Stacy Andersen

Boston University | BU · Department of Medicine, Section of Geriatrics

Background: Discovering patterns of cognitive domains and characterizing how these patterns associate with other risk factors and biomarkers can improve our understanding of the determinants of cognitive aging. Objective: To discover patterns of cognitive domains using neuropsychological test results in Long Life Family Study (LLFS) and characte...

Mosaic chromosomal alterations (mCAs) are structural alterations associated with aging, cancer, cardiovascular disease, infectious diseases, and mortality. The distribution of mCAs in centenarians and individuals with familial longevity is poorly understood. We used MOsaic CHromosomal Alteration (MoChA) to discover mCAs in 2050 centenarians, offspr...

Background: Age-related changes in immune cell composition and functionality are associated with multimorbidity and mortality. However, many centenarians delay the onset of aging-related disease suggesting the presence of elite immunity that remains highly functional at extreme old age. Methods: To identify immune-specific patterns of aging and...

We conducted a genome-wide association study of Digit Symbol Substitution Test scores administered in 4207 family members of the Long Life Family Study (LLFS). Genotype data were imputed to the HRC panel of 64,940 haplotypes resulting in ∼15M genetic variants with a quality score > 0.7. The results were replicated using genetic data imputed to the...

We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The combined data included 2304 EL cases and 5879 controls. The analysis identified a locus in CDKN2B-AS1 (rs6475609, p = 7.13 × 10−8) that almost reached gen...

Cognitive tests that require a spoken response, such as paragraph recall, are rich in cognitive‐related information that is not captured using traditional scoring methods. This study aimed to determine whether linguistic features embedded in spoken responses can differentiate between individuals who are and are not cognitively impaired. We used lin...

Data‐driven approaches are powerful for identifying impaired neurocognitive constructs and aid in characterizing neurocognitive impairment patterns. There is, however, a significant clinical need for time‐efficient diagnostic tools compared to traditional more time‐consuming neuropsychological (NP) assessments. We evaluated how NP errors can compre...

Organized by the Alzheimer's disease and related dementias (ADRD) Interest Group, this symposium aims to highlight unique approaches to address 1) ADRD risk reductions through social and biological factors, and 2) quality of life of those with dementia. The first two presentations introduce remote communication technologies used for behavioral inte...

Mosaic chromosomal alterations (mCAs) are structural alterations that are associated with mortality, age, cancer, cardiovascular disease, and diverse infections. The distribution of mCAs in long-lived subjects and individuals with familial longevity is not well described. We applied MOsaic CHromosomal Alteration (MoChA) caller on genome-wide genoty...

To examine the predictive abilities of 1) traditional neuropsychological (NP) test summary scores, and 2) error and process scores in separating cognitively resilient individuals from those who exhibit cognitive decline. A total of 69 participants from the Framingham Heart Study (FHS) Offspring and Omni 1 cohorts who had ≥1 NP assessment from 2011–...

Extreme longevity (EL) runs in families which supports the hypothesis that this is a genetically regulated trait. However, with the exception of APOE, genome-wide association studies (GWAS) of EL have not identified many genetic variants that replicate in independent studies. The majority of GWAS of EL have used imputed genotype data. Recently, the...

Higher levels of frailty, quantified by a frailty index (FI), may be linked to fatigue severity as tasks become more physically and mentally demanding. However, the association between frailty and fatigability—quantification of vulnerability to fatigue in relation to specific intensity and duration of activities—has not been assessed. Using cross-s...

With the goal of identifying metabolites that significantly correlate with the protective e2 allele of the apolipoprotein E (APOE) gene, we established a consortium of five studies of healthy aging and extreme human longevity with 3545 participants. This consortium includes the New England Centenarian Study, the Baltimore Longitudinal Study of Agin...

Age-related changes in immune cell composition and functionality are associated with multimorbidity and mortality. However, many centenarians delay the onset of aging-related disease suggesting the presence of elite immunity that remains highly functional at extreme old age. To identify immune-specific patterns of aging and extreme human longevity,...

