Alzheimer's: Another clue

Given that depression and anxiety have been categorized as "the common colds of mental health," this news about Alzheimer's is quite frankly terrifying. As one of the millions of people who have fought a lifelong struggle with anxiety, stress, panic attacks and some degree of depression while going to work every day and trying hard to carry on, this sounds like just one more kick in the teeth that makes me wonder what the hell good all the struggling will have done. If, at the end of the day, working to overcome these handicaps and win back one's personality from the hell of anxiety and depression only results in losing it to Alzheimer's, what is the point?

It would help to have some context. If suffering from anxiety and depression increases one's risk of AD by a certain percentage, is there some way to frame that percentage in terms that seem less hopleless? If, for example, 1 in 10 people will get AD, an increase x 4 would mean 4 chances in 10, not good but still not a guarantee that you will develop it.

I have long said that the fearsome day I am diagnosed with AD is in fact going to be the day before the last day of my life. This further depressing news only hardens that belief. Frankly, the future looks a bit bleak.

Mark S., Illinois

My husband was diagnosed with bipolar disorder in his early 50's. The illness was not properly treated, and he was hospitalized for a severe manic episode 4 years ago. Since that time he has suffered from severe depression and experienced increasing memory and cognitive difficulties. His psychiatrist attributed these symptoms to depression until about six months ago. After a battery of tests ranging from lumbar puncture to PET/CT scan, my husband has been diagnosed with Alzheimer's disease. He is only 60 years old!

When we heard Dr. Gupta's report this morning we were both stunned. There is so much that we don't know about the brain. I can only hope that research will bring more understanding and treatment for the diseases that have afflicted my husband.

Patty B
New York

Hi Sunjay,

What about some of the new research initiatives regarding omega-3 fatty acids and effects on brain lipids? Some of these research is really facinating, and I would bet an interesting topic for discussion on your Saturday morning program. Very neat anti-inflammatory ties.

Yes, I know 1 alzheimer's patient. She passed a few years ago. In her 80's. Although only seeing her sporadically over 37 years, I had never known her to be depressed. An outging,hardworking,energetic woman, she always appeared well. I know she had medical problems most of her adult life. Could medications over long periods contribute to the disease; sideaffects resulting in alzheimers??

Dr. Gupta, you,a neurosurgeon; (someone who does surgery on the nervous system (especially the brain), with the complexities of the brain when trama strikes, whether by disease or injury, i am continually suprised more www networking is not done within your field; neurology. I am a West Nile Viral Encephalitis victim. One of many thousands affected directly from NEW RE-EMERGING INFECTIOUS DISEASES, should'nt alzheimer's qualify in this category?
I am curious, as most of the discriptives for alzheimers are the same for encephalitis. And not surpirsingly, they too are thrown into the depression bucket.
I am anxious for your reply, thank you, april
april@anindependantreview.org

other interesting reading and information http://www.inspire.com/groups/encephalitis-global/
http://www.encephalitis.info/
http://www.1halloween.net/encephalitis/index.html
http://www.westnilesurvivor.com/updating.html
these just to name a few. Again, I thank you for your time.

My husband was diagnosed with Alheimer's late last year. He is currently on Aricept – but with little if no success. In retrospect, there may have been signs that we ignored as just silly lapses or we were in complete denial. It wasn't that he forgot where he put the keys, etc..... he forgot what to do with items he had used for 60 years or how to do simple tasks or where he was. Found him in the yard one day looking at the lawnmower with no idea how to start it. Another time he couldn't remember his grandson's name. Called me at home on another occasion to tell me he couldn't remember where he was going. It is a sad disease that slowly takes away a persons dignity before oblivion takes hold. As a caregiver I find the stress of caring for him debilitating as well as depressing.

I have a mother with dementia (85) and growing up, I helped her care for her mother with dementia. All the women on that side of the family were very similar...all lived along time (to 100) but suffered from dementia. I never heard an Alzheimer's diagnosis. My mother's neurologist says there is a difference and that dementia does not always "turn into" Alzheimer's. She is still independent, but forgets very short term things (minute to minute, day to day events), but is perfectly able to live in her home and follow routines, and make decisions wisely, so far. She walks miles a day to keep herself busy. She has done crossword puzzles all her life, but does not now. My 11 year old daughter is now helping me care for her and I KNOW I will get it (i'm 45). I'm watching all the reports and am trying to prevent it at all costs, but I feel I'm doomed. My daughter and I have made a contract already about my care, NO MATTER what protests I make while in the throes of dementia. It's sad, but it's our legacy. That's what family is for.

love your blog!

I am currently in the depths of a theiss project on cortisol, and my advisor and I are both curious about your reference in relation to AD. In many depressed and axious people, serotonin levels are very high, (for those of you who like mechanisms) stimulating production of corticotropin- releasing hormone. This hormone, in addition to signaling for cortisol release, causes much of the anxiety and related symptoms associated with stress. Cortisol actually decreases the amount of this hormone that is produced, in order that this not be an unending cycle. In keeping with this, many people suffering from depression actually have seriously reduced cortisol production in response to seratonin and CRH signalling, so CRH remains very high, and making them very anxious.

I have seen several papers linking seratonin, depression and Alzheimer's. I would really like to see how high cortisol levels fit into this picture. Thank you.

Hello Dr. Gupta:
My mother had an stroke 8 years ago, and then after she was diagnosed with Alzheimer"s ,and today she is 86 years od and she has been diagnosed with Dementia. My oldest sister she is 65 year old and my brother is 64 yeras old, and aparently they are haven symtoms of Alzheimer's too, what can we do to help them?.
I understand that it is a medication that can help to slow the processes.
So Dr. Gupta this means that I will get that illneses too?.What can we do to stop this for happening on the rest of the family?. We are at lease 80 members on this family .

Thank you,
Aliria

I keep reading about experimental drugs that can stop or even reverse AD symptoms, like PBT2. Where are they and when will all the empty chin music stop and the actual application begin??????

http://news.bbc.co.uk/2/hi/health/5210048.stm

Mark S.

