by ASES among White and Black women. Conclusion The verbal memory advantage of women varies across and within birth cohorts and racial/ethnic groups. Later birth year was associated with an increased memory advantage for Black women over Black men. Secular trends were differentially explained by childhood and adult SES for White men and White and Black women.

Citations (3)


... This way, we were able to assess the association between any grade of carotid artery stenosis and CSVD burden score in all atherosclerotic CSVD patients, showing that a higher degree of stenosis is associated with increasing CSVD burden score. This is especially interesting as symptomatic patients should have a lower burden score because only asymptomatic LS are calculated in the overall score [25]. ...

Reference:

Carotid artery stenosis is related to cerebral small vessel disease magnetic resonance imaging burden
Low-grade carotid artery stenosis is associated with progression of brain atrophy and cognitive decline. The SMART-MR study

Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism

... As a complement to core learning and recall tests, Alzheimer's disease (AD) assessments typically include verbal fluency tasks. 1 Participants have 1 min to produce words that begin with a given sound (phonemic fluency) or belong to a given category (semantic fluency). 2 These tasks, especially in the semantic condition, reveal early and preclinical deficits 3 which predict anatomo-functional brain dysfunctions. 4,5 Moreover, they are brief, inexpensive, and massively available, 6 highlighting their potential to reveal scalable AD markers. ...

When verbal fluency inverts: Temporality of semantic impairment in preclinical Alzheimer’s disease
  • Citing Article
  • December 2021

... A second limitation is that the present sample nearly exclusively comprised individuals that identified as white Caucasians. While this may be positive methodologically, as possible confounding variables related to race are limited, many studies have highlighted the importance of including a wider spectrum of ethnicities and backgrounds in AD research (Manly et al., 2021;Morris et al., 2019). As far as we are aware, at least with regards to published works, Rr to date has only been tested primarily in white Caucasian populations e future research should consider examining whether the same patterns observed here would also extend to a more heterogeneous sample. ...

Racial differences in cognitive resilience to parental history of AD and cognitive impairment: The Offspring study
  • Citing Article
  • December 2021