Moderate Alcohol Consumption Decreasing the Risk of Alzheimer’s Disease…
Moderate Alcohol Consumption Decreasing the Risk of Alzheimer’s Disease
What is known
Proposals for treatments that could slow down the progression of AD and easing the symptoms, mostly focusing on drugs ie. Donepezil
Main characteristics of AD and their basic biological underpinnings: amyloid, tangles, inflammation, loss of neuronal connections, cell death, neurotransmitter/cholinergic deficiency, neuronal mitochondrial damage
No cure: focus on improving the quality of life
recently, the focus shifted towards early prevention of AD
amyloid B aggregation research
incorporation of lifestyle factors: physical activity, cognitive training
when it comes to diet, small links to meditterean diet but not strong enough for recommendation (also vitamin B12 and folic acid supplements) → proposing consumption of antioxidants ie. Vitamin E and beta carotene --> antioxidant therapy
speculations that Other antioxidants ie. Polyphenols might be beneficial -> found in wine (reduce inflammation and improve waste removal (glymphatic system)
neuroprotective effects in both in vitro and in vivo preclinical models of AD
What is not known
the above-mentioned questions could not be decisively answered due to the following research limitations:
mixing diverse populations into one study ie. Classifying non-drinkers as people who have given up alcohol consumption due to health reasons (previous alcoholics) and lifetime non-drinkers
not considering major confounders ie. tabacco use, stress
The benefits are described based on memory and other cognitive tests, so the biological processes are not well described
Commenges et al. (2000) have shown that a diet rich in flavonoids was associated with a lower risk of dementia. In addition, the association with wine consumption disappeared after controlling for diet and may indicate that wine is a marker of a healthier diet.
why and how does moderate wine consumption benefit the brain?
is there a causal link?
only wine consumption or also other alcoholic beverages?
still inconclusive results concerning dietary recommendations for AD prevention, also controversive since current research proposes that moderate alcohol consumption could be beneficial
progressive, neurodegenerative, above 60 years of age
memory complaints, deterioration of ADLs
What should be done in the future:
studying more diverse populations
more diverse methods
examining drinking habits across the whole lifetime
take into account gender and genetic subtypes
Innovative nature of the study
looking into more alcoholic beverages in addition to wine ie. wine, beer, hard liquor ie. vodka
most of the studies use rat or mice AD models but there are fewer human clinical trials, limited clinical trial evidence
What do you want to do?
Taking into account the aforementioned research on AD and its limitations, the current research proposal deals with the following research question: Does moderate alcohol consumption prevent the development of AD?
Why is that problem important:
one of the most predominant causes of death (6th leading cause of death in US)
the most common dementia type among older individuals
Without advances in therapy, the number of symptomatic cases in the United States is predicted to rise to 13.2 million by 2050
since there is currently no cure for AD and major pharmaceutical companies withdraw from further reasearch on the development of the cure, the only alternative for managing AD is prevention based on life style factors, including alcohol consumption
What do you expect? (Hypotheses)
1: Alcohol in general: when considered together, there is a general benefit of moderate alcohol consumption
2: Wine: as a rich source of polyphenols, would be protective and would delay the onset of Alzheimer’s disease, wine most effective
3: Beer & liquor would not differ in term of their effectiveness.
data collection procedures
sampling: subjects age 60 with a probable AD diagnosis
research design: randomized control trial, double blind, 104 weeks (two years), clinical trial
description of population
appropriate method for research question?
pharmacokinetics in a smaller sample of randomly chosen participants
placebo, wine/resveratrol: 500mg daily, beer:...
5 fl oz of table wine at around 12 percent alcohol, 12 ounces beer, 1.5 ounces hard liquor
biomarker analysis at baseline, after 6, 12 months and after two years
MRI) to measure rate of whole-brain and regional atrophy at baseline, after 6 months, 12 months, after 2 years
Screening comprises of medical history, physical exam, neurological exam, and a MMSE.
reduced fluorodeoxyglucose (FDG) PET measurements of the cerebral metabolic rate for glucose (CMRgl) in brain regions preferentially affected by AD
structural MRI measurements of brain shrinkage (i.e., hippocampal, entorhinal cortex and whole brain volume loss, ventricular enlargement and gray matter loss and cortical thinning in regions preferentially affected by AD
PET measurements of fibrillar Aβ burden (using 11C-labeled Pittsburgh Compound-B
CSF analytes (i.e., low CSF Aβ42 levels, high t- or p-tau levels, or a combination of low Aβ42 and high t-tau or p-tau levels)
neurogranin as biomarker
indices of memory, executive, and visuospatial function
Time plan: 2 years
how will the research findings be used
proposing new public policies
public health model
better opportunities for presymptomatic AD treatment --> if the amyloid-β (Aβ) peptide plays a critical role in the final common pathway associated with the predisposition to AD, and if a treatment now in development targets the right form of Aβ and is started sufficiently early, it may be possible to prevent symptomatic AD completely
The main element favoring wine lies in its flavonoid content and its antioxidant activity
inhibit reactive oxygen species (ROS)-mediated cell death
polyphenols dose-dependently inhibit Aβ fibrilization
polyphenols inhibit Aβ aggregation