Coffee (and caffeine)

Introduction

Much evidence exists that coffee consumption, and caffeine in general (tea will be considered separately), seems to offer some protection against many forms of dementia, including Alzheimer's, regardless of ApoE status.

Effectiveness

Possibly somewhat preventive (applies to both Alzheimer’s and Parkinson’s), especially in women; possibly even slightly effective as a treatment.

Evidence

- Neuroprotective effects in several studies in mouse models of Alzheimer’s

PubMed ID:19581722

PubMed ID:19581723

PubMed ID:16938404

PubMed ID:12711619 (free full text available)

- Epidemiological studies.

PubMed ID:20859800 (Review)

PubMed ID:20182036 (2010. Effect seen in women, not in men.)

PubMed ID:17679672 (2007. Effect seen in women, not in men.)

PubMed ID:20164564 (2010. No effect seen in men.)

But many studies note effects in both men and women. See issue dedicated to caffeine and neurological effects for more studies:

Journal of Alzheimer's Disease, Volume 20, Supplement 1/2010.

Preface has good summary: "Therapeutic Opportunities for Caffeine in Alzheimer's Disease and Other Neurodegenerative Disorders".

Men smoke more, and smoking lowers caffeine levels: less effect in men because smoking not controlled for? (See “Caffeine intake and dementia: systematic review and meta-analysis”, p. S202 PubMed ID:20182026).

Large (4,809 subjects), recent (2011) analysis showed no consistent effects in men, but some (non-linear) effects in women. "Gender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study". PubMed ID:21841254

Proposed mechanism(s)

- Reduces presenilin 1 (PS1) and beta-secretase (BACE) activity. (www.ncbi.nlm.nih.gov/pmc/articles/PMC3205506/, “Caffeine”)

- Upregulation of adenosine A1 receptors which suppresses the synthesis of pro-inflammatory cytokines and reduced glutamate release and subsequent excitotoxic injury. (“Stuck at the bench: Potential natural neuroprotective compounds for concussion”, “Caffeine”; Caffeine may block inflammation linked to mild cognitive impairment)

- Adenosine associated decreases in blood brain barrier permeability may reduce the amount of amyloid passing into the brain? ("Caffeine, cognitive functioning, and white matter lesions in the elderly: establishing causality from epidemiological evidence", “Discussion”)

For more see “Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-Based CAIDE Study”, p. 89, “Possible mechanisms”.

Might APOE status affect relevance of the research supporting this intervention?

- Has any research examined ApoE status?

Two studies:

1. “Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-Based CAIDE Study” PubMed ID:19158424 concludes that carriers of APOE-ε4 (no differentiation here between hetero- and homozygotes) may receive more benefit in reduction in dementia risk (though not AD per se).

2. “Tea consumption and cognitive impairment and decline in older Chinese adults” PubMed ID:18614745 found no stratification of effect based on ε4 status.

Speculation about how it might or might not apply APOE-ε4 carriers

No reason to think the research wouldn’t apply to APOE-ε4 hetero- or homozygotes, though it might help ε4 carriers more than others, given that blood-brain barrier permeability seems to be greater in ε4 carriers, and reducing BBB permeability is one possible mechanism for caffeine’s effects.

Theoretical concerns?

- Caffeine raises homocysteine levels, and homocysteine is associated with greater risk of Alzheimer’s.

- Unfiltered coffee raises cholesterol levels somewhat.

- In a 2017 review "Does coffee consumption alter plasma lipoprotein(A) concentrations? A systematic review," unfiltered coffee was associated with mixed results in small controlled trials but raised Lp(a) somewhat in a larger cross-sectional study: "We identified six relevant publications describing nine experimental trials of various designs. There were a total of 640 participants across all studies and experimental groups. In short-term controlled studies, consumption of coffee, or coffee diterpenes was associated with either a reduction in serum Lp(a) of ≤11 mg/dl (6 trials, 275 participants), or no effect (2 trials, 56 participants). Conversely, one cross-sectional study with 309 participants showed serum Lp(a) was elevated in chronic consumers of boiled coffee who had a median Lp(a) of 13.0 mg/dl (range 0-130) compared with consumers of filtered coffee who had median Lp(a) 7.9 mg/dl (range 0-144) The effect of coffee on Lp(a) is complex and may follow a biphasic time-course. The type of coffee and the method of preparation appear to be important to determining the effect on Lp(a)." https://www.ncbi.nlm.nih.gov/pubmed/28084806