Dr. Gupta,
I have seen you on tv and know you are reputable so I feel able to share. My father,now 88, has been diagnosed with dementia but Alzheimer's is used interchangably. My family noted eight years ago that he seemed to fall asleep much easier than before. He would drive to a store only a block or less away and fall asleep in the parking lot. He used to drive alot but in 2000, we would catch him falling asleep at the wheel. Obviously, we intervened and his doctor convinced him to give up his license. It is then that the depression started and has gone downhill since. I am lucky to have my 91 year old mother still alive and mentally alert living with my dad in an assisted living home. I certainly hope a cure for this devastating disease is found soon because I don't believe this is the way we were ment to spend our last days on this earth. Thank you and your fellow professionals for your great work.

Dr. Gupta,

I absolutely think you are great. I find this report about depression potentially being a precursor to Alzheimer's terrifying. I have been treated for depression successfully with some of the newer SSRI medications. What if you were treated successfully as I was? Am I still at risk? What can you do if you are being treated for depression to lower your risk further?

Thanks, I am a huge fan here in Altanta.

There was an article posted on the BBC yesterday about a company in Houston that is about to launch a diagnostic test for Alzheimer's. Here is the link:

http://news.bbc.co.uk/2/hi/health/7330321.stm

The technology is based upon an analysis of protein biomarkers present in blood. Is this a realistic test for a definitive diagnosis?

Dr. Gupta,
I am a 68 year old woman diagnosed with depression when I was in my early 40's. I have to agree with Mark S. I, too, struggle daily with anxiety, stress and depression and yes, I am being treated for it. I've gone through several medicines before finding one that takes the edge off. Some days, it hardly seems worth the effort. I have thoughts of suicide but no plans...yet.
Hearing the news today that depression and stress may be linked to Alzheimer's disease was shattering. What is the sense of trying to live with depression if it only ends in Alzheimer's.
Maybe I'm grabbing at straws but 917 seems like a small number to test. And the fact that they were all Catholic might factor in. I grew up in the religion and I believe it was a factor in my illness. Please give me more information on the likelihood of my ending up with Alzheimer's. Again, I agress with Mark S. The future looks bleak indeed.

MY DAD HAS ALZHEIMERS TODAY, THE FIRST SIGN WAS DEPRESSION, DID NOT HAVE ANY INTEREST IN DOING ANYTHING HE USED TOO, WANTED NOT TO LIVE ANYMORE, HE BECAME MORE AND MORE DEPRESS, AND NOW HE IS IN A NURSING HOME. IT'S VERY SAD SITUATION SOME OF US ARE STILL IN DENIAL.

just wantedto say that my mother died in November 2007 at the age of
80 after having Alzheimer for about 5 years. I was going through a
horrible divorce at the time which caused much stress to my mother
along with depression. Even though my maternal grandmother
also died of this disease, your theory of cortisol makes a lot of
sense.
Needless to say, I think about this very often- I am 57.

MY DAD IS ALZHEIMERS, THE FIRST SIGN WAS DEPRESSION, FORGETFUL , NO INTEREST , NOT WANTED TO LIVE, BECAME DEPENDENT.

what about the connection between soy and Alzheimers? There is a study that showed men who ate soy had brain shrinkage and earlier onset of Alzheimers. Soy is not the miracle food that most people have been lead to believe.

My dearest friend was buried last week, alongside her husband. They died in a housefire – she had altzimhers – he tried to save her life- both 81 years of age. Iris did experience depression thu out her life – but was not treared for depression. She worried about everything – and was a very upbeat person, to friends and co-workers. No one knew how depressed she really was. She had back pain for years – took strong pain pills – I do believe depression/worry triggers this horrible disease.

Dr. Gupta-
For someone who has suffered with anxiety and depression most of my life this is absolutely terrifying news. I hope you have an expanded segment on your show this Saturday not only to discuss this study but put into perspective for those of us who have depression to avoid the FEAR this study brings to us.

I have read a few of my fellow bloggers statements that indicate they too struggle as to why continue the fight every day with a relentless disease of depression only to get Alzheimers. Also we need you to keep us posted on the latest treatments–medical or holistic–because I find relying on medical professionals to keep me informed does not work.

I continue to enjoy your perspectives and amazing diversity of work.

As people get older, the collective fear of developing Alzheimers goes up tremendously. With the internet, the kinds of questions people ask about how to avoid getting the disease are broad and never ending. Theories such as inflamation, and anatomic changes with age are hard to prove and few studies can be done to control for all the variables associated with aging. Yet the current research is exciting. If the link between cortisol and disease developement is true, we should see an even more dramatic rise in the disease given the amount of steroids used in modern medicine to modify disease. Steroids are used almost every day in an ever aging population. If this is true, the prevelance of Alzheimers should increase dramatically in the future.

Donna R. and Tina, apparently Dr. Gupta's pager is turned off.

Mark S.

This is the sad story of my spiritual friend's(I call her aunt) husband, who suffered for 7 years, of the rare form of the Alzheimer Disease called EOAD(early onset AD)before he passed away. This happened in India and he was a scientist at BARC(Baba Atomic Research Center) and he developed EOAD at the age of 45. The doctors diagnosed it as Alzheimers with a big question mark. Before the doctors said anything about his conditions, he, as a scientist, knew the symptoms of AD and duly resigned his job. The chief of the division was surprised as well as felt delicate(probably they noticed certain things in him) that he submitted his resignation before they could take any action. Since he was a very dedicated scientist(he didn't take a single sick leave also), without even his coming to work, they made arrangements for him and the family to receive monthly salary until his retirement age. The wife was not working and the two sons were still in school.

He forgot his own wife(it was a love marriage and must have been painful for the wife) and his two kids. But he would talk didn't suffer much from communication but at times the talk would be totally uncorrelated . He used to get angered a lot(one day he wanted to commit suicide and that's day the wife knew for sure that her husband is suffering from some grave illness). He would talk to one of her female colleagues nicely. So the wife would invite her female colleague so that it would make him happy. The first son, seeing father's sufferings, tortured his own health by not eating properly etc. As a result of the disruption of metabolism, he is now suffering from Type II Diabetes(it was worse, now he is doing better with appropriate food intake so that his blood glucose doesn't spike up and down erroneously). Anyways, the story is that my friend's husband died when he was 52! Now she is with her first son in US and both visited me last month. Only that time I came to know about her husband's conditions. My spiritual friend is a PhD in the indian language "Samskrt" and teaches to kids and adults for free. She has lot of westerner students also apart from Indian students in US.

EOAD accounts for 5-10% of all ADs. This is genetic and have identified different genes on different chromosomes(1,4 & 21). Even if one of the gene variant is inherited, the person will almost develop early-onset AD. It's a 50-50 chance of inheriting if one of the parents has it. That's why the inheritance pattern is called autosomal dominant inhertance.

