Science AMA Series: I’m Albert Hofman, Chair of the Department of Epidemiology at Harvard T.H. Chan School of Public Health and the Stephen B. Kay Family Professor of Public Health and Clinical Epidemiology, and I’m here to talk about Alzheimer’s disease. Ask me anything!

Abstract

Hi, reddit! I’m Albert Hofman, Chair of the Department of Epidemiology at Harvard T.H. Chan School of Public Health. I study the epidemiology of common neurologic and vascular diseases, in particular dementia and stroke. I have initiated and served as the principal investigator for two population-based, prospective cohort studies (the Rotterdam Study and the Generation R Study examining neurological, cardiovascular, and endocrine diseases. These studies harnessed new epidemiological tools, including the genome-wide assessment and large-scale imaging of whole cohorts, enabling researchers to study the interrelations of those diseases and their development.

According to the 2015 World Alzheimer Report, 46 million people worldwide are living with dementia—a number that is expected to triple by 2050. While those statistics are sobering, there is reason for optimism. Research has shown us that vascular factors are important causes of dementia and Alzheimer’s, and the good news is that these vascular factors can be influenced. You can do something about your risk for vascular diseases, by treating high blood pressure or high cholesterol, or by not smoking. We have actually seen a gradual decline in the incidence of dementia over the past decade, and I think it is because of those kinds of preventative interventions. There will be more people having dementia as they become older, because the population of older people in the world is increasing—but the incidence of dementia is not. Overall, the picture for Alzheimer’s is improving.

EDIT: It's 11:17 AM ET and I'm going to get started. Thanks for all the great questions so far!

EDIT 2: It's 1:05 PM ET and I do have to go now. Thank you for all your great questions. I'd love to come back and do this again!

My grandmother suffered from Dementia and Alzheimer's, and her son, my father, is starting to lose his memory more and more. It's to the point where we are thinking of finding a way of intervening with his doctor to ask for tests to he run.

Anyway, what can I do at 31 to sustain my brain? I don't know if that's the correct verbiage, but I'm wanting to know what I can do to keep this disease at bay for my own life. My cholesterol and blood pressure levels are low and I've never smoked, if that helps.

born_mystery

Thank you born_mystery for your great question. First of all, you are not alone. Dementia and Alzheimer disease is unfortunately very frequent in the elderly. It goes up from about 1% in those aged 65 to at least 35% in those aged 95. The best way to try prevent dementia is to take measures to prevent heart disease and stroke, i.e., do not smoke, have regular physical activity, have low blood pressure and cholesterol (as you mentioned). These preventive measures cannot start too early, so at 31 please continue with these preventive measures.


Thanks so much for offering this AMA! My grandfather currently is suffering from Alzheimer's- and it is definitely in the severe stage by now.

I have many questions, but I'll stick to one- what are the best ways to meaningfully connect with loved ones suffering from Alzheimer's disease? I ask this because- and I know this may sound rude- everytime I am with him I find it a little uncomfortable/awkward because I can't hold a conversation with him anymore, and therefore I'm not sure how to best interact.

I used to be very close with him and I'd like to still have a relationship with him, and make the most of this terrible situation.

Thanks again! I look forward to hearing your answers here.

clemthecat

Dear clemthecat, thank you for your question. I think I know how you feel, my grandfather and father suffered from dementia. I think you do best to simply be with him. You may ask nurses who care for dementia patients to give you specific advice, but be around him at times, perhaps bring some food or drink if possible, will help him (and you).


Have you ever taken LSD and how do you feel sharing the same name with the scientist who discovered its effects? More serious question: do you think psychedelics have any medical use in combating, if not Alzheimer's, but any other neurodegenerative disease? Especially something like depression?

MpMerv

Dear MpMerv, no LSD for me, but I have known Albert Hoffmann (slightly differently spelled name though...). I doubt that psychedelic drugs can have a sustained beneficial role, but this is not my field. Please ask your psychiatrist.


What do you think of GPS devices on those with dementia so they can still be independent and go out but family can be assured of their whereabouts?

hellangel_

Dear hellangel, these devices can be helpful particularly in early stages of dementia.


From what I've learned (a few years back), prions are suspected to be the cause of Alzheimer's, how do the cardiovascular risk factors contribute to the development of the disease?

WedgeTurn

Dear WedgeTurn, indeed, prions have been proposed as a possible cause of dementia (like in the human form of mad cow disease, Creutfeldt-Jakob disease). There is actually no evidence that prions lead to Alzheimer disease itself. Cardiovascular risk factors indeed contribute to the development of dementia and Alzheimer disease. It can be through chronic lack of blood (due to atheriosclerosis, particularly of the small blood vessels in the brain), so called chronic hypo-perfusion, or through the effect on amyloid, leading to deposits in the brain. This cardiovascular link is important in that it is currently the only known way to help prevent the disease.


