Depression superimposed on dementia–two hits to the brain!!!

Depression superimposed on dementia–two hits to the brain!!!

Nitin K Sethi, MD

Assistant Professor of Neurology

New York-Presbyterian Hospital

Weill Cornell Medical Center

New York, NY

In recent years the link between depression and dementia has been closely looked at.  Many questions await a definitive answer-

do attacks of major depression predispose to dementia later in life?  (or put in more simpler terms, does depression hurt the brain and kills  neurons leading to cerebral atrophy and dementia?)

is depression more common in patients with primary dementia such as Alzheimer’s dementia?

is depression frequently missed or misdiagnosed in  patients with primary dementia ?

do patients with dementia have depression which is more refractory to medical treatment?

does depression accelerate the rate of cognitive decline in patients with dementia?

I recently saw a patient who was referred to me to evaluate for dementia. She was 74-years old and her past medical history was significant for hypertension for which she was on anti-hypertensive medications. When the patient saw her primary medical doctor she had volunteered the information that she was having some problems with her memory. She at times forgot the names of her loved ones, one time she had got lost while heading from home to the hospital. Her home aide further added that she had noticed that the patient frequently misplaced objects and then could not recall what she had done with them. At times she forgot to add an essential ingredient to a dish she was preparing. Recent neuropsychological examination was suggestive of a primary dementia.

As I spoke to the patient, I found her to be quite high functioning. She made eye-contact, gave a succulent history and most importantly had insight into what was plaguing her namely her problems with memory. As the interview went on I learnt that she had been depressed for a while. Though she was on anti-depressants, the recent loss of close family members had made her more depressed. She suffered from a loss of appetite and few things in life gave her pleasure.

So where do we go from here? What is the optimum treatment for someone who might have an underlying primary dementia such as Alzhemier’s disease but also has superimposed incompletely treated depression. Most doctors would agree that her depression needs to be treated more agggressively but the questions which arose in my mind were the following:

–should I treat her for dementia now or reassess her after treating her depression more aggressively?

–is the ongoing chronic depression actually predisposing her to memory problems and maybe even dementia?

–what came first—depression or dementia?

–who is the bigger culprit here–depression or dementia?

All questions for whom we still do not have good answers.  The brain can take a hit here and there but depression-dementia is a deadly combo–likely a death blow to the delicate brain. Maybe one day we shall be able to win the battle against these two scourges.

Behavioral problems in dementia, how common are they and is there any help for it?

Behavioral problems in dementia, how common are they and is there any help for it?

Nitin K Sethi, MD


I recently saw a 75-year-old patient in my office which has prompted me to write this post. His wife brought him in  for memory problems. As I took the history, I realised that it was not memory problems per se that was bothering her, it was his change in behavior. Recently he had become aggressive, at times verbally and physically abusive to her. True he had some memory difficulties which were apparent in the history. He had lost his way once and got confused when he could not recall the names of his grandchildren at a family get together. But as I took his history and asked him questions, I found him to have a good fund of general knowledge. He was aware of recent events like the election of President Obama and the war between Israel and Hamas. He was physically active and liked to cycle around the neighbourhood. But it was his change in behavior which was causing a strain in his relationship with his wife and she was having a difficult time taking care of him and administering all his medications.

The patient above obviously has dementia settling in. One can argue about the type of dementia (is it Alzheimer’s or some other type of dementia such as fronto-temporal dementia? You can read more about the same on my website But what I wanted to stress in this post was the prevalence of behavioral problems in dementia. Behavioral problems are common in all forms of dementia and are a frequent cause of caregiver stress and burnout.  Patients with dementia may present witha multitude of behavioral issues. They may either become too aggressive and hard to control (verbally and physically abusive they may lash out at loved ones when they attempt to nurse them) or they may become aphathic with loss of motivation and drive. Caregivers may complain that they are listless, just sit in one place thoughout the day and do not attempt any new task on their own.

I want to stress that caregivers need to understand that these behavioral problems are a part and parcel of the dementia complex. Lot of people just associate dementia with memory problems, little realising that the disorder is more pervasive. Thankfully now there are many drugs which can control some of these behavioral issues, thus making life easier for caregivers. These range from antidepressants to antipsychotic drugs apart from cognitive and behavioral therapy.

My advise to my readers is this.  If any of you has a loved one with dementia, learn to recognize behavioral problems early on. Bring them to the attention of the doctor since many of them can be effectively treated.