Extended maternal age has been suggested as marker of delayed age-associated disabilities. We use the Long Life Family Study (LLFS) offspring generation to investigate the association between extended maternal age at last childbirth and healthy-aging endophenotypes. We hypothesize that women with extended maternal age at last childbirth will exhibi...

Neuropsychological assessment using the Boston Process Approach (BPA) suggests that an analysis of the strategy or the process by which tasks and neuropsychological tests are completed, and the errors made during test completion convey much information regarding underlying brain and cognition and are as important as overall summary scores. Research...

The Trail Making Test (TMT) is a neuropsychological test used to assess cognitive dysfunction. The TMT consists of two parts: TMT‐A requires connecting numbers 1 to 25 sequentially; TMT‐B requires connecting numbers 1 to 12 and letters A to L sequentially, alternating between numbers and letters. We propose using a digitally recorded version of TMT...

A surprising and well-replicated result in genetic studies of human longevity is that centenarians appear to carry disease-associated variants in numbers similar to the general population. With the proliferation of large genome-wide association studies (GWAS) in recent years, investigators have turned to polygenic scores to leverage GWAS results in...

We conducted a genome-wide association study (GWAS) of Digit Symbol Substitution Test (DSST) scores administered in 4207 family members of the Long Life Family Study (LLFS). Genotype data were imputed to the HRC panel of 64,940 haplotypes resulting in ~15M genetic variants with quality score > 0.7. The results were replicated using genetic data imp...

Extreme longevity is associated with resilience to Alzheimer’s disease. A major goal of centenarian studies is therefore to identify factors associated with maintaining cognitive function throughout life. Over the past year, two studies of centenarians and their offspring (age 60-110+ years) have pivoted from in-home assessments of cognitive and ph...

Some cognitive abilities, such as vocabulary, are resilient to brain aging, while others such as conceptual reasoning, memory, and processing speed, decline with age and their rate of decline is genetically regulated. Despite the strong genetic heritability of processing speed assessed by the digit symbol substitution test (DSST), previous studies...

Following disruptions to research, clinical trials, and support for individuals with Alzheimer’s disease and related dementias (ADRD), 2020 taught us important lessons about the need for creativity, flexibility, and resourcefulness during an urgent and global public health crisis. The COVID-19 pandemic showed that we have knowledge and technology t...

Background Perceived physical fatigability is highly prevalent in older adults and associated with mobility decline and other health consequences. We examined the prognostic value of perceived physical fatigability as an independent predictor of risk of death among older adults. Methods Participants (N = 2,906), mean age 73.5 [SD, 10.4] years, 54....

Objective In the wake of the coronavirus pandemic, teleneuropsychology utilization has increased. There is a need to characterize the first-hand experiences of individuals using teleneuropsychology, identify the common teleneuropsychology challenges, and devise practical strategies for mitigating/resolving these challenges. Method Survey data were...

Objective Teleneuropsychology (TeleNP) has experienced tremendous uptake during the coronavirus pandemic, and there is a need to document the challenges and practical advice for conducting remote cognitive assessments. Method 87 respondents (licensed neuropsychologists = 56; others [e.g., trainees] = 31) conducting TeleNP evaluations with adult po...

Background: The E4 allele of the APOE gene is known to be associated with cognitive impairment. However, a limited number of studies have examined the association between the E2 allele and longitudinal changes of cognitive function. Objective: To determine whether rates of cognitive change differ in carriers of the APOE E2 allele compared to oth...

Background: Coupling digital technology with traditional neuropsychological test performance allows collection of high-precision metrics that can clarify and/or define underlying constructs related to brain and cognition. Objective: To identify graphomotor and information processing trajectories using a digitally administered version of the Digi...

Background: A surprising and well-replicated result in genetic studies of human longevity is that centenarians appear to carry disease-associated variants in numbers similar to the general population. With the proliferation of large genome-wide association studies (GWAS) in recent years, investigators have turned to polygenic scores to leverage GWA...

Introduction: Cross-sectional analyses have associated familial longevity with better cognitive function and lower risk of cognitive impairment in comparison with individuals without familial longevity. The extent to which long-lived families also demonstrate slower rates of cognitive aging (i.e., change in cognition over time) is unknown. This st...