There is late-onset AD which forms the majority of all AD cases and normally occurs around and after age 65. No specific gene has been identified to cause late-onset AD but some genetic factors seem to play a role in causing it. A protein called apolipoprotein(APOE) on chromosome 19(the same protein in the functioning of cholestrol) has been identified and it comes in 3 different forms(APOE-e2,APOE-e3,APOE-e4).

We inherit APOE from each parent. Inheriting 2 copies of allele e4 increases one's risk of getting late-onset AD. There are people, with two copies, who have not developed AD and are healthy also. That's why this is called a risk factor gene.

Albert Einstein: It is my view that the vegetarian manner of living would most beneficially influence mankind

What good is it to know if you're going to have Alzheimer's if there is nothing you can do about it? I can see value once a cause and cure are discovered.

My mother was one of the most positive, upbeat, personable people you would ever want to meet. Never a bad word about anyone, people loved to be around her, always cheerful. Now she has Alzheimer's. She is 81. Neither parent had this disease-they both had good health into their nineties. She alway said she had a bad memory, but we began to see the textbook symptoms of this awful disease in her a few years ago. While she is still cheerful with people, she can't remember their names, is never wrong about anything, people steal from her because she would never lose her purse, etc. I never saw any symptoms of depression in my mother. I still don't, even now that she is in assisted living, which we had to call her own apartment to get her to move there because she just knew she didn't need to go to an assisted living facility. She started out with Airicept and Namenda and is now on Namenda and Razadene. I really don't see any type of improvement in her or slowing down of the symptoms with this medication.

My Mother-in-law has alzheimers. She is 95 years old and was diagnosed years ago with depression. Looking back I would say that the earliest symptom, that I now know to look for, was difficulty with time and dates. She would be upset when we arrived an hour or two later that she expected us, even when we emphasized the time. She would also show up for Dr. appointments as much as a week early or late. The time issue started when she was about 75 and it progressed slowly to include appointments by the age of 80.

We live a long way from Mom and when she finally had to give up her independance at the age of 91, in her storage room we found boxes of notes that she had written that actually scripted conversations we had had with her for years. She had hidden her disease very well and yet was obviously painfully aware of it.

Mom is now, most days, living in a different world. It appears that on a day to day basis, my husband is around 2 or 3 and yet, when we talk to her for a few minutes, she knows who we are. She is extremely healthy and it is sad that she no longer knows she has grandchildren and great-grandchildren.

http://news.bbc.co.uk/2/hi/health/1668932.stm

This 2001 BBC article and many other articles say to eat lots of tumeric (curry) if you want to ward off alzheimers.

Tumeric is one of the few things in the world that penetrates the blood brain barrier and has also been attributed to the extremely low rates of MS in India.

Hello to all,

My mother passed away at the age of 74 in 2004.
My mother was a passive person and she seemed easygoing.
Toward the end of her life while she was still able to talk coherently, she once made this comment when asked why she didn't speak up much...."I don't really have anything to say that anyone would want to hear." She really didn't have a very good image of herself. She was the youngest of 10 farmer children in depression era Kansas. Because their were so many children their mother was weakened by the time my mother (the last of ten) was born. As a result, mom was raised by older siblings and passed around to different one's at times.
She married two alcholics in her life and things were stressful as a result.
She began to show signs of forgetfulness as early as age 45.
It was kind of a joke in our family. Dad would tease her and say
"It's the mind that goes first"
When I was 15 I went to my dad and told him I thought things were getting worse. Having had to guide my mom while driving since I was 6 or 7 and having to help mom find the car in the parking lot was a regular and accepted thing. But since I'd seen it for so long it was obvious to me that things were getting worse. Dad had seen it too so we took mom to the Dr. He said that there wasn't too much info on what he called "Early Onset Demenita" and that early reports suggested that more oxygen to the brain would be helpful.
Mom began to ride for charities on her bike. She took several awards for riding 100 miles a day for several days on end. Dad served as the helpmate. Following along in the car and giving mom support.
Sure the extra activity could not have been bad but you know, now that I've read Dr. Gupta's comments, I believe that this was the happiest time in my mother life. She was doing something helpful (she loved that) Dad was supporting her (she finally felt special for the first time in her life) and this helped her maintain her independent lifestyle for about another 20 years. Once she could not long ride a bike she did aerobic workouts. But eventually dad died from his years of alcoholism and mom was not able to function well from that point on.
I see the correlation between moms lifelong battle with being happy. She always tried to accept her circumstances but at what price?
I think this is a good lesson for me. Find joy in my life and embrace it!
Warm Regards and special thoughts to all of you who have had close contact with this disease.
Robyn

My mother, age 27 in 1952 – hospitalized for depresssion – rec'd shock treatments – diagnosed through the years with multiple illnesses including arthritis, fibromyalgia, 3 back surgeries, ulcers and esophageal problems (3 stomach surgeries), extremely sedentary and a constant diet of processed foods high in fat content – is now 83 in a nursing home with Alzheimers. We thought the multiple surgeries and anesthesia were causing the dementia, which may have added, but I think the depression and lack of activity is the real culprit.

Dr. Gupta-

My mother passed away in 2003 with Breast Cancer and Alzheimer's (the cancer is what really ended her life). My brother and I decided to have an autopsy completed to confirm the Alzheimer's diagnosis. The University of Florida performed the analysis and it was determined that yes, it was Alzheimer's and secondarily, it was the worst case of Alzheimer's seen in a person so young (age 61). The plaques in her brain began in the center and were working their way outward. It's very hard to know which started first. . .the cancer or the Alzheimer's. Initially, she had trouble writing (easily explained by the doctors as tendonitis), then she would miss letters (lve, Mom) and then she would miss words while speaking. She never exhibited emotional swings (in fact she got very passive instead) and eventually became non-verbal because the words just wouldn't come. I have the full report from the doctor who performed the brain analysis if you're interested in a copy. There seems to be a large link between cancer and dementia. The question is - which came first and does one contribute to the other??

According to a study published in the journal Neuroepidemiology, 12:28-36, 1993, subjects who ate meat, including poultry and fish, were almost three times as likely to suffer dementia as vegetarians. I'd like to see Dr. Gupta explore this further.

