Amber Watts

Reduced Lean Mass in Early Alzheimer Disease and Its Association With Brain Atrophy

OBJECTIVE To examine body composition in individuals with early AD and without dementia and its relation to cognition and brain volume. DESIGN Cross-sectional case-control study. PARTICIPANTS Individuals without dementia (Clinical Dementia Rating, 0; n = 70) and with early-stage AD (Clinical Dementia Rating, 0.5 or 1; n = 70) in the Alzheimer and Memory Program at the University of Kansas School of Medicine. MAIN OUTCOME MEASURES Participants were evaluated with brain magnetic resonance imaging (MRI), neuropsychological testing, and dual-energy x-ray absorptiometry to determine whole-body fat and lean masses. Body mass index was calculated as weight in kilograms divided by height in meters squared. RESULTS Lean mass was reduced in persons with early AD compared with controls without dementia (F = 7.73; P = .006) after controlling for sex. Whole-brain volume (beta = .20; P < .001), white matter volume (beta = .19; P < .001), and global cognitive performance (beta = .12; P = .007) were associated with lean mass (dependent variable) when controlling for age and sex. The total body fat and percentage of body fat values were not different across groups or related to cognition and brain volume. CONCLUSION Loss of lean mass is accelerated in AD and is associated with brain atrophy and cognitive performance, perhaps as a direct or indirect consequence of AD pathophysiology or through shared mechanisms common to both AD and sarcopenia.

Inflammation as a potential mediator for the association between periodontal disease and Alzheimer’s disease

Periodontal disease (PDD) is associated with increased risk of cardiovascular disease, cerebrovascular disease, and mortality in many studies, while other studies have begun to suggest an association of PDD with Alzheimer’s disease (AD). This paper discusses how infectious pathogens and systemic infection may play a role in AD. The roles of infection and inflammation are addressed specifically with regard to known AD pathologic lesions including senile plaques, neuron death, neurofibrillary tangles, and cerebrovascular changes. A testable model of proposed pathways between periodontal infection and AD is presented including three possible mechanisms: a) direct effects of infectious pathogens, b) inflammatory response to pathogens, and c) the effects on vascular integrity. The role of gene polymorphisms is discussed, including apolipoprotein (APOE) ɛ4 as a pro-inflammatory and pro-infection genotype.

Metabolic Syndrome and Cognitive Decline in Early Alzheimer’s Disease and Healthy Older Adults

Metabolic syndrome (MetS) is a cluster of risk factors (i.e., abdominal obesity, hypertension, dyslipidemia, glucose and insulin dysregulation) that is associated with cardiovascular disease, diabetes, and dementia. Recent studies addressing the association of MetS with cognitive performance and risk for dementia report mixed results. An important step in clarifying these conflicting results is determining whether cognition is influenced by the effects of individual MetS components versus the additive effects of multiple components. We assessed the effect of MetS on cognitive performance and decline over two years in 75 cases of early Alzheimers disease (AD) and 73 healthy older adult controls in the Brain Aging Project. Using factor analytic techniques, we compared the effect of a combined MetS factor to the effect of individual MetS components on change in attention, verbal memory, and mental status. In healthy controls, a combined MetS factor did not significantly predict cognitive performance, though higher insulin predicted poorer cognitive performance outcomes. In the AD group, higher scores on a combined MetS factor predicted better cognitive outcomes. Our findings suggest that MetS does not have the same association with cognitive decline in healthy older adults and those with early AD. We suggest that individual MetS components should not be evaluated in isolation and that careful methodological approaches are needed to understand the timing and non-linear relationships among these components over time.

Neuropsychiatric profiles in dementia.

We compared patterns of neuropsychiatric symptoms across 4 dementia types [Alzheimer disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB), and Parkinson disease dementia], and 2 mixed groups (AD/VAD and AD/DLB) in sample of 2,963 individuals from the National Alzheimers Coordinating Center Uniform Data Set between September 2005 and June 2008. We used confirmatory factor analysis to compare neuropsychiatric symptom severity ratings made by collateral sources on the Neuropsychiatric Inventory Questionnaire for people with Clinical Dementia Rating scores of 1 or higher. A 3-factor model of psychiatric symptoms (mood, psychotic, and frontal) was shared across all dementia types. Between-group comparisons revealed unique neuropsychiatric profiles by dementia type. The AD group had moderate levels of mood, psychotic, and frontal symptoms whereas VAD exhibited the highest levels and Parkinson disease dementia had the lowest levels. DLB and the mixed dementias had more complex symptom profiles. Depressed mood was the dominant symptom in people with mild diagnoses. Differing psychiatric symptom profiles provide useful information regarding the noncognitive symptoms of dementia.

Exercise and Depressive Symptoms in Older Adults: A Systematic Meta-Analytic Review

Depressive symptoms are common in older adults, but antidepressant medications may be contraindicated or poorly tolerated in this population. Intervention studies demonstrate that exercise may be an effective alternative. This meta-analysis included 41 randomized controlled trials of aerobic and nonaerobic exercise interventions investigating the effect of exercise on depressive symptoms in adults aged 60 or older. A random effects model demonstrated that exercise was associated with significantly lower depression severity (SMD = 0.57, 95% CI 0.36-0.78). This effect was not significantly different for different ages of participants, types of control groups, or types of exercise interventions. Studies requiring a diagnosis of depression had significantly greater mean effect sizes than studies that did not require a depression diagnosis (Qbet = 6.843, df = 1, p = .009). These findings suggest that exercise is an effective treatment option for older individuals with depressive symptoms.

