Thomas Fairchild

A blood-based algorithm for the detection of Alzheimer's disease.

Background: We previously created a serum-based algorithm that yielded excellent diagnostic accuracy in Alzheimer’s disease. The current project was designed to refine that algorithm by reducing the number of serum proteins and by including clinical labs. The link between the biomarker risk score and neuropsychological performance was also examined. Methods: Serum-protein multiplex biomarker data from 197 patients diagnosed with Alzheimer’s disease and 203 cognitively normal controls from the Texas Alzheimer’s Research Consortium were analyzed. The 30 markers identified as the most important from our initial analyses and clinical labs were utilized to create the algorithm. Results: The 30-protein risk score yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91, respectively. When combined with demographic data and clinical labs, the algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94, respectively. In linear regression models, the biomarker risk score was most strongly related to neuropsychological tests of language and memory. Conclusions: Our previously published diagnostic algorithm can be restricted to only 30 serum proteins and still retain excellent diagnostic accuracy. Additionally, the revised biomarker risk score is significantly related to neuropsychological test performance.

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.

Refinement and expansion of the Texas Alzheimer's research consortium serum-based diagnostic algorithm for Alzheimer's disease

To link straight to related open access papers, reviews and relevant Cochrane DTA reviews CDCIGwill expand its existing, comprehensive library of pdfs of all reports of dementia related interventions to include reports on diagnostic test accuracy.Conclusions: The systematic expansion of ALOIS to include studies of diagnostic test accuracy is an important move in the effort to provide review authors, researchers and other stakeholders with easy access to content-rich comprehensive information about studies. CDCIG continues to welcome contributions to the maintenance of ALOIS from students, researchers, and graduate level caregivers.

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging

OBJECTIVES To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. DESIGN Prospective multicenter cross-sectional study with a longitudinal arm. SETTING Outpatient memory diagnostic clinics in New York and Texas. PARTICIPANTS Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. MEASUREMENTS Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. RESULTS For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. CONCLUSIONS Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals.

A Serum protein-based algorithm for the detection of Alzheimer's disease

Conclusions: These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. A disproportionate number of inflammatory and vascular markers were weighted most heavily in the analyses. Additionally, these markers consistently distinguished cases from controls in significant analysis of microarray, logistic regression, and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.

Serum Granulocyte Colony-Stimulating Factor and Alzheimer's Disease

BACKGROUND Granulocyte colony-stimulating factor (G-CSF) promotes the survival and function of neutrophils. G-CSF is also a neurotrophic factor, increasing neuroplasticity and suppressing apoptosis. METHODS We analyzed G-CSF levels in 197 patients with probable Alzheimers disease (AD) and 203 cognitively normal controls (NCs) from a longitudinal study by the Texas Alzheimers Research and Care Consortium (TARCC). Data were analyzed by regression with adjustment for age, education, gender and APOE4 status. RESULTS Serum G-CSF was significantly lower in AD patients than in NCs (β = -0.073; p = 0.008). However, among AD patients, higher serum G-CSF was significantly associated with increased disease severity, as indicated by lower Mini-Mental State Examination scores (β = -0.178; p = 0.014) and higher scores on the global Clinical Dementia Rating (CDR) scale (β = 0.170; p = 0.018) and CDR Sum of Boxes (β = 0.157; p = 0.035). CONCLUSIONS G-CSF appears to have a complex relationship with AD pathogenesis and may reflect different pathophysiologic processes at different illness stages.

An inflammatory endophenotype of Alzheimer's disease

Robert Barber, Guanghua Xiao, Sid O’Bryant, Justin Saunders, Joan Reisch, Rachelle Doody, Thomas Fairchild, Perrie Adams, Christie Ballantyne, Ramon Diaz-Arrastia The Texas Alzheimer’s Research Consortium Texas Alzheimer’s Research Consortium, Dallas, TX, USA; University of Texas Southwestern Medical Center, Dallas, TX, USA; Texas Tech University Health Science Center, Lubbock, TX, USA; Baylor College of Medicine, Houston, TX, USA; University of North Texas Health Science Center, Fort Worth, TX, USA. Contact e-mail: rbarber516@yahoo.com