We conducted a genome-wide association study of 1320 centenarians from the New England Centenarian Study (median age = 104 years) and 2899 unrelated controls using >9 M genetic variants imputed to the HRC panel of ~65,000 haplotypes. The genetic variants with the most significant associations were correlated to 4131 proteins that were profiled in t...

Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 centenarians, 82 centenarians' offspring, and 65 age‐matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between centenarians and their offspring and controls (FDR <...

Objectives: Establish reliability, concurrent and convergent validity of the Pittsburgh Fatigability Scale (PFS) Mental subscale. Design: Cross-sectional. Setting: Older adults from two University of Pittsburgh registries, Baltimore Longitudinal Study of Aging (BLSA), and Long Life Family Study (LLFS). Participants: PFS Mental subscale valid...

In recent years, there has been growing interest in the problem of model selection in the Bayesian framework. Current approaches include methods based on computing model probabilities such as Stochastic Search Variable Selection (SSVS) and Bayesian LASSO and methods based on model choice criteria, such as the Deviance Information Criterion (DIC). M...

Apolipoprotein E ( APOE ) is an important risk factor for cognitive decline and Alzheimer’s disease in aging individuals. Among the 3 known alleles of this gene: e2, e3, and e4, the e4 allele is associated with faster cognitive decline and increased risk for Alzheimer’s and dementia, while the e2 allele has a positive effect on longevity, and possi...

There are 5.8 million Americans living with Alzheimer’s disease and more than 16 million Americans providing unpaid care for people with AD and related dementias. Since a treatment that can slow or stop progression of this disease has yet to be discovered, novel interventions are sorely needed to maintain cognitive function and quality of life amon...

Greater perceived physical fatigability is associated with physical functional decline, but few studies have examined its relation with cognition. Adults ≥60 (mean±SD age 73.7±10.5, 54.7% female, 99.6% white) from the Long Life Family Study (n=2355) completed the Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater fatigability) and a neurocogn...

Familial longevity and greater involvement in activities purported to build cognitive reserve (e.g. education, cognitively stimulating leisure activity) have both been associated with better cognitive function in later life, yet little is known about how these protective factors relate with one another. In this work, we modeled the associations amo...

Merging digital technologies with neuropsychological testing allows for collection of novel metrics that may reveal early, subtle differences in cognitive functioning. We examined whether digital pen metrics from the Clock Drawing Test (CDT) differentiate healthy agers (i.e., individuals with familial longevity) from spouses and individuals by APOE...

Effective exercise training and regular physical activity (PA) practice are important for healthy aging and are key modalities for chronic disease management. Approaches that enhance exercise prescriptions and adherence for older adults should be innovative and based on evidence. Thus, the exercise prescription should be tailored accordingly to the...

Background: The Long Life Family Study (LLFS) is a family based, prospective study of healthy aging and familial longevity. The study includes two assessments of cognitive function that were administered approximately 8 years apart. Objective: To test whether APOE genotype is associated with change of cognitive function in older adults. Methods...

Background Lower physical activity levels and greater fatigability contribute independently to slower gait speed in older adults. However, to fully understand the bidirectional relations between physical activity and fatigability, and to inform potential intervention strategies, we examined whether physical activity or fatigability explains more of...

Apolipoprotein E (APOE) is an important risk factor for cognitive decline and Alzheimer's disease in aging individuals. Among the 3 known alleles of this gene: e2, e3, and e4, the e4 allele is associated with faster cognitive decline and increased risk for Alzheimer's and dementia, while the e2 allele has a positive effect on longevity, and possibl...

The majority of research to understand the pathogenesis of and contributors to Alzheimer's disease (AD) pathology, dementia, and disease progression has focused on studying individuals who have the disease or are at increased risk of having the disease. Yet there may be much to learn from individuals who have a paradoxical decreased risk of AD sugg...

Maintaining good cognitive function at older age is important, but our knowledge of patterns and predictors of cognitive aging is still limited. We used Bayesian model-based clustering to group 5064 participants of the Long Life Family Study (ages 49–110 years) into clusters characterized by distinct trajectories of cognitive change in the domains...

Objective Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient deme...

