Holly A. Mack

Corpus callosum size, reaction time speed and variability in mild cognitive disorders and in a normative sample

Intra-individual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-individual RT variability would be associated with larger corpus callosum (CC) size in older adults, and that these associations would be stronger in adults with mild cognitive disorders. A normative sample (n=432) and a sample with mild cognitive disorders (n=57) were compared on CC area, RT mean and RT variability adjusting for age, sex, education, APOE genotype, smoking, alcohol consumption, grip strength, visual acuity, handedness and lung function. Samples did not differ in CC area or intra-cranial volume. In the normative sample, simple RT (SRT) and choice RT (CRT) were negatively associated with CC area but there were minimal associations between CC area and intra-individual RT variability. In the mild cognitive disorders sample, SRT, CRT and intra-individual variability on the SRT task were associated with CC area. Increased RT variability explained up to 12.7 percent of the variance in CC area in the sample with mild cognitive disorders, but less than 1 percent of the variance in CC area in the normative sample. There were no associations with APOE genotype. We conclude that intra-individual variability is associated with CC area in mild cognitive disorders, but not in normal aging. We propose that biological limits on reserve capacity must occur in mild cognitive disorders that result in stronger brain-behavior relationships being observed.

Quantitative Trait Loci Analysis of Structural and Material Skeletal Phenotypes in C57BL/6J and DBA/2 Second-Generation and Recombinant Inbred Mice

QTL analyses identified several chromosomal regions influencing skeletal phenotypes of the femur and tibia in BXD F2 and BXD RI populations of mice. QTLs for skeletal traits co‐located with each other and with correlated traits such as body weight and length, adipose mass, and serum alkaline phosphatase.

The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample

BackgroundWhile the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimers disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele [1] failed to find any effect of the *E4 allele on cognitive performance at ages 20–24, 40–44 or 60–64 years.MethodsIn this four year follow-up study, we reexamine the effect of *E4 in the sample of 2,021 individuals, now aged 65–69 years.ResultsPerformance on the Mini-Mental State Examination (MMSE) was significantly poorer for *E4 homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change.ConclusionIt is possible that *E4 carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65–69 years of age.

Adjusting data to body size : A comparison of methods as applied to quantitative trait loci analysis of musculoskeletal phenotypes

The aim of this study was to compare three methods of adjusting skeletal data for body size and examine their use in QTL analyses. It was found that dividing skeletal phenotypes by body mass index induced erroneous QTL results. The preferred method of body size adjustment was multiple regression.

The Relationship Between Cognition and Mortality in Patients with Stroke, Coronary Heart Disease, or Cancer

Numerous studies have reported an association between cognitive impairment and an increased risk for mortality. Most results are from large epidemiological studies and control for medical conditions that may relate to cognitive decline, as well as an increased mortality risk. The aim of this review was to evaluate the association between cognitive performance and mortality within patient samples of stroke, cancer, or coronary heart disease. After reviewing the PubMed literature for articles on stroke, cancer, and cardiovascular related illnesses, 47 longitudinal studies were identified that met the cognition/mortality search criteria. In general, the results demonstrated that within the clinical groups studied, cognitive performance and cognitive impairment both predict mortality, although results were less consistent for coronary heart disease. This study adds further support for the ubiquity of the association of cognitive performance with health outcomes and mortality. Optimizing health has implication...

Prevalence of dementia in urban and regional Aboriginal Australians

This study aimed to determine the prevalence of dementia in collaboration with urban/regional Aboriginal communities.

Bone, muscle, and physical activity: structural equation modeling of relationships and genetic influence with age