Measuring Physical Activity in Older Adults With and Without Early Stage Alzheimer's Disease

We compared subjective reports of physical activity with objective measures of physical fitness including cardiorespiratory capacity, body composition, and physical performance in 146 older adults with and without early stage Alzheimers disease (ESAD). Respondents reported primarily unstructured and low-intensity activities, including walking and housework. Individuals with ESAD participated in fewer and lower intensity physical activities than those without ESAD. In those without ESAD, housework was related to lower body mass index, leisure walking was related to faster speed on a timed walking test, and participation in sports was related to higher peak oxygen intake. In individuals with ESAD, reported physical activities did not predict any of the physical fitness, body composition, or physical performance measures. We conclude that measures of physical activity require expansion of unstructured and low-intensity activities to improve sensitivity in sedentary populations, especially in older adults with ESAD.

Neighborhood Integration and Connectivity Predict Cognitive Performance and Decline.

Objective: Neighborhood characteristics may be important for promoting walking, but little research has focused on older adults, especially those with cognitive impairment. We evaluated the role of neighborhood characteristics on cognitive function and decline over a 2-year period adjusting for measures of walking. Method: In a study of 64 older adults with and without mild Alzheimer’s disease (AD), we evaluated neighborhood integration and connectivity using geographical information systems data and space syntax analysis. In multiple regression analyses, we used these characteristics to predict 2-year declines in factor analytically derived cognitive scores (attention, verbal memory, mental status) adjusting for age, sex, education, and self-reported walking. Results: Neighborhood integration and connectivity predicted cognitive performance at baseline, and changes in cognitive performance over 2 years. The relationships between neighborhood characteristics and cognitive performance were not fully explained by self-reported walking. Discussion: Clearer definitions of specific neighborhood characteristics associated with walkability are needed to better understand the mechanisms by which neighborhoods may impact cognitive outcomes. These results have implications for measuring neighborhood characteristics, design and maintenance of living spaces, and interventions to increase walking among older adults. We offer suggestions for future research measuring neighborhood characteristics and cognitive function.

A Combined Measure of Vascular Risk for White Matter Lesions

BACKGROUND Though hypertension is a commonly studied risk factor for white matter lesions (WMLs), measures of blood pressure may fluctuate depending on external conditions resulting in measurement error. Indicators of arterial stiffening and reduced elasticity may be more sensitive indicators of risk for WMLs in aging; however the interdependent nature of vascular indicators creates statistical complications. OBJECTIVE The purpose of the study was to determine whether a factor score comprised of multiple vascular indicators would be a stronger predictor of WMLs than traditional measures of blood pressure. METHODS In a sample of well-characterized nondemented older adults, we used a factor analytic approach to account for variance common across multiple vascular measures while reducing measurement error. The result was a single factor score reflecting arterial stiffness and reduced elasticity. We used this factor score to predict white matter lesion volumes acquired via fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging. RESULTS The combined vascular factor score was a stronger predictor of deep WML (β = 0.42, p < 0.001) and periventricular WML volumes (β = 0.49, p < 0.001). After accounting for the vascular factor, systolic and diastolic blood pressure measurements were not significant predictors. CONCLUSIONS This suggests that a combined measure of arterial elasticity and stiffening may be a stronger predictor of WMLs than systolic and diastolic blood pressure accounting for the multicollinearity associated with a variety of interrelated vascular measures.

Expectations Regarding Aging, Physical Activity, and Physical Function in Older Adults:

Objective: The present study examined how expectations regarding aging (ERA) influence physical activity participation and physical function. Method: We surveyed 148 older adults about their ERA (ERA-38), health-promoting lifestyles (HPLP-II), and self-rated health (RAND-36). We tested the mediating effect of physical activity on the relationships between ERA and physical function. Results: Positive expectations were associated with more engagement in physical activity (B = 0.016, p < .05) and better physical function (B = 0.521, p < .01). Physical activity mediated the relationship between ERA and physical function (B = 5.890, p < .01, indirect effect 0.092, CI = [0.015, 0.239]). Discussion: ERA play an important role in adoption of physically active lifestyles in older adults and may influence health outcomes, such as physical function. Future research should evaluate whether attempts to increase physical activity are more successful when modifications to ERA are also targeted.

Intra-Individual Variability of Physical Activity in Older Adults With and Without Mild Alzheimer's Disease.

Physical activity shows promise for protection against cognitive decline in older adults with and without Alzheimer’s disease (AD). To better understand barriers to adoption of physical activity in this population, a clear understanding of daily and weekly activity patterns is needed. Most accelerometry studies report average physical activity over an entire wear period without considering the potential importance of the variability of physical activity. This study evaluated individual differences in the amount and intra-individual variability of physical activity and determined whether these differences could be predicted by AD status, day of wear, age, gender, education, and cardiorespiratory capacity. Physical activity was measured via accelerometry (Actigraph GT3X+) over one week in 86 older adults with and without AD (n = 33 and n = 53, respectively). Mixed-effects location-scale models were estimated to evaluate and predict individual differences in the amount and intra-individual variability of physical activity. Results indicated that compared to controls, participants with AD averaged 21% less activity, but averaged non-significantly greater intra-individual variability. Women and men averaged similar amounts of physical activity, but women were significantly less variable. The amount of physical activity differed significantly across days of wear. Increased cardiorespiratory capacity was associated with greater average amounts of physical activity. Investigation of individual differences in the amount and intra-individual variability of physical activity provided insight into differences by AD status, days of monitor wear, gender, and cardiovascular capacity. All individuals regardless of AD status were equally consistent in their physical activity, which may have been due to a highly sedentary sample and/or the early disease stage of those participants with AD. These results highlight the value of considering individual differences in both the amount and intra-individual variability of physical activity.