High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

Article type: Research Article

Authors: Cao, Chuanhai^{a; b; c; d; *} | Loewenstein, David A.^{e; f} | Lin, Xiaoyang^c | Zhang, Chi^c | Wang, Li^c | Duara, Ranjan^{e; f; g} | Wu, Yougui^h | Giannini, Alessandra^d | Bai, Geⁱ | Cai, Jianfengⁱ | Greig, Maria^e | Schofield, Elizabeth^e | Ashok, Raj^c | Small, Brent^j | Potter, Huntington^{c; k} | Arendash, Gary W.^{d; *}

Affiliations: [a] Department of Pharmaceutical Science, University of South Florida College of Pharmacy, Tampa, FL, USA | [b] Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL, USA | [c] USF Health Byrd Alzheimer's Institute, Tampa, FL, USA | [d] Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, USA | [e] Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, FL, USA | [f] Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA | [g] Department of Medicine and Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA | [h] Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL, USA | [i] Department of Chemistry, College of Arts and Science, University of South Florida, Tampa, FL, USA | [j] School of Aging Studies, College of Behavioral and Community Sciences, University of South Florida, Tampa, FL, USA | [k] Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL, USA

Correspondence: [*] Correspondence to: Chuanhai Cao, Ph.D., USF/Byrd Alzheimer's Institute, 4001 E. Fletcher Avenue, Tampa, FL 33613, USA. Tel.: +1 813 396 0711; Fax: +1 813 971 6478; E-mail: [email protected]. Gary W. Arendash, Ph.D., Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA. Tel.: +1 813 732 9040; Fax: +1 813 974 1614; Email: [email protected].

Abstract: Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer's disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 μM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI.

Keywords: Alzheimer's disease, caffeine, coffee, dementia, immune response, mild cognitive impairment, plasma cytokines

DOI: 10.3233/JAD-2012-111781

Journal: Journal of Alzheimer's Disease, vol. 30, no. 3, pp. 559-572, 2012