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A new study shows that patients with mild cognitive impairment (MCI) do not progress to dementia if they drink enough coffee! Gotta love it. I'm going to start drinking a whole pot, by golly. The researchers in this study think that it's the caffeine, and not the anti-oxidants, that has the anti-dementia effect, but according to mouse studies, it has to be coffee. Those patients with a little MCI who java it up enough to have a plasma caffeine level of 1200ng/mL did not go into dementia. 100%. The caffeine appears to inhibit an enzyme used in the manufacture of beta amyloid! They're also tracking cytokines in the plasma and finding that there's a particular profile assorted with conversion to Alzheimer's disease (low IL-6, IL-10, and G-CSF). In the future we might consider testing for those cytokines to detect impending dementia in healthy patients.

Dr Arendash
June issue of the Journal of Alzheimer's Disease.
case-control study
2 cohorts of 124 participants in a Florida Alzheimer's Disease Research Center
aged 65 years and older
categorized at baseline based on neurologic assessments and cognitive tests, plus serum tests
normal, MCI, or dementia
2-4 years duration

annual reassessments
categorized into five groups:
(1) initially normal and remained normal
(2) initially normal but converted to MCI
(3) initially MCI and remained so
(4) initially MCI but converted to dementia
(5) initially dementia and remained so

CAFFEINE LEVELS
initial plasma caffeine levels in participants with MCI relative lower than normal group
also lower in participants with dementia than in normals, but not statistically sig
26% lower plasma level of caffeine in normal persons who converted to MCI during study
also not statistically sig dt wide variability in levels
11 patients with MCI-->dementia had plasma caffeine levels 51% below initial (vs MCI-->MCI)

No MCI-->dementia participants had initial levels above 1200 ng/mL
half of those with stable MCI had higher levels
Baseline caff >1200 ng/mL in MCI patients associated with 100% chance of avoiding dementia during 2-4-year follow-up.

Patients with MCI in both the Miami (n = 81) and the Tampa (n = 43) study cohorts independently showed the same relationship between blood caffeine levels and later risk for dementia progression.

Important threshhold: 1200-ng/mL
to get there must drink 3-5 cups/d
target of 5 cups or 500 mg of caffeine

previous AD mouse studies
1 to 2 cups (between 100 and 200 mg of caffeine)
was not enough to ward off dementia
not known if need to space out cups or OK to drink all in morning

other factors matter
50% of patients w MCI w caff below 1200 ng/mL also didn't progress to dementia
cognitive and physical activity
presence of hypertension
antioxidant intake: fruits and vegetables

CYTOKINES!
3 cytokines lower in pts who convert to AD than in stable MCI AND pts already with dementia
granulocyte colony-stimulating factors
(G-CSF or in my older notes, GM-CSF for granulocyte monocyte CSF)
interleukin-10
interleukin-6
None of the 8 other plasma cytokines that were measured showed any such profile when the same 2 MCI subgroups were compared.
this could indicate impending AD!

MICE
also make beta amyloid
long-term oral caffeine prevents cognitive impair in them too
cytokine profile in mice same as in humans
other sources of caffeine don't work the same

CAFFEINE
suppresses brain levels of enzymes required for amyloid-beta production
targetS of specific signal transduction mechanisms
MB something in coffee increases plasma levels of those 3 key cytokines: G-CSF, interleukin-10, and interleukin-6
G-CSF has esp beneficial cognitive actions in AD mice: synaptogenesis and neurogenesis

retrospective analysis

theory: less coffee consumption may relate to other things that influence dementia
ie HTN, dep, CV dz, less social activity

Still, one of Dr. Ritchie's own previous studies, published in Neurology , concluded that the psychostimulant properties of caffeine appear to reduce cognitive decline in women without dementia, especially at higher ages.

J Alzheimer Dis. 2012;30:559-572. Abstract
http://www.j-alz.com/issues/30/vol30-3.html
Pages 559-572
Chuanhai Cao, David A. Loewenstein, Xiaoyang Lin, Chi Zhang, Li Wang, Ranjan Duara, Yougui Wu, Alessandra Giannini, Ge Bai, Jianfeng Cai, Maria Greig, Elizabeth Schofield, Raj Ashok, Brent Small, Huntington Potter, Gary W. Arendash
High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia
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.

SOURCES
http://www.medscape.com/viewarticle/765781?src=mpnews&spon=34
http://www.j-alz.com/issues/30/vol30-3.html

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