Combining select neuropsychological assessment with blood-based biomarkers to detect mild Alzheimer's disease: a molecular neuropsychology approach.

BACKGROUND Current work has sought to establish a rapid and cost effective means of screening for Alzheimer's disease (AD) with the most recent findings showing utility of integrating blood-based biomarkers with cognitive measures. OBJECTIVE The current project sought to create a combined biomarker-cognitive profile to detect mild AD. METHODS Data was analyzed from 266 participants (129 AD cases [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas Alzheimer's Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochemiluminescence. Logistic Regression was utilized to detect early AD using two serum biomarkers (TNFα and IL7), demographic information (age), and one neuropsychological measure (Clock 4-point) as predictor variable. Disease severity was determined via Clinical Dementia Rating (CDR) scale global scores. RESULTS In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5-1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall accuracy of 0.91. CONCLUSIONS The combination of demographics, two biomarkers, and one cognitive test created a biomarker-cognitive profile that was highly accurate in detecting the presence of AD, even in the very early stages.

[1]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[2]  Guanghua Xiao,et al.  Validation of a serum screen for Alzheimer's disease across assay platforms, species, and tissues. , 2014, Journal of Alzheimer's disease : JAD.

[3]  M. Mapstone Neuropsychological Assessment, 4th Edition , 2005, Neurology.

[4]  Magda Tsolaki,et al.  Combinatorial markers of mild cognitive impairment conversion to Alzheimer's disease--cytokines and MRI measures together predict disease progression. , 2011, Journal of Alzheimer's disease : JAD.

[5]  G. Wolf-Klein,et al.  Screening for Alzheimer's Disease by Clock Drawing , 1989, Journal of the American Geriatrics Society.

[6]  J. Miller,et al.  The clock drawing test is a poor screen for very mild dementia , 2002, Neurology.

[7]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[8]  D R Royall,et al.  Clock drawing is sensitive to executive control: a comparison of six methods. , 1999, The journals of gerontology. Series B, Psychological sciences and social sciences.

[9]  K. Shulman Clock‐drawing: is it the ideal cognitive screening test? , 2000, International journal of geriatric psychiatry.

[10]  Harald Hampel,et al.  CSF total tau, Aβ42 and phosphorylated tau protein as biomarkers for Alzheimer’s disease , 2001, Molecular Neurobiology.

[11]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[12]  E. Tobinick,et al.  Tumour Necrosis Factor Modulation for Treatment of Alzheimer’s Disease , 2009, CNS drugs.

[13]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[14]  Q. Jiang,et al.  Cell biology of IL-7, a key lymphotrophin. , 2005, Cytokine & growth factor reviews.