Statins reduce risk of incident Alzheimer’s disease?

I recently read an editorial in the Journal of Neurology Neurosurgery and Psychiatryby Dr. Larry Sparks about statins and cognitive function. Multiple studies have hinted at reduced risk of incident Alzheimer’s disease with elective statin use. I thought this would be worthwhile to share with the readers of my blog and website (

As I stated above, multiple studies have linked a high fat/ high cholesteroldiet with increased risk of Alzhemier’s dementia. Hence many studies have been carried out to determine if lowering cholesterol levels with the use of statin group of medications (these are popular cholesterol lowering medications with names like atorvastatin (Lipitor), simvastatin (Zocor) among others) reduces the risk of Alzhemier’s dementia. While some studies have indicated a benefit others have provided contradictory results indicating little to no benefit on cognitive functioning.

As Dr. Larry Sparks states in his editorial there is likely a small subset of patients who will benefit from statin therapy. The trick lies in identifying these patients early on in their disease course from others in whom there is little or no benefit from statin therapy. Also it seems that some statins may be more beneficial than others when it comes to reducing the risk of Alzheimer’s dementia. This difference is likely due to their individual differences in blood brain barrier permeability (meaning to what extent they are able to penetrate the brain).

Till we are better able to identify this subgroup of individuals, there are certain things which we can implement in our own lives to tilt the scales in our favor. A low fat, low cholesterol diet should be encouraged. The cardiovascular (lowering the risk of myocardial infarction)and possible neurological benefits (with respect to possibly reducing the risk of incident Alzheimer’s dementia and stroke) makes this a very attractive proposition. Moreover this is a relatively cheap intervention. It though needs a comprehensive strategy to educate the public about the benefits of a low fat/ low cholesterol diet ( about the benefits of eating right {more vegetables, less of red meat and saturated fats} and incorporating a regular exercise schedule. People who already have cardiovascular risk factors like hypertension, diabetes mellitus and high cholesterol (dyslipidemia) should talk to their doctors about possible statin therapy.

I want to add that statins just like any other medication do have their own risk of side-effects. They thus should only be taken under the supervision of a physician.

The adage ” Eat right, live long and happy” still holds good!!! To that I would add ” EAT RIGHT, SAVE A BRAIN!!!”

Nitin Sethi, MD

Deficiency of vitamin B12 causes cerebral atrophy

                               Deficiency of vitamin B12 causes cerebral atrophy

                                                    Nitin .K. Sethi, MD

                                            Assistant Professor of Neurology

                                            New York-Presbyterian Hospital

                                              Weill Cornell Medical Center

                                                New York, NY 10065

I am big on vitamins both when it comes to taking it myself and recommending it to my patients. So my interest was naturally piqued when I read an article in the journal Neurology titled ” Vitamin B12  status and rate of brain volume loss in community-dwelling elderly” by Vogiatzoglou et al. The authors investigated the relationship between markers of Vitamin B12 status and brain volume loss in an elderly population. They concluded that low levels of vitamin B12 may contribute to brain volume loss (cerebral atrophy) and may be one of the causes of subsequent cognitive impairment in this population. So how do we interpret this data?

Can vitamin B12 intake prevent the onset of dementia.?

 If so how much of this vitamin should one take?

And at what age should one start taking this?

Questions for which we still do not have good answers. As I see it, vitamin B12 is pretty innocuous (side-effects are few if any) and thus can be safely taken by the majority of people. Moreover it is cheap (as unlike some other vitamins and anti-oxidants in the market eg coenzyme Q10). Dementia is a devastating neurodegenerative condition for which at present there is no cure. If vitamin B12 intake prevents cerebral atrophy then it may be worthwhile recommending it to my patients.

The elderly are a vulnerable population group. Many times their diet is marginal and thus they are prone to having nutritional (vitamin) deficiencies.  Other vulnerable groups include alcoholics (people who drink heavily, usually have marginal diets and thus are prone to vitamin deficiencies), people who have conditions which prevent the body from absorbing vitamin B12 example pernicious anemia, those who have had bowel surgery, Crohn’s diseases, ulcerative colitis etc.

Vitamin B12 is present in meat including fish, poultry, eggs, milk, and milk products. It is important for neuronal function and also helps to maintain healthy red blood cells. So deficiency is more commonly seen in vegetarians especially those who do not have even milk or milk products. It is this group whom I feel shall surely benefit from vitamin B12 dietary supplementation.