I was also always curious about a potential link, though i suspected it might be the other way around, based on the old(??) cholinergic theory of depression whereby elevated levels of acetylcholine relative to the monoamines were believed to be involved in depression.

My mother died from Alzheimers a few years ago. There were several items that I remembered before diagnosis, and they were: preparing for a yard sale. The items she wanted to keep were put into zip lock bags, rolled and rubber bands used to hold them together. The rubber bands, so it bagan, the use of holding everything together. She used to save the rubber bands and put them into the lazy susan area of the kitchen. I must have found over 100 rubber bands in that one area. The rubber bands were from our local newspaper.
Another is starting to forget "how to cook!" She baked some macaroni and cheese and forgot to cook the macaroni first. It came out fine though. Playing with her jewelry. But being in deep thought, or maybe in a daze of knowing something is changing but not really knowing what it is.
My mother didn't do as much of asking us to repeat things, but would repeat things over to us. Maybe that is a scare tactic she felt that made her be sure to tell us important things. In hopes that we either wouldn't forget, etc.
She didn't wander, or get lost outside or in the house. When shopping toward the last of one of our outtings she would stop, and not turn around to see where I was, if she did not see me, she felt alone and a little scared.
Our last outting was sitting out from one of our diary queens and eating an ice cream cone. All the sudden she fogot how to eat this ice cream cone and was a little shaken about it. I almost did not get her into the car along with my very young grandson. That was when I knew that would be her last outting. Things happen like turning on a light switch.
Combativeness, she only would hit my sister, not myself or other sister. This only lasted a matter of months. My siblings all met and we decided that our parents would not be sent to any nursing homes.
We hired caregivers and had the most loving, caring people for our parents. We kept our promise!
I took her and my father, a retired attorney with the State Supreme Court here in our capitol city, every weekend on a drive and have breakfast. Talk about childhood and locate childhood homes etc.
My father has passed away with Parkinsons, and yes, it truly is the cousin to Alzheimers disease.
Now I am watching myself and noticing a few issues. But most of all, I quite smoking and I truly get sick more often and I heard that smoking kept you from getting Alzheimers, I do not know if that has been proven, but that is something to think about and test. There are alot of chemicals in the cigarettes that may fight or help you fight some diseases. Could there be a possibility in that?
I do know that my mom and I used to sew on a sewing machine alot.
Anything connected to those?
Exercise mentally and physically? I think there is something to these, people I know that have acquired Alzheimers were not very physcial and really were not a reader, etc.
When going through household items, I noticed aluminum pans, etc.
I have heard a little about aluminum being not good.
I do hope that we get through and find a cure, I am sorry that my great parents aren't here to see or feel it. I do hope it is soon.
I do not know much about depression, but I do think that stress can trigger the outbreak of these diseases. My parents were taking care of my grandmother when they first retired. And they would have done it no matter what. Family is family and comes first. They never were able to enjoy the comforts and or the joys of the "retiring years."
I am watching myself now, because I am showing more signs than my sisters and brothers. I will be 55 next month and hope and pray that I will see my grandchildren graduate and go on to college. That is my dream! Thank you for listening!
One and most important, my mother, even towards the end. If she could walk, I and my sibling would walk mother to bed. I would always sing and try to dance a little. She always tried to sing and move a little as though she were trying to dance. She always loved that, she loved music and loved to dance. We always tried to have soothing music for her to hear. Sometimes she would hum and when she couldn't hum anymore there was always a way we knew she could hear us. She died from Flu Type A, her little body couldn't fight anymore.
She never complained or never showed us she was frightened of this disease. She was a sweet and loving "Saint!"

My father struggled with depression in his 50-60's in our (children) opinion, before succumbing to Alzheimers which eventually contributed to his death in late 70's after about 10 years. He may have struggled with depression earlier as he was moody reportedly from an early age. I am 50 and have had recent bought of depression, which I think I turned around with stopping statin drugs, exercise, and better diet. There have been established extensive links of early onset dementia and ALz to statin drug use. A former astraunaut published an excellent book with references.

Dianne Lynn, I would want to know so that I could keep Dr. Kevorkian's or some similar practitioner's phone number ready in preparation. I guess you think I'm kidding. I'm not.

Dear Dr. Gupta,
I am from Barbados. My mother is 76 years old and suffers from Alzheimer's disease. Why is it that is has lost so much weight and still eating heartily. She is now 62 pounds.

She keeps developing a bed sore. Please help me because I look after her and am a working person. I have someone looking after her during the day and I play my part at night. I am 55 years old and a secretary.

>Wouldn’t it be great to know if you were likely to develop Alzheimer’s disease?
Why would it be great to know of one's chances of getting Alzheimers especially when there is no cure (like for most other diseases). Most people would live their lives in fear if they got an answer in affirmative and get the disease sooner because of the additional strain. Sometimes ignorance is bliss especially when the danger is potentially far away if at all. Given western medicines track record in "curing diseases" (and I meant it sarcastically) I think one is better off focussing on good lifestyle practices rather than what they can be afflicted with.

On our NursingHomeLaw Blog (http://blog.nursinghomelaw.org) we recently blogged about the effects that anti-psychotic medicine may have on Alzheimer’s patients. A new study in the UK found that patients with Alzheimer’s who repeatedly take antipsychotics showed a significant deterioration in their ability to speak fluently.

This study is important because many nursing home facilities around the country are simply overprescribing these types of drugs to patients without even thinking about more practical ways to handle them or calm them down.

