April Wiechmann

Biomarkers of Vascular Risk, Systemic Inflammation, and Microvascular Pathology and Neuropsychiatric Symptoms in Alzheimer's Disease

Numerous serum and plasma based biomarkers of systemic inflammation have been linked to both neuropsychiatric disorders and Alzheimers disease (AD). The present study investigated the relationship of clinical biomarkers of cardiovascular risk (cholesterol, triglycerides, and homocysteine) and a panel of markers of systemic inflammation (CRP, TNF-α, IL1-ra, IL-7, IL-10, IL-15, IL-18) and microvascular pathology (ICAM-1, VCAM-1) to neuropsychiatric symptoms in a sample with mild AD. Biomarker data was analyzed on a sample of 194 diagnosed with mild to moderate probable AD. The sample was composed of 127 females and 67 males. The presence of neuropsychiatric symptoms was gathered from interview with caretakers/family members using the Neuropsychiatric Inventory. For the total sample, IL-15, VCAM (vascular adhesion molecule), and triglycerides were significantly and negatively related to number of neuropsychiatric symptoms, and total cholesterol and homocysteine were positively related and as a group accounted for 16.1% of the variance. When stratified by gender, different patterns of significant biomarkers were found with relationships more robust for males for both total symptoms and symptom clusters. A combination of biomarkers of systemic inflammation, microvascular pathology, and clinical biomarkers of cardiovascular risk can account for a significant portion of the variance in the occurrence of neuropsychiatric symptoms in AD supporting a vascular and inflammatory component of psychiatric disorders found in AD. Gender differences suggest distinct impact of specific risks with total cholesterol, a measure of cardiovascular risk, being the strongest marker for males and IL-15, a marker of inflammation, being the strongest for females.

The Utility of the Spatial Span in a Clinical Geriatric Population

ABSTRACT Spatial Span subtest of the Wechsler Memory Scale has been viewed as an indicator of working memory and visuospatial processing. The current study examined the impact of cognitive impairment and its severity on Spatial Span performance. A neuropsychological battery including Spatial Span was administered to 538 individuals (65–89) who were grouped by consensus into Alzheimers disease, Vascular Dementia, Amnestic Mild Cognitive Impairment, Non-Amnestic Mild Cognitive Impairment and cognitively normal. Increase in level of impairment resulted in a decrease in Spatial Span Total Score. A weak relationship between age and Spatial Span Total Score was found. Spatial Span Forward remains relatively stable regardless of level of impairment. Spatial Span Backward was more sensitive to severity. No significant differences were found between individuals diagnosed with Alzheimers disease and those with Vascular Dementia suggesting similar deficit patterns in the cognitive abilities measured by the Spatial Span. Mild Cognitive Impairment groups and normals did not differ suggesting visuospatial processes are not affected early in the dementing process.

Role of Parental Stress on Pediatric Feeding Disorders

The study examined the relation between parental anxiety and child feeding progress. Eighteen sets of parent and G-tube-fed child dyads participated. Caloric intake was recorded daily as the outcome measure of treatment progression. Parental anxiety was measured subjectively (self-report questionnaires) and objectively (salivary cortisol). Objective parental anxiety increased significantly (p < .001) when parents went from simply observing to actually feeding the child. There was, however, no direct relation between parental stress and caloric intake. Exploratory analyses of documented behavioral observations during feeding revealed a significant increase (p <. 001) in the childs negative behaviors with parental feeding, as opposed to staff feeding. Based on the results, further research to investigate parent–child dynamics during feeding is warranted.

The Four-Point Scoring System for the Clock Drawing Test Does Not Differentiate between Alzheimer's Disease and Vascular Dementia

The purpose of this study was to explore the sensitivity and specificity of the Clock Drawing Test by using a widely employed four-point scoring system to discriminate between patients with Alzheimers disease or vascular dementia. Receiver operating characteristic analysis indicated that the Clock Drawing Test was able to distinguish between normal elders and those with a dementia diagnosis. The cutoff score for differentiating patients with Alzheimers disease from normal participants was = 3. The cutoff score for differentiating those with vascular disease from normal participants was = 3. Overall, the four-point scoring system demonstrated good sensitivity and specificity for identifying cognitive dysfunction associated with dementia; however, the current findings do not support the utility of the four-point scoring system in discriminating Alzheimers disease and vascular dementia.

The Impact of APOE Status on Relationship of Biomarkers of Vascular Risk and Systemic Inflammation to Neuropsychiatric Symptoms in Alzheimer's Disease

Research on the link between APOEε4 and neuropsychiatric symptoms (NPS) in Alzheimers disease (AD) has been inconsistent. Previous work has shown a relationship between serum biomarkers of vascular risk and inflammation and NPS in AD. The current study investigated the impact of APOEε4 status on the relationship between biomarkers of cardiovascular risk, systemic inflammation, and NPS. The sample was drawn from the TARCC Longitudinal Research Cohort; the final sample of 190 consisted of 124 females and 66 males meeting the diagnostic criteria for mild to moderate AD. 115 individuals were APOEε4 carriers and 75 were non-carriers. Serum-based clinical biomarkers of vascular risk and biomarkers of inflammation related to AD were analyzed. NPS data was gathered from caretakers/family members using the Neuropsychiatric Inventory. The significant biomarkers differed for carriers and non-carriers with IL15 being a negative biomarker of total NPS accounting for 12% of the variance for carriers and IL18 and TNFα negative predictors for non-carriers (18% of variance). Patterns related to specific symptoms were similar. Stratification by gender revealed significant biomarkers of total NPS for female carriers were negative IL15 and IL1ra (18% of variance) and for female non-carriers were negative IL18 and positive homocysteine. Total cholesterol was a positive biomarker of total NPS for both male carriers (36% of variance) and non-carriers (negative TNFα and total cholesterol, 32% of variance). These findings suggest that dysregulation of inflammatory activity is related to NPS, that cholesterol is a significant factor in the occurrence of NPS, and that gender and APOE status need to be considered.