Correlations among bone strength, muscle mass, and physical activity suggest that these traits may be modulated by each other and/or by common genetic and/or environmental mechanisms. This study used structural equation modeling (SEM) to explore the extent to which select genetic loci manifest their pleiotropic effects through functional adaptations commonly referred to as Wolffs law. Quantitative trait locus (QTL) analysis was used to identify regions of chromosomes that simultaneously influenced skeletal mechanics, muscle mass, and/or activity‐related behaviors in young and aged B6×D2 second‐generation (F2) mice of both sexes. SEM was used to further study relationships among select QTLs, bone mechanics, muscle mass, and measures of activity. The SEM approach provided the means to numerically decouple the musculoskeletal effects of mechanical loading from the effects of other physiological processes involved in locomotion and physical activity. It was found that muscle mass was a better predictor of bone mechanics in young females, whereas mechanical loading was a better predictor of bone mechanics in older females. An activity‐induced loading factor positively predicted the mechanical behavior of hindlimb bones in older males; contrarily, load‐free locomotion (i.e., the remaining effects after removing the effects of loading) negatively predicted bone performance. QTLs on chromosomes 4, 7, and 9 seem to exert some of their influence on bone through actions consistent with Wolffs Law. Further exploration of these and other mechanisms through which genes function will aid in development of individualized interventions able to exploit the numerous complex pathways contributing to skeletal health.

Childhood Stress and Adversity is Associated with Late-Life Dementia in Aboriginal Australians

OBJECTIVES High rates of dementia have been observed in Aboriginal Australians. This study aimed to describe childhood stress in older Aboriginal Australians and to examine associations with late-life health and dementia. DESIGN A cross-sectional study with a representative sample of community-dwelling older Aboriginal Australians. SETTING Urban and regional communities in New South Wales, Australia. PARTICIPANTS 336 Aboriginal and/or Torres Strait Islander Australians aged 60-92 years, of whom 296 were included in the current analyses. MEASUREMENTS Participants completed a life course survey of health, well-being, cognition, and social history including the Childhood Trauma Questionnaire (CTQ), with consensus diagnosis of dementia and Alzheimer disease. RESULTS CTQ scores ranged from 25-117 (median: 29) and were associated with several adverse childhood indicators including separation from family, poor childhood health, frequent relocation, and growing up in a major city. Controlling for age, higher CTQ scores were associated with depression, anxiety, suicide attempt, dementia diagnosis, and, specifically, Alzheimer disease. The association between CTQ scores and dementia remained significant after controlling for depression and anxiety variables (OR: 1.61, 95% CI: 1.05-2.45). In contrast, there were no significant associations between CTQ scores and smoking, alcohol abuse, diabetes, or cardiovascular risk factors. CONCLUSIONS Childhood stress appears to have a significant impact on emotional health and dementia for older Aboriginal Australians. The ongoing effects of childhood stress need to be recognized as people grow older, particularly in terms of dementia prevention and care, as well as in populations with greater exposure to childhood adversity, such as Aboriginal Australians.

Blood pressure and heart rate QTL in mice of the B6/D2 lineage sex differences and environmental influences

A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on seven occasions by the tail cuff procedure. The tests were conducted in 395 F(2) adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F(2) data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5. New suggestive QTL emerged for SBP on Chr 3 (female-specific) and 8 and for HR on Chr 11 for measurements recorded several weeks after mice had undergone stressful blood sampling procedures. The two statistically significant HR QTL were confirmed by analyses of BXD RI strain means. Male and female F(2) mice did not differ in SBP or HR but RI strain analyses showed pronounced strain-by-sex interactions and a negative genetic correlation between the two measures in both sexes. Evidence for a role for mitochondrial DNA was found for both HR and SBP. QTL for HR and SBP may differ in males and females and may be sensitive to different environmental contexts.

Comparison of Three Cognitive Screening Tools in Older Urban and Regional Aboriginal Australians

Background: Validated cognitive screening tools for use in urban and regional Aboriginal populations in Australia are lacking. Methods: In a cross-sectional community-based study, 235 participants were assessed on the Mini-Mental State Examination (MMSE), the Rowland Universal Dementia Assessment Scale (RUDAS) and an urban modification of the Kimberley Indigenous Cognitive Assessment (mKICA). Performance on these cognitive screening tools was compared to dementia diagnosis by clinical consensus. Results: All tests were culturally acceptable with good psychometric properties. Receiver operating characteristic curve analyses revealed that the MMSE and mKICA were the most accurate. Conclusion: The MMSE is an effective cognitive screening tool in urban Aboriginal populations. The mKICA is a good alternative when illiteracy, language or cultural considerations deem it appropriate. The RUDAS also has adequate validity in this population.