The actual post can be found here:
http://blog.nursinghomelaw.org/2008/04/anti-psychotics-may-speed-alzheimers-decline/

Dr. Gupta, I was very intrigued to read your observations. My father, who turned 79 in January, was officially diagnosed with Alzheimer's Disease in October, 2006. His progression was quick, and we had to place him in long term care in May, 2007. It was too late for Aricept or other treatments to delay the onset. I would say he is about Stage 5 on the GDS, though he seems to be doing relatively well. What is curious is that we really cannot pinpoint when he began to show signs of the disease because some of them went to his usual demeanor and behaviour. It did not help that I was at odds, largely with my mother (having been married to my father for 56 years) in getting dad the diagnosis and ultimately the care that he needed. ("Denial" ain't just a river in Egypt.) What I have pondered in trying to educate myself and being the otherwise primary caregiver for my father is just how much of the events of his life may have contributed to his aquiring the disease: as a young boy, he was thrown from his bicycle after being hit by a car; as a teenager, he had a nervous breakdown following his parents' divorce; through his working life, he never showed signs of depression, though he had a career filled with so-called tension headaches; in his '60's, he suffered an acute (?) burst blood vessel in his left eye from the stress of my mother undergoing back surgery; and in his early '70's, he had a macular adema. While my father suffered both mental and physical traumas, depression in itself, in general runs on my mother's side of the family. I do have concern now about my mother's forgetfulness, and I am definitely the product of both my parents, having acquired my mother's depression (not so severe) and my father's migraines (more severe). While I am not sure if I would want to know if I was at risk for this disease, I would very much like to see more life-long studies as to just what might be contributing factors to the development of Alzheimer's. Like so many neurological illnesses, it is insidious, often a prolonged and painful grieving process for the patients and their loved ones. While Alzheimer's is not "an old people's disease", as our society ages, we need to support those in the field of geriatric research and care so that in the future, maybe we can more readily anticipate and treat the onset of the disease. There is no point in prolonging life if we cannot first ensure better life.

Dr. Gupta,

The abstract of the article you referenced seems to address an entirely different question about the depression-Alzheimer's relationship: whether depressive symptoms increase in the prodromal period before diagnosis of AD. And the conclusion of this study was "no."

Was the 3- to 4-fold higher risk of AD in persons with a depression history simply reference in the introduction or discussion section of this full article?

Please consider posting links to the source articles that document much higher risks of AD in people with a prior history of depression.

And I hope you did see the big Kaiser Permanente epidemiological study linking "central obesity" (belly fat) with Alzheimer's risk, which was published very recently in Neurology.

Knowing that a person could develop the disease “might” casue them to alter their lifestyle. I doubt many would.
For me i livea healthy lifestyle (diet and exercise). I would not wantot know that a potential debilitating disease or “death sentance” was in my future.

My mother passed away at 84. She was diagnosed with advanced dementia / possible Alzheimers. She started noticeably going downhill in her late 70s. The short term memory was shot, she'd get lost in the store, had no time orientation, forgot if she took her medicine or ate – but always knew she had to remember to do those things. I never knew her to suffer depression. She was always active, upbeat and positive. She traveled alot, read, worked crosswords while she could see. We reluctantly let her stay in the house with dad till he died. Their ongoing medical issues made us worry for their safety. When dad died, we shuffled mom through several nursing homes that each promised they could provide a level of care then it turned out they could not. During this transition, mom hated us. The nursing home did her in. While in their care, she fell, broke her hip and never recovered. It was very sad, but a blessing for all of us. I learned during this period that there are not enough support mechanisms for the aging or for alzheimer's patients.

Anurag, I agree with you on the statement you made: "Most people would live their lives in fear if they got an answer in affirmative and get the disease sooner because of the additional strain." I know that I have been pretty much miserable ever since hearing this news yesterday. Frankly, I am guessing that this kind of informational IED detonated on people who are struggling with depression and anxiety might be enough to push some over the edge to suicide. I am not one of them, but I can easily see it happening. One of the most important components in dealing with any emotional problem is the hope that things can get better. Take that away and you may as well cut people off at the knees.

This kind of info bomb dropped without the necessary context, perspective or discussion of potential mitigating factors is more than just exploitative and callous, it borders on cruelty. Count me out as a Gupta Groupie.

http://www.internalmedicinenews.com/article/S1097-8690(08)70198-7/fulltext

here is an interesting article about apoe4

Recs: 19 ApoE 4 Gene May kick Off Cognitive Decline/Internal medicine news

Apo E4 Gene May Kick Off Cognitive Decline: Homozygotes had the highest proportion of cognitive decline, with 40% showing domain decline.

MICHELE G. SULLIVAN (Mid-Atlantic Bureau)

Age 60 seems to be the defining year for many homozygous carriers of the apolipoprotein ɛ4 gene—the time when age-related changes in cognition focus more on memory and begin a steeper decline into mild cognitive impairment and, eventually, Alzheimer's disease, according to new unpublished observations from a longitudinal study of apo ɛ4 carriers and normal controls.

“We saw normal age-related patterns of memory loss that occurred before age 60, but during this period, we didn't see any significant cognitive differences between the apo ɛ4 homozygotes, heterozygotes, and noncarriers,” said Dr. Richard Caselli, a lead investigator for the Arizona Apoɛ4 Cohort Longitudinal Study of Cognitively Normal Individuals. “But our latest information shows that at around age 60, a separation begins and continues for as long as we have been able to follow our subjects. There is a particular pattern of decline in apo ɛ4 homozygotes that tends to precede any diagnosis of mild cognitive impairment [MCI] or anything that can be seen with routine clinical brain imaging,” he said in an interview.

This pattern suggests that pathologic changes could be occurring earlier in homozygous ɛ4 carriers, although the exact nature of these changes, and their triggers, remain speculative, said Dr. Caselli, chairman of the department of neurology at the Mayo Clinic, Scottsdale, Ariz., and a member of the Arizona Alzheimer's Disease Consortium.

The Arizona cohort was initiated in 1994, and now includes more than 600 people, enrolled at ages 20–90 years, who have at least one first-degree relative with Alzheimer's disease. The subjects are all genotyped for the apo ɛ4 allele and undergo extensive neuropsychological testing every 2 years.

Dr. Caselli's recent substudy focuses on 214 of these subjects aged 50–69 years. Almost half are apo ɛ4 carriers—43 homozygous and 59 heterozygous.

The study set out to characterize the effect of apo ɛ4 status on the development of presymptomatic cognitive changes. It's well known that the gene has a dose-response effect on the age at AD diagnosis: 80%–90% of homozygotes will develop the disease, at a mean age of 68 years. About 30% of heterozygotes will develop AD and will do so at a mean age of 73, while 9% of noncarriers will develop the disease and are usually diagnosed around age 80.

As in the larger cohort, subjects in the substudy took the neuropsychological test battery every 2 years. The battery consists of four tests in each of five domains: executive, memory, language, spatial, and behavioral. Significant decline was defined as a drop of two standard deviations beyond the decline of the entire cohort in one or more domain test scores. Subjects were judged to have cognitive domain decline if their scores were lower on at least two tests in any single domain.

“We found that there was really no difference between the genetic subgroups in patterns of decline in the younger group of patients, aged 50–59 years,” Dr. Caselli said. “Some had no decline, some showed improvement, and some had domain decline, but there were no statistically significant differences.”