Total Cholesterol and Neuropsychiatric Symptoms in Alzheimer's Disease: The Impact of Total Cholesterol Level and Gender

Background: Neuropsychiatric symptoms (NPS) in Alzheimers disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD. Methods: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimers Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed. Results: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC. Conclusion: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.

CHARACTERISTICS OF COGNITIVELY NORMAL OLDER MEXICAN AMERICANS AND NON-HISPANIC WHITES WITH SUBJECTIVE COGNITIVE COMPLAINTS

of the cohort was 856 7.0 years; 79% were women; mean MMSE was 29.06 1.1. The genotype makeup of the group was: e4+ 1⁄4 17 (all e3/e4); e4(e3/e3, (e2/e3) 1⁄4 72. A mean of 321 nights per participant of nighttime activity was used to estimate total sleep time. APOE e4+ carriers’ mean nightly sleep time was 6.8 hours (SD 1.4); APOE e4 carriers’ mean nightly sleep time was 7.4 hours (SD 1.6), p1⁄40.16. APOE e4 carriers had higher night-to-night variability in sleep time over the one-year monitoring period (mean 1⁄4 2.0 hours) compared to thosewithout APOE e4 (mean1⁄4 1.6 hours); (p < 0.01). Self-reported hours of sleep were correlated with the objective sleep times (Spearman correlation 1⁄4 .40; p < 0.001). Conclusions: The APOE e4 genotype is associated with greater nighttime variability in sleep time, but not mean sleep time in cognitively normal older adults. Self-report measures in this cognitively intact group regardless of APOE genotype were moderately correlated with sensor based nightly measurement. Whether night-to-night sleep metric variability is an early indicator of increased risk for MCI and subsequent ADwill require longitudinal follow-up.

THE RELATIONSHIP OF METABOLIC AND INFLAMMATORY BIOMARKERS TO SUBJECTIVE COGNITIVE COMPLAINTS IN A SAMPLE OF COGNITIVELY NORMAL MEXICAN-AMERICANS

on 1.5 T magnetic resonance images and normalized by the cerebellum gray matter uptake. Then, the association between (FBB) PET SUVR variables with TP and FP Ab40 and Ab42 levels was determined in SCD subjects. Obtained data were analyzed using correlations and linear regression-based methods. Finally, logistic regression and area under the receiver operating characteristic curve (AUROC) were calculated to evaluate the discrimination of brain amyloidosis. Results: (FBB) PET SUVR significantly correlated with TP Ab42/Ab40 ratio (r1⁄40.214, p1⁄42.59E-04, CI(95%) [-0.063 -0.019; logarithmic scale]. This observation resisted covariation with age, education, gender and APOE Ɛ4 carrier status. A total of 18 (9.05%) individuals had PET positive (FBB PET SUVR > 1.45). Multivariate analyses including age, APOE and logarithmic ratio TP Ab42/ Ab40 was the most discriminant model predicting brain amyloidosis (AUROC1⁄4 0.82). Conclusions: Brain and plasma Ab levels are partially correlated in individuals diagnosed with SCD. Ab measurements in plasma might help to identify SCD people with brain amyloidosis and to reduce the screening failure rate in ongoing pre-clinical AD studies. Independent replication of these findings is warranted.

THE TEXAS ASSESSMENT OF PROCESSING SPEED (TAPS) PERFORMANCE IN PATIENTS WITH COGNITIVE IMPAIRMENT

intensive lipid lowering was associated with an improved ACE-R, animal naming and TMT A time. Further trials investigating intensive lipid lowering therapy may be warranted. References: Bath PM, Scutt P, Blackburn DJ, Ankolekar S, Krishnan K, et al. (2017) Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot ‘Prevention of Decline in Cognition after Stroke Trial’ (PODCAST) Randomised Controlled Trial. PLOS ONE 12(1): e0164608. http://dx.doi.org/10.1371/journal.pone.0164608.

IL-7 and Depression: The importance of gender and blood fraction.

Interleukin 7 (IL-7) is involved in B and T cell development and differentiation. Recent work suggests IL-7 may be altered in depression; however, we have previously shown that gender and blood fraction oftentimes impacts putative biomarker relationships among those with and without Alzheimers disease (AD). The current study examined the impact of blood fraction (serum versus plasma) and gender on the IL7 depression link in a sample of elders with and without AD. Non-fasting serum (150 AD cases 150 controls) and plasma (100 AD cases, 100 controls) IL-7 levels were assayed via electrochemiluminescence. The correlation between serum and plasma for IL-7 was 0.34. In the total sample, serum (r(2)=0.16, p=0.006) and plasma (r(2)=-0.20, p=0.007) IL-7 levels were significantly, but inversely, correlated with GDS-30 scores. When split by gender, serum IL-7 levels were significantly positively associated with GDS scores among men (r(2)=0.34, p=0.001) whereas plasma IL-7 levels (r(2)=-0.23, p=0.008) were significantly negatively associated with GDS scores among women. A logistic regression model predicting depression status (GDS30>=10) included age, gender, education, plasma, and serum IL-7 levels, found both significantly associated with depression status, but in opposite directions. Our findings support a significant link between IL-7 and depression; however, we further highlight the importance of blood fraction and gender when examining this relationship. Additionally, these findings further support the need for additional work that could lead to targeted therapeutic interventions utilizing anti-inflammatory medications for individuals with depression.