Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease

• Published in: Neurobiology of aging Vol. 30; no. 2; pp. 165 - 173
• Main Authors: Hansson, Oskar, Buchhave, Peder, Zetterberg, Henrik, Blennow, Kaj, Minthon, Lennart, Warkentin, Siegbert
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.02.2009; Elsevier
• Subjects: 80 and over; Aged; Aged, 80 and over; Alzheimer Disease; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Protein; Beta-amyloid; Biological and medical sciences; Biomarkers; Blood Flow Velocity; Cerebrospinal fluid; Cerebrovascular Circulation; Clinical Medicine; Cognition Disorders; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - diagnosis; Development. Senescence. Regeneration. Transplantation; diagnosis; Disease Progression; Female; Fundamental and applied biological sciences. Psychology; Geriatrics; Humans; Internal Medicine; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Mild cognitive impairment; Neurologi; Neurology; Peptide Fragments; Peptide Fragments - cerebrospinal fluid; Prognosis; Psychiatry; Psychology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psykiatri; Psykologi; Regional cerebral blood flow; Reproducibility of Results; Sensitivity and Specificity; Tau; tau Proteins; tau Proteins - cerebrospinal fluid; Vertebrates: nervous system and sense organs; Mild cognitive impairment; Beta-amyloid; Biomarkers; Tau; Regional cerebral blood flow; Cerebrospinal fluid; Alzheimer's disease; Regional blood flow; Nervous system diseases; Senescence; Alzheimer disease; Central nervous system; Biological marker; Cerebral disorder; Encephalon; Tau protein; β Amyloid protein; Central nervous system disease; Degenerative disease; mild cognitive impairment; Hemodynamics
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2007.06.009

Abstract This study aimed to identify preclinical Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) using measurements of both regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) biomarkers. Baseline rCBF assessments (133 Xe method) were performed in 70 patients with MCI who were cognitively stable for 4–6 years, 69 patients with MCI who subsequently developed AD, and 33 healthy individuals. CSF was collected at baseline and analyzed for β-amyloid1–42 , total tau and phophorylated tau. In contrast to patients with stable MCI, those who subsequently developed AD had decreased rCBF in the temporo-parietal cortex already at baseline. The relative risk of future progression to AD was particularly increased in MCI patients with decreased rCBF in parietal cortex (hazard ratio 3.1, P < 0.0001). Subjects with pathological levels of both CSF tau and β-amyloid1–42 were also at high risk of developing AD (hazard ratio 13.4, P < 0.0001). The MCI patients with a combination of decreased parietal rCBF and pathological CSF biomarkers at baseline had a substantially increased risk of future development of AD, with a hazard ratio of 24.3 ( P < 0.0001), when compared to those with normal CSF biomarkers. Moreover, decreased parietal rCBF (but not CSF biomarkers) was associated with a more rapid progression to AD. In conclusion, the combination of rCBF and CSF biomarkers improves the risk assessment of progression to AD in patients with MCI.