Significant differences did emerge in the group of 60- to 69-year-olds, however. Homozygotes had the highest proportion of cognitive decline, with 40% showing domain decline, compared with 8% of heterozygotes and noncarriers. None of the older noncarriers or heterozygotes experienced a decline in two or more domains, while this occurred in 20% of the homozygous subjects.

Dr. Caselli has additional data on 97 subjects who have been tested again in the years following their initial decline. “We saw that it was those who initially declined on memory who tended to continue to decline significantly in other areas, and if that subsequent decline was in the memory domain, it was even more pronounced.”

Seven subjects developed MCI or AD during the study; five of these were apo ɛ4 homozygotes, one was an apo ɛ4 heterozygote, and one was a noncarrier. “Typically, it took about 2 years following the epoch of domain decline for the diagnosis to occur.”

By looking at the larger cohort and including subjects aged 30–90 years, Dr. Caselli also found a striking age-related separation of memory domain performance between apo ɛ4 carriers and noncarriers. From age 30 to 60, memory performance on the Auditory Verbal Learning Test, which requires subjects to recall 15 words from a list, declined slowly and consistently, from a mean of 11 words at age 30 to about 9.5 words at age 60. Immediately thereafter, however, the groups separated. Noncarriers continued a slow, almost linear decline, and by age 90, their predicted mean word recall was about 8.5 of 15. But carriers entered a phase of sharper decline; by the time they reached 90 years, their predicted mean word recall was about 5.5.

The slope of decline exhibited by the noncarriers represents normal, age-related memory loss, Dr. Caselli said. The sharper post-60-year decline in apo ɛ4 carriers probably reflects a direct or indirect effect of the ɛ4 gene.

But although these cognitive changes appeared mainly after age 60, imaging studies on some of the younger carriers suggest that some brain areas may be vulnerable much earlier in life. PET scanning of presymptomatic 50- to 59-year-old homozygotes showed areas of decreased glucose metabolism in brain regions associated with Alzheimer's disease pathology: the posterior cingulate gyrus, parietal and temporal lobes, and prefrontal cortex. PET scans of 20- to 39-year-olds with one copy of the allele showed similar, although smaller, areas of decreased metabolism.

“So what does that mean?” Dr. Caselli asked. “If you look at all the work out there—the Nun Study, brain imaging, and pathology studies of apo ɛ4 carriers—you get the idea that little pieces of AD pathology happen throughout young adult life, but we don't see young people developing progressive dementia unless there's an autosomal dominant mutation. The fact is, we don't know whether these early changes reflect a sort of nonprogressive pathology or some basic biologic vulnerability that marks the territory of later decline.”

There are plenty of theories about the possible connection between apo ɛ4 status and Alzheimer's pathology, Dr. Caselli said. Most focus on the pathologic function of the apo ɛ4 isoform. Research from the 1990s suggests that it enhances amyloid deposition, reduces neurite outgrowth and protection against oxidative stress, and cuts the efficiency of neuronal and synaptic repair.

Most recently, researchers at the University of California, San Francisco, have suggested that the apo ɛ4 isoform can generate a cytotoxic carboxyl fragment. This truncated form of the protein is thought to induce neuronal inclusions that are similar to neurofibrillatory tangles, containing phosphorylated tau and high-molecular-weight neurofilaments (Proc. Natl. Acad. Sci. USA 2001;98:8838–43).

“The science on this is pretty well established, but whether it's key to AD pathogenesis is still undergoing further study,” Dr. Caselli said.

Another recently proposed connection is the relationship between apo ɛ4 status and the demyelination in the frontal lobe and corpus callosum, Dr. Caselli noted. These brain regions, which continue to lay down myelin until middle age, also appear most susceptible to myelin breakdown, wrote Dr. George Bartzokis, director of the UCLA Memory Disorders and Alzheimer's Disease Clinic in Los Angeles.

Dr. Bartzokis's study of 104 healthy subjects aged 75 years and younger found that those with the apo ɛ4 genotype had the highest level of demyelination in frontal lobe white matter and the genu of the corpus callosum. The apo ɛ2 genotype appeared protective of demyelination, while those who were apo ɛ3 positive had an intermediate level of demyelination.

The connection may be the dearth of apo ɛ molecules in the ɛ4 genotypes. Apo ɛ helps maintain neuronal health by degrading damaged myelin and recycling the lipids for rapid repair. Those who are apo ɛ2 positive have the highest number of apo ɛ molecules available for this constant repair process; those who are apo ɛ4 positive have the lowest number, while apo ɛ3-positive subjects have an intermediate number (Arch. Gen. Psychiatry 2006;63:63–72; Proc. Natl. Acad. Sci. USA 2006;103:5641–3).

The lack of sufficient myelin repair “causes a progressive disconnection of widely distributed neural networks that results in cognitive decline and contributes to the age risk factor for AD,” Dr. Bartzokis wrote. This pattern of demyelination may be what scans are picking up in the Arizona cohort, Dr. Caselli said, although there could be other explanations as well.

The theory of apo ɛ4's pathologic effect on neurons has faced an uphill battle for years, Dr. Caselli noted. “It was initially met with a lot of skepticism because it had nothing obvious to do with amyloid or tau, so it didn't fit the prevailing paradigm of AD pathogenesis. It's been worked on extensively to make it fit, and as of right now, we're still not completely clear about how it does.”

My father's death certificate calls out two causes of his death at 76 artherial (spelling is probably wrong) and senile demenia of the Alzheimers type. I watched him deteriorate over a 20 year period, which included becoming agoraphobic. During the 20 years he was in a state of depression, and had probably suffered boughts during his life without knowing it. He died in 1985.

Thank you for sharing this information. As I tend to favor his side of the family and we are sure his grandmother probably also suffered from Alhzeimers I have a genuine concern about my own aging process. But for me this is good news as I do not show symptoms of and have not been diagnosed with depression!

My parents split up my first year of college (youngest child). After being a wife and mother and homemaker for all her adult life, my mother found herself in a very depressive situation; basically a severe case of empty nest syndrome made worse by a divorce after 30+ years of marriage. I know she suffered from depression for some time and (not) coincidentally, began suffering cognitively a short time afterwards. She's now only 62 and has moderate Alzheimers and requires the type of care only provided by assisted living.