Hi Albert, and thank you for doing this AMA.

It has been another rough year for clinical trials aimed at treating Alzheimer's disease. The two most prominent failures in my mind were MRK's BACE inhibitor and LLY's abeta antibody. The BACE inhibitor fail was particularly troubling, because we know this drug was both potent and on-target.

How are you interpreting the results of these studies? Is the notion that abeta is broadly pathological across non-familial AD starting to be in doubt in your mind? If not, would a BACE inhibitor failure in the prodromal population cause you to re-think?

SirT6

Dear SirT6, thank you for your comment. Indeed, the Alzheimer amyloid trials have not been successful until now. There are two lines of explanation for this: (1) the trials were too small and too late, and (2) amyloid is a product, not a cause, of Alzheimer. I hope for explanation (1) and therefore more and bigger trials are needed, but I fear that explanation (2) may be correct. A BACE inhibitor trial in the prodromal phase may even be too late...


My grandfather had Alzheimer's and it was devastating to see how it affected him. His son, my father, has done DNA testing through a popular service and it suggested that he has a very low chance of developing the disease. Do you know much about these tests and their reliability? Are there any true methods of being able to predict who might develop Alzheimer's?

lolly-doll

Dear lolly-doll, thank you for your question. Genetic factors are certainly involved in Alzheimer, we know about 40 genes that are involved, but their individual effects are very, very small. We cannot reasonably predict the occurrence of Alzheimer on the basis of genetic tests.


I work in the senior living industry and deal with dementia and Alzheimer's daily. I also was in home health for a few years. If it has been proven that music can help bring back some memories and really soothe the person with Alzheimer's, how come it hasn't been utilized more?

rquay122

Dear rquay122, music studies are not my area but I support your view. Certainly soothing and perhaps even bringing back some memories. In another field: there is increasing evidence of improved outcome of major surgery when music is played (for the patient) during the operation...


What are emerging technologies' roles in learning about and fighting against Alzheimer's?

Thank you.

kingdot

Dear kingdot, new imaging technologies (MRI, PET) are tremendously important in studying Alzheimer's because it allows us to see changes in the brain over time and study its possible causes. Genomic technologies have helped us find a relatively large number of genes implicated in the disease, and hopefully these may also yield future clues to prevention and treatment.


If we lived long enough would all humans get Alzheimer's eventually?

asp2_downhill

Dear asp2_downhill, this is a key epidemiological question, and I do not know the answer. All I can say is that if you look at those aged 95-100 over half is diagnosed with dementia; and if you look at the incidence of the disease (new cases) by age, it keeps going up, and there is no evidence of the incidence leveling off. This may point at specific causes of the disease being frequent and working over a long time.


What environmental items, if any, have been conclusively linked to Alzheimer's? I've read of allergy pills recently, cooking in aluminum foil, deodorant...

Thank you for taking the time to answer questions. Having seen my grandfather and mother-in-law go through this awful disease, I want to skew the odds in my favor if I can. Perhaps the damage is done....

modestexhibitionist

Dear modestexhibitionist, I am not aware of any environmental causes that are conclusively linked to Alzheimer. Your best bet is prevention though cardiovascular risk factors (see earlier response to /u/born_mystery).


Hello, thank you for your time. My grandmother had Alzheimer's disease, and I'm worried about my own genetic susceptibility.

What do you think about genetic testing for Alzheimer's-related genes? Is this something you would recommend to those with a family history? Thanks!

aprendemos

Dear aprendemos, no I would not recommend genetic testing. (1) the tests are not good, and (2) a test result does not have any specific recommended action.


Hello Dr. Hofman,

What does a competitive applicant for a research assistant position to your research group, who holds at least a bachelor's degree, look like? Understandably, biology related majors would be the most competitive, but how do psychology majors fare? How does having a biology and/or neuro minor change the competitiveness of psychology majors? Do you expect applicants to have an undergraduate thesis, a publication, presented at a conference, ECT.? How many years of research experience would the competitive applicant have for biology/ premed majors? Psychology majors?

How involved are the responsibilities of an undergraduate student RA and a recent graduate RA?

Thank you for your time.

fallingsaucer

You can send me an email at ahofman@hsph.harvard.edu, and I will refer you to relevant colleagues.


I work with seniors, many of whom are developing dementia and Alzheimer's, and am constantly seeing claims that this or that will help delay or prevent the conditions (meditation, doing puzzles, dietary changes...). Some of these seem to have been debunked, though.

