Faculty Bibliography

Emerging evidence suggests that olfactory function is closely linked to memory function. The aims of this study were to assess whether olfactory and episodic memory functions follow similar age-related decline trajectories, to identify different patterns of decline, as well as predictors of the patterns. 1023 participants from the Memory and Aging Project were followed for up to 8 years with annual episodic memory and odor identification assessments. Trajectories were modelled using growth mixture models. Multivariate logistic regression was used to identify pattern predictors. Three patterns of joint trajectories were identified; Class 1- stable average performance in both functions (n=690, 67.4%); Class 2- stable average episodic memory and declining odor identification (n=231, 22.6%); and Class 3- decline in both functions (n= 102, 10.0%). Class predictors included age, sex, APOE ε4 status, cognitive activity level and BMI. Participants in Class 3 were most likely to develop dementia. Episodic memory and olfactory function show similar trajectories in aging. Such classification can contribute to a better understanding of the factors related to cognitive decline and dementia.

Down syndrome (DS) is a genetic disorder caused by the triplication of human chromosome 21, which results in neurological and physiological pathologies. These deficits increase during aging and are exacerbated by cognitive decline and increase of Alzheimer's disease (AD) neuropathology. A nontoxic, noninvasive treatment, maternal choline supplementation (MCS) attenuates cognitive decline in mouse models of DS and AD. To evaluate potential underlying mechanisms, laser capture microdissection of individual neuronal populations of MCS offspring was performed, followed by RNA sequencing and bioinformatic inquiry. Results at ~6 months of age (MO) revealed DS mice (the well-established Ts65Dn model) have significant dysregulation of select genes within the Type 2 Diabetes Mellitus (T2DM) signaling pathway relative to normal disomic (2N) littermates. Accordingly, we interrogated key T2DM protein hormones by ELISA assay in addition to gene and encoded protein levels in the brain. We found dysregulation of adiponectin (APN) protein levels in the frontal cortex of ~6 MO trisomic mice, which was attenuated by MCS. APN receptors also displayed expression level changes in response to MCS. APN is a potential biomarker for AD pathology and may be relevant in DS. We posit that changes in APN signaling may be an early marker of cognitive decline and neurodegeneration.

LAY ABSTRACT/UNASSIGNED:. They also underscore the need to assess multiple sources of information for increased accuracy.

One pathway by which environments of socioeconomic risk are thought to affect cognitive development is through stress physiology. The biological systems underpinning stress and attention undergo a sensitive period of development during infancy. Psychobiological theory emphasizes a dynamic pattern of context-dependent development, however, research has yet to examine how basal cortisol and attention dynamically covary across infancy in ecologically valid contexts. Thus, to address these gaps, we leveraged longitudinal, multilevel analytic methods to disentangle between- from within-person associations of hypothalamic-pituitary-adrenal (HPA) axis activity and executive attention behaviors across infancy. We use data from a large longitudinal sample (N = 1,292) of infants in predominantly low-income, nonurban communities at 7-, 15-, and 24-months of age. Using multilevel models, we investigated longitudinal associations of infant attention and basal cortisol levels and examined caregiving behaviors as moderators of this relationship. Results indicated a negative between- and within-person association between attention and cortisol across infancy and a within-person moderation by caregiver responsiveness. In other words, on the within-person level, higher levels of cortisol were concomitantly associated with lower infant attention across the first 2 years of life. However, variation in the caregiver's level of responsiveness either buffered or sensitized the executive attention system to the negative effects of physiological stress.

Rhythms of the brain are generated by neural oscillations across multiple frequencies. These oscillations can be decomposed into distinct frequency intervals associated with specific physiological processes. In practice, the number and ranges of decodable frequency intervals are determined by sampling parameters, often ignored by researchers. To improve the situation, we report on an open toolbox with a graphical user interface for decoding rhythms of the brain system (DREAM). We provide worked examples of DREAM to investigate frequency-specific performance of both neural (spontaneous brain activity) and neurobehavioral (in-scanner head motion) oscillations. DREAM decoded the head motion oscillations and uncovered that younger children moved their heads more than older children across all five frequency intervals whereas boys moved more than girls in the age of 7 to 9 years. It is interesting that the higher frequency bands contain more head movements, and showed stronger age-motion associations but weaker sex-motion interactions. Using data from the Human Connectome Project, DREAM mapped the amplitude of these neural oscillations into multiple frequency bands and evaluated their test-retest reliability. The resting-state brain ranks its spontaneous oscillation's amplitudes spatially from high in ventral-temporal areas to low in ventral-occipital areas when the frequency band increased from low to high, while those in part of parietal and ventral frontal regions are reversed. The higher frequency bands exhibited more reliable amplitude measurements, implying more inter-individual variability of the amplitudes for the higher frequency bands. In summary, DREAM adds a reliable and valid tool to mapping human brain function from a multiple-frequency window into brain waves.

The United States is the only high-income country that does not have a national policy mandating paid leave to working women who give birth. Increased rates of maternal employment post-birth call for greater understanding of the effects of family leave on infant development. This study examined the links between paid leave and toddler language, cognitive, and socioemotional outcomes (24-36 months; N = 328). Results indicate that paid leave was associated with better language outcomes, regardless of socioeconomic status. Additionally, paid leave was correlated with fewer infant behavior problems for mothers with lower levels of educational attainment. Expanding access to policies that support families in need, like paid family leave, may aid in reducing socioeconomic disparities in infant development.

A large number of studies have examined the association between advanced paternal age (APA) and risk of schizophrenia in offspring. Here we present an overview of epidemiological studies on this subject published since 2000, and systematically summarize their methodologies and results. Next, we discuss evidence to elucidate the potential mechanisms contributing to the association between APA and offspring schizophrenia, considering paternal psychiatric morbidity and genetic liability, maternal factors, and findings from family design studies. We propose that multiple mechanisms, including causal and non-causal pathways, contribute to the observed relationship between APA and schizophrenia in offspring, and conclude by highlighting the need for multi-disciplinary studies in disentangling these complex, non-mutually exclusive mechanisms.

Pregnancy is a critical time for the effects of environmental factors on children's development. The effect of added sugar intake on fetal development and pregnancy outcomes remains understudied despite increasing dietary intake in the United States. This study investigated the effect of added sugar on fetal programming by examining the association between maternal added sugar consumption, fetal movement, birth outcomes, and placental DNA methylation. Further, primary human fibroblasts were cultured under normal or high glucose conditions to assess the effect of high glucose exposure on cells' DNA methylation. We found that higher added sugar intake across pregnancy was associated with reduced 3rd-trimester fetal movement (p < .05) and shorter gestation (p < .01). Our sample size was not powered to detect the alteration of individual placental CpG with genome-wide significance. However, a secondary analysis suggested that added sugar consumption was associated with differential methylation of functionally related gene families across pregnancy. Consistent with this, high glucose exposure in primary cultured human fibroblasts altered the methylation of 17% of all CpGs, providing converging evidence for an effect of sugar on DNA methylation. Our results suggest that diets high in added sugar during pregnancy may have implications for offspring health via prenatal programming effects measurable before birth.