I'm not saying there was a definite cause and effect relationship here but my personal experience with a family member suffering from depression followed by early onset Alzheimers seams to fit this trend.

My mother is 76 and has alzheimers. She lived a very difficult life, being orphaned at age 5 and later marrying my father a manic depressive. She learned not focus on any memory that caused her pain. She would "blank it out." I think she went too far.

I worry that my mother, who has suffered with depression and is rather forgetful, will develop dementia. More so after reading this. If there were a test that could tell us whether she has or will develop AD, I would want to get it for her.

I would want to know about it for myself, but I would not take such a test, because even having that test show up on an insurance bill would make sure I never got insurance again. I'd do it after I am eligible for Medicare and can't be turned down.

Alzheimer's or Dementia??? That question in itself is as confusing as the disease! My mother has had what was diagnosed as Alzheimers for seven years now, taking Namenda and Razadyne also for seven years. I moved her from Arkansas to Montana to live with me so I could take care of her. I started to notice I was forgetting things and losing things more than "normal". I read somewhere an MRI or PET scan might help determine the beginning of Alzheimer's so I had an MRI done with the thought that if I knew I was "beginning" to develop it, I would WANT to me on the medication since it had helped my mother for so many years. She is still in the moderate stage after seven years. I was told that the medication only works for Alzheimer's for two years, so my mother must have dementia instead. The doctor said to take her off her medications for a few days to see if there was any decline, and there was, so I immediately put her back on her medicines. This made no sense to me as the medicine seems to work, so I don't know if it's Alzheimer's or Dementia. Everyone seems to have a different theory...what I know is that it's a horrible disease. What more can be done to care for the person with the disease and the caregiver that also suffers from the stress and depression. It's like being handed a life sentence, knowing that it all comes to full circle – Alzheimer's + caregiving = stress = depression = stress related diseases that can kill the caregiver. Will this circle ever end?

Mark S and Anurag, I agree and disagree with you in part. I'm quite uplifted by the prospect of knowing, and have been waiting for it with baited breath for at least five years. Here's why. I watched Mama wither to the weight of a small skeleton and finally die in 1998 at age 68. Daddy kept her alive at home for 18 months with hospice after he went behind my back and approved a G-tube when she ceased to swallow (one of Alz's less favorable , a common result of Alz). Daddy fought and won each and every battle with pneunomia because someone helped him learn about morphine. I can't tell you exactly the point, but months had passed and I knew she had moments of lucidity, which turned the horror to trauma for me. After Mama's body quit receiving any nutrition from the tube, the doctor told him to quit feeding her. She starved for 13 days but wouldn't die. Daddy confessed that he had still been giving her water and meds. The doctor stepped in (finally). She lived eight more days. Her tongue was unrecognizable, and there was no tenable evidence of moisture anywhere in her body. She breathed her last breath in my face. She regretted her children and was severely depressed for all of the 35 or so years of which I was cognizant. She never, ever did anything about it with one most important and valuable exception - she made her wishes known in advance. I was present when she signed a durable power of attorney for health, but Daddy did not respect and enforce it; and I was unable to have him legally removed as power of attorney. I am determined this will not happen to me. Based on the long history of depression and early mortality of the women on my mother's side, and my current battles with nightmares coupled with depression, I WANT TO KNOW (1) as soon as I can get tested to learn if I'm sympathetic to Alz; (2) so I can make my own arrangements, up to and including tattooing DO NOT REVIVE on my chest and forehead if necessary; and (3) so I will be better armed with lawyers and doctors to assure that my rights and wishes are respected and enforced. I can't count the number of nursing homes that I have been in and, I can assure you, NOTHING beats the comforts of your own home or the location that you choose, doing the things you choose, for as long as YOU CHOOSE. I think it is important that people know the horrors of Alz if it is left to complete its cruel cycle. Everyone I talk to think Alz patients are just plump little old men and ladies who can't remember anything or cease their positive function in society. That may be the experience for most folks, but it was not mine. I'm sharing this in case someone else is facing or going through the same thing. Grace, peace and know your rights!

Keep up the good work, Dr. Gupta. You're doing the right thing!

'Wouldn't it be great to know if you were likely to develop Alzheimer's disease?' No, it wouldn't be great! I mean, are you serious?? What would be great about it, exactly? it's not as though you could do anything about it. Just give you the gift of fear and depression a few years or decades before the disease actually hits. Thanks a lot, doctor.

This is an interesting article to me, especially since my father died of Alzheimer's in October 2006. His brother also died of the disease and depression and anxiety runs in his family. I hope and pray that Alzheimer's stays a priority for researchers and our society. It is a devastating disease and was extremely difficult for my family to watch our loved one succumb to it. Thanks Dr. Gupta for yor research.

My maternal grandmother fell into deep depression after one of her sons died in WWII. She developed Alzheimer's shortly afterward and died at 71.
Her daughter, my mother, had bouts of depression after menopause, which deepened after my father got seriously ill. She began to show signs of forgetfulness and her logic thinking waned also. When she was 82, my father died and after that it was a steep free fall into mental decline. She now is 89, physically as healthy as a horse, but does not remember any of her children and thinks she is 19 years old.
As a side note, she also had other precursors of AD:constant infections (gums) and extremely high cholesterol (over 300) that went undetected for many years. She was, however, very slim and trim and physically very active. In fact, when she was 86, she could still outrun me and I am in great shape!
We need to find a cure for AD ASAP! It is truly the most horrible illness.

Not all night terrors may be caused by this, but on a night-terror news special, I noticed many victims were over weight. Could night terrors be caused by cholesterol medication? The medications list nightmares as a side effect. Both my mother and mother in law had to stop taking cholesterol medication due to horrible nightmares caused by it.

My father was diagnosed with Alzheimer's at age 74 and passed away at age 81. He was a retired minister and had one of the most even temperaments I have ever seen. However, this is a high-stress job and keeping his emotions and negative feelings hidden went with the territory. I'm sure that he was depressed many times, but had to keep this private. My siblings and I agree that he started showing signs of Alzheimer's a few years after my mother suffered a heart attack, which happened when he was 60. He stayed round-the-clock at the hospital and was severely sleep-deprived during the course of her hospitalization and after her return home following open-heart surgery. We all felt that the sleep deprivation and constant worry precipitated his Alzheimer's disease. He hid it from us for a long time and we finally convinced him to see a neurologist when he was 74, at which point the diagnosis was made. His mother also had Alzheimer's; she suffered from depression at an early age following the loss of a child whose appendix ruptured. She never showed much emotion after the loss of that child, had a rather flat affect. She was in her 30s at the time her depression started.