Background: Fatigability is a construct that measures whole-body tiredness anchored to activities of a fixed intensity and duration; little is known about its epidemiology and heritability. Methods: Two generations of family members enriched for exceptional longevity and their spouses were enrolled (2006-2009) in the Long Life Family Study (LLFS...

APOE is a well-studied gene with multiple effects on aging and longevity. The gene has three alleles: e2, e3, and e4, whose frequencies vary by ethnicity. While the e2 is associated with healthy cognitive aging, the e4 allele is associated with Alzheimer’s disease and early mortality and therefore its prevalence among people with extreme longevity...

One in eight older adults in the US has Alzheimer’s disease or a related dementia, which are characterized by progressive cognitive and physical declines. The impact of dementia also goes beyond the individual since 92% of persons with dementia receive functional and emotional support from family members and other informal caregivers. The time dema...

We hypothesized large tumors (stage T3 or T4) are less likely to metastasize in centenarians compared to younger patients. We analyzed 2004 to 2015 Surveillance, Epidemiology, and End Results (SEER) data for the most common cancer types (breast, colon, lung, and prostate) among patients with T3 or T4 tumors and compared rates of M1 (presence of met...

A growing body of evidence has suggested a protective effect on cognition of the ε2 allele of APOE. To determine if APOE ε2 is associated with protection against cognitive decline, we analyzed repeated measures of the Telephone Interview for Cognitive Status (TICS) from 2,933 Long Life Family Study subjects and 679 New England Centenarian Study sub...

Fatigability, the likelihood of fatigue with lower versus higher levels of exertion, is associated with declines in physical function and disability and related to fitness. Thus, fatigability may be a good predictor of mortality. We examined this relationship in the Long Life Family Study (LLFS), an international family cohort enriched for longevit...

Older adults are vulnerable to negative recent life events (RLE) which deplete attentional resources and leads to cognitive exhaustion. Adaptive coping styles reduce perceived stress severity but their role on cognitive tiredness is unknown. We examined RLE and coping styles on perceived mental fatigability (Pittsburgh Fatigability Scale (PFS), 0-5...

We previously validated the physical, but not the mental subscale of the Pittsburgh Fatigability Scale (PFS). Thus, we aimed to validate the PFS mental subscale in 1,738 individuals aged ≥60 from the Long Life Family Study (55.5% female, age 74.8±11.1 years, PFS mental score 7.1±10.1, range 0-50). Confirmatory factor analysis with promax rotation s...

We examined the prevalence and heritability of perceived mental fatigability among older adults enrolled in the Long Life Family Study. Participants (N=2342; 55% female) self-administered the Pittsburgh Fatigability Scale (PFS; scores range 0-50; higher score=greater fatigability). Using the PFS mental subscale, we evaluated differences across age...

Exceptional aging has heritable components. One genetic risk factor for cognitive aging may be Apolipoprotein E (APOE), but it is unclear to what extent APOE relates to cognitive aging versus risk of Alzheimer’s disease. Cognitive aging may also be influenced by leukocyte telomere length (LTL), posited to be a marker of “biological age”. We examine...

Lower physical activity is cross-sectionally associated with greater fatigability; whether such a relationship holds for longitudinal changes in fatigability is under-studied. We examined this question in offspring (≥60 years, range 60-93y, 99.7% white; 53.2% female) enrolled in the Long Life Family Study, a two-generation cohort enriched for excep...

The strong heritability of extreme human longevity supports the hypothesis that this is a genetically-regulated trait. However, association studies focused on common genetic variants have discovered a limited number of longevity-associated genes. We conducted a genome-wide association study of 4,216 individuals including 1317 centenarians from the...

Motivation: Over the last decade, more diverse populations have been included in genome-wide association studies. If a genetic variant has a varying effect on a phenotype in different populations, genome-wide association studies applied to a dataset as a whole may not pinpoint such differences. It is especially important to be able to identify pop...

The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late‐onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an exte...

Objective: We hypothesize that mechanisms associated with extended reproductive age may overlap with mechanisms for the selection of genetic variants that slow aging and decrease risk for age-related diseases. Therefore, the goal of this analysis is to search for genetic variants associated with delayed age of menopause (AOM) among women in a stud...