What, if any, activities or behaviors do you think have legitimately been shown to help slow or prevent the conditions (other than treating blood pressure, cholesterol, and smoking)?

Cogitotoro

Dear Cogitotoro, I do not know of any medication that in the longer term delays or prevents Alzheimer. There is of course the idea of 'use it or lose it' and this may perhaps delay Alzheimer, or at least its diagnosis, in the short term.


Why do you expect the population with dementia to triple?

justmeliving

Dear justmeliving, thank you for your question. This is because we live longer. Every 4 years we add one year to life (in most countries). So we get more really old people who have a high risk of dementia. We are, in other words, the victims of our own success in increasing life expectancy. The increase in dementia is not because the incidence rate (new cases) of the disease increase: on the contrary there is quite some evidence that the dementia incidence has declined in the past decade (evidence first from European studies, and more recently also for US studies). I think the latter is because of better prevention and treatment of cardiovascular diseases.


Maybe not your area specifically, but I look after my mum's care needs and she is in the early to moderate stages of Alzheimer's. Along with memory issues and other stuff, she accuses people of stealing things that she misplaced. I can usually find them so that's ok but what is the best strategy to deal with this when the person isn't so far along that distracting them will work? It cripples her with sadness that people she thought she could trust would steal from her and because of the emotional impact of that she remembers the apparent thefts (often forgetting that I found the missing item). She's on appropriate medication for this, prescribed by her geriatrician, so I'm curious about strategies I can employ beyond attempting to reason with the diminishing capacity she has to reason things through.

Edit. Just adding she lives in an supported but independent living apartment with carers who come and go a few times per week so trusted people regularly see her, along with family, hence the potential for theft in her mind.

onebridge

Dear onebridge, thank you for your question which I empathize with from own experience. I have found much support in experienced nurses who care for Alzheimer patients. Perhaps ask them, you may be surprised about their suggestions.

This brings out an old and very important and theme for medicine at large: sometimes prevent, sometimes cure, but always care.


My father suffered with Alzheimers - thank you very much for your good work. I have often wondered about synergistic effects from new chemical compounds in the environment. Has anyone made a graph showing the introduction of synthetic chemicals into the public space (such as fragrances, plastics, carpeting, etc) over the past 200 years, and then superimposed a plot of the incidence of diseases such as Alzheimer's?

cosmotravella

Dear cosmotravella, I am not aware of evidence for environmental chemicals as a cause of Alzheimer.


I oftentimes don't get as much sleep as I need to. Is there any correlation between chronic lack of sleep and the development of alzhiemers?

ShiitakeTheMushroom

Dear ShiitakeTheMushroom, I don't think so.


I've heard that amyloid plaques are a result of alpha amyloidin changing from mostly helical to mostly sheet confirmation. Can this conformational change be autocatalytic, can one aberrant protein cause surrounding amyloidin molecules to change or is this a problem of chaperones or folding mechanisms post translation?

Also does marijuana have any effect on plaques?

Thank you.

jabanobotha

I've heard that amyloid plaques are a result of alpha amyloidin changing from mostly helical to mostly sheet confirmation. Can this conformational change be autocatalytic, can one aberrant protein cause surrounding amyloidin molecules to change or is this a problem of chaperones or folding mechanisms post translation?

Great question, my compliments

Also does marijuana have any effect on plaques?

I don't fully know, but I don't think so


As a neuroepidemiologist what would you say are the most important diseases that need further research? What skills do you use on a day to day basis?

luxurianttranquil

Dear luxurianttranquil, I think it is fair to say that nearly all neurological diseases need further research - this is the same as saying that in many neurological diseases we do not know the causes, just as examples, Alzheimer, Parkinson, ALS.


What is the correlation between concussions and early onset Alzheimer's?

seprehab

Dear seprehab, there is a longstanding view that head trauma may cause dementia (see dementia pugilistica), but the evidence for it is scant. A head trauma is likely to have the diagnosis of (early) Alzheimer made, rather than cause the disease.


What is the best way to prevent Alzheimer's Disease?

Transkar

Dear Transkar: cardiovascular prevention.


Many non demented older adults show beta analysis buildup and lots of tau tangles upon autopsy, but show very little cognitive symptioms. How do you think that amaloid and tau tangles react with other conditions like vascular stress to cause cognitive issues?

GetTheeAShrubbery

Dear GetTheeAShrubbery, great question, and a real focus of current research. I do not (yet) know the answer but I feel that the interplay of vascular factors with amyloid/tau (combination) is key.


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