Man, this was a shock! Both my husband and I have had depression for years. My father died from complications of Alzheimer's in his eighties. I don't know if he was depressed. My mother was chronically depressed for most of her life but did not seek treatment. She died of pancreatic cancer at the age of 70. Would she have developed Alzheimer's later? Who knows? Suffice it to say, neither of us wants to develop Alzheimer's and would most likely have an exit strategy should that happen. We're hoping that exercising and healthy lifestyles will stave off the disease.

Barry – The benefit of knowing you might be in early stages of Alzheimers is that you could start medication that would slow the progression. I would rather know and be on medication that would keep my mind better longer, than not start medication until I was in the upper mild to moderate stages. If you knew, you'd have more time in your life to enjoy. This is just my feeling on it. The question still arises though, does the medicine really only work for two years as the doctor told me, or does it work indefinitely as it has with my mother for seven years. I would rather know early on and do what I could to keep my brain from deteriorating that to live my life wondering if I were going to get, do I have it, etc. and not doing anything about it. The unknown can be pretty scary with Alzheimer's.

A few comments if I may....

First, Grandma B.–I found caregiving for my mother to be hell on earth.
You deserve to have your own life and I would strongly suggest that you find outside care or iving arrangements for your husband. My mom actually improved when I moved her to an Alz. unit at a nursing home, and I was able to get my mind and life back as well. She is cared for by loving, dependable, and enjoyable staff...which is a far cry from the person who was taking care of her here.

Second, I truly believe that my mom's Alz. was caused by long-term untreated depression, 20 or more years, and by the equally long-term use of hormone replacement therapy. Both affect the seratonin levels in the brain and the sucrose levels as well.

Her initial symptoms mimic the others discussed herein; especially the lack of awareness of time & seasons and paying bills repeatedly.
She's now going on 64; she lived here for 5 years as the disease progressed.

Helpful information is found at Alz.org; including their "Maintain Your Brain" program.

While I have been successfully treated for depression for the past year, it is still very scary to think that this is the beginning of the end.
And, yes, you need to be your own health advocate and seek out other knowledge and opinions. As in every profession, some can't/don't/won't keep up with the latest information and it's up to us to take care of ourselves.

My father was in a nursing home almost 5 years before he passed 10/10/ 06 with Alzeheimers. His married life was very stressful but he always would make a joke of everything and laugh it off. He also like taking medicine. Thanks for the info as I am very interested in finding any info on the subject of Alzeheimers. Judy W.

There is an NPR podcast dated 1/16/08 (Insider Forums / News Hour – I downloaded from Itunes) which is worth listening to if you are interested in early signs of Alzheimer's. Interviewer talks w/3 men diagnosed before age 55 about signs/symptoms. Very interesting and informative.

Further to last comment about interview w/3 men who had early onset Alz ... here are a few notes: 1) one had severe insomnia
2) complex yet ordinary day-to-day work tasks began to take a very long time to complete for another 3) it took 18 months for one man to receive a proper diagnosis of Alzheimer's – patient was diagnosed and treated for depression, but knew there was something else going on 4) they all concurred that a combination of PET scan + battery of functional tests for Alzheimer's were the best way to absolutely diagnose it 5) at least one patient was being successfully treated by a combination of drugs. All patients interviewed had been diagnosed in late 40's – early 50's. All were professionals (two had been IT executives). All were certainly quite articulate and well-spoken 6) one patient had had multiple head traumas, several of which he'd been hospitalized for ... said he'd played football when young. This is just a summary of points I remember from this podcast.

When the neurones circuits break, it is often due to accumulation of nervosity,anxiety,stress.

It would MOST DEFINITELY make sense to me that depression, in all likelihood would be a contributing factor of Alzheimer's Disease.

My Dear Mother, who most recently passed away at the age of 80, in the South FL region was a Survivor of the Holocaust. My Dear Mother, may she Forever Rest in Eternal, Heavenly Peace, practically lost her Entire Family as a result of the most evil third reich and as a result, she was naturally depressed; however, she was Absolutely SUPERB in covering up her innermost feelings and emotions. Anyone that knew my Dear Mother would NEVER think she suffered from depression whatsoever.

Approximately 10-to-12 years ago, my Dearly Beloved Mother started showing early warning signs of Alzheimer's Disease. By the time she was 68-Years Old, she had already started forgetting simple things such as her SS #, home telephone #, street address, birth dates, etc. I had literally begged my Dear Mother to see a Doctor to at least have her tested for possible early warning signs of Alzheimer's; however, she took my request and suggestion very offensively and positively refused to undergo any such evaluation at her Doctor's office.

Now, here we are 12-Years later, and my sweet Mother, unfortunately lost her battle with Alzheimer's Disease back in September 2007. It was devastatingly heartbreaking for me and my Dear Father, who is still living, and ALSO a Holocaust Survivor. But, obviously, at this point there's not a whole lot we can do.

Bottom line – My utmost recommendation would be, if you detect early warning signs in your loved ones, who might forget simple things such as their own home telephone #'s, SS #, street address, birth dates, etc., then for Heaven's Sake, by ALL MEANS, have your loved one evaluated by a professional Doctor. Alzheimer's Disease is NO JOKE AT ALL !! And although my Dearly Beloved Mother lost her battle with this devastating illness, there are medications out there that might help in prolonging your loved one's battle such as Aricept. My Mother was prescribed Aricept, but unfortunately, she was not fully diagnosed until she was already in the latter stages of Alzheimer's Disease.

When my Mother was in the final stage of Alzheimer's Disease, she was placed in a Hospice Care Unit at the local Hospital down in the South FL region she lived in. I cannot even begin to tell you just how heartbreaking it was to witness my Mother's brain literally shutting down all of her organs. I MISS HER TERRIBLY !!

Mark L. – the L-ord bless and comfort you. You are a mensch!

I need to know what to expect when my mother who I watch is going to die with pain. What can I expect when it progresses. She is 85 years old with alzheimer, and I don't know if I can take the fact that my mom who was a beautiful caring person will die soon. She is acting more and more like she is in the downward cycle.

Please answer my questions
I need to be prepared

Thanks
Dorothy