We used Bayesian latent-group growth modelling to identify patterns of cognitive decline among Long Life Family participants in the domains of episodic memory, attention, processing speed and verbal fluency. For each neuropsychological test, we identified 4 or 5 large clusters of participants characterized by a 10% to 80% loss of the initial score....

Apolipoprotein E (APOE) is a well-studied gene with multiple effects on aging and longevity. The gene has 3 alleles: e2, e3 and e4 whose frequencies vary by ethnicity, and e4 is a known risk factor for Alzheimer’s, while e2 is associated with healthy aging and longevity. We analyzed ethnic specific effects of APOE alleles on extreme human longevity...

Introduction: Studies use multiple measures of cognitive function to assess for dementia. By examining concordance between objective and subjective questionnaires, we can gain insight into the benefits and drawbacks of these measures. Methods: New England Centenarian Study offspring participants (N=599, mean age 83.3+/-7.0 years) completed objectiv...

Several studies have observed that women who are able to naturally have children later in life tend to live longer. We hypothesize that the evolutionary pressure to extend the period of time in which women can bear children and therefore have the opportunity to have more of them could be a mechanism for the selection of genetic variants that slow a...

Fatigability is an important early predictor in the disablement pathway, yet little is known about its genetic basis or association with age and sex. We examined prevalence and heritability of perceived physical fatigability using the Pittsburgh Fatigability Scale (PFS, 0–50, higher score=higher fatigability) in the Long Life Family Study. PFS scor...

The Long Life Family Study, a longitudinal study of healthy aging among families with clustering for longevity, is a valuable cohort for identifying early markers of cognitive change. As digital metrics of cognitive performance may be more sensitive to cognitive change, we sought to implement a digital layer of data collection beyond standardized n...

Digital pen data from cognitive test performance can be used to calculate metrics that may reflect aspects of cognition not captured in traditional scores. As poor test scores can be caused by slow cognition or slow writing, measuring the pauses between pen strokes may be a better indicator of cognitive speed. The Digit Symbol Substitution Test was...

Introduction: Negative views of aging are associated with poor health behaviors and increased mortality. As many centenarians have been shown to delay or escape age-related illnesses, we hypothesized that their offspring would have better views of aging than their peers and that this positivity towards aging would contribute to their lower demonstr...

Introduction: Per previously published work, centenarian offspring have delayed disease onset and lower overall morbidity. Families not only have genetic variations in common, they also likely have important health-related behaviors in common as well. We sought to evaluate differences between the health behaviors of centenarian offspring and a refe...

A large portion of the baby boomer population will live beyond the age of 90 years, and entitlement programs and various insurance products have thus become interested in longevity risk. Beyond cohort life table predictions, actuaries have little to go on in determining which individuals or portions of populations are at increased risk of living to...

We assembled a collection of 28,297 participants from 7 studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity and the Health and Retirement Studies to investigate the association between the APOE alleles ɛ2, ɛ3...

Background Centenarian offspring have better health and lower mortality in comparison to referent cohorts however it is unknown whether they have preserved cognition at older ages. Methods This prospective study of 491 centenarian offspring and 270 referent participants without familial longevity (mean baseline age 75.5 years) from the New England...

Objectives: Purpose in life (PIL), a feeling of meaning and direction in life, is associated with favorable health outcomes including lower mortality and reduced risk of disease, disability, and cognitive impairment. Since centenarian offspring have been shown to have long health spans we sought to examine whether they have higher PIL than individ...

Recent work shows strong evidence of ancestry-based assortative mating in spouse pairs of the older generation of the Framingham Heart Study. Here, we extend this analysis to two studies of human longevity: the Long Life Family Study (LLFS), and the New England Centenarian Study (NECS). In the LLFS, we identified 890 spouse pairs spanning two gener...

Several studies have observed that women who are able to naturally have children later in life tend to live longer. We hypothesize that the evolutionary pressure to extend the period of time in which women can bear children and therefore have the opportunity to have more of them could be a mechanism for the selection of genetic variants that slow a...