At what age should one start taking Vitamin B12 is difficult to answer. Vitamin B12 is stored in the liver and so a person who eats a healthy diet should have ample reserves of this vitamin and does not need supplementation. I usually check the vitamin B12 status of my patients especially those who are elderly or suffering from a chronic medical condition. This can be done by a simple blood test. If they are deficient, I prescribe vitamin B12 (vitamin B12 comes in tablet form. In patients who have very low stores, we sometimes give them a shot of vitamin B12 intramuscularly).

As for the rest of us (“healthy” and not too old) what should we do? One way would be to take a tablet of multivitamin a day. Most good multivitamin combinations do have B12 in them. That is what I do!!!

” the mind is a wonderful thing and a healthy mind is truly beautiful”

Falls in neurodegenerative conditions: what can be done?

               Nitin K Sethi, MD

Assistant Professor of Neurology

New York-Presbyterian Hospital

Weill Cornell Medical Center

New York, NY 10065


Falls are common in neurodegenerative conditions so that is what I shall discuss in this post. Patients with diseases like Alzheimer’s dementia, fronto-temporal dementia (Pick’s disease), multi-infarct dementia (vascular dementia), Parkinson’s disease, multiple sclerosis, Progressive Supranuclear Palsy and some post stroke patients are all prone to falls either early or sometime in their disease course.


Falls are an important cause of morbidity and mortality in this vulnerable population. Imagine a-85-year old man with Alzheimer’s dementia. Even though he has cognitive deficits (decreased memory and problems with other cognitive skills like calculation, abstract thinking and language) he is still relatively mobile. Every day he takes a 30 min walk in his immediate neighbourhood. One day while walking, he trips over and falls when his foot gets caught in a crack in the side-walk. He is unable to get up by himself . Help only reaches him after an hour when his family comes looking for him. He is rushed to the nearest hospital where an X-ray reveals fracture of the hip and the pelvis. Surgical management is indicated for fracture stabilization.  He is admitted to the hospital and the hospital course gets complicated by development of pressure sores (bed sores), deep venous thrombosis (blood clots in the veins of the legs) and pulmonary embolism (blood clot in the lung vasculature).  All these are directly related to his forced immobilization due to hip and pelvic fractures. He gets progressively more disoriented during his prolonged hospital stay though survives and makes a slow recovery and is discharged to a sub-acute facility.


Falls may lead to various injuries:

1) Fractures of the hips, long bones: tibia, fibula, femur, neck of femur, radius, ulna

2) Neurotrauma: head injuries: subdural and epidural hematomas, sub arachnoid hemorrhage, intracranial hemorrhage (bleeding into the brain)

3) Craniofacial injuries: injuries to the face, eyes, the orbit

4) Fractures of the ribs

5) Back injuries


The incidence of hip fracture increases as the population ages. One in five persons dies in the first year after sustaining a hip fracture, and of those who survive past one year many have significant functional limitation. Of those who survive one year after hip fracture, only 40 percent can perform all routine activities of daily living and only 54 percent can walk without an aid.


Why are falls common in the elderly and more so in the elderly population with a neurodegenerative condition? The causes are many:

1) Poor eye-sight (as we age cataracts and other retinal degenerative conditions become common contributing to poor eye-sight). They have poor depth perception and visual contrast sensitivity.

2) decreased acuity of hearing

3) concomitant neuropathy (many of the elderly population may have a condition like diabetes giving rise to a concomitant peripheral neuropathy. Persons with a sensory motor polyneuropathy are not able to sense the ground and thus their righting reflex is off). RIGHTING REFLEX: various reflexes that tend to bring the body into normal position in space and resist forces acting to displace it out of normal position.

4) Neurological conditions like Parkinson’s disease and Alzheimer’s dementia impair these postural reflexes/ righting reflexes making patients even more prone to falls and resultant injuries.

5) The elderly are on multiple medications like  benzodiazepines, anticonvulsants, sedatives and  antihypertensives which may contribute to the falls. 

6) Risk of osteoporosis and osteopenia increases as we age: when the elderly fall they are more likely to hurt themselves or fracture their bones.

7) Other concomitant medical conditions like diabetes, kidney problems, thyroid problems, blood pressure problems and cardiac problems may contribute to the falls.


The big question is how to prevent falls in the elderly. A number of interventions may help.

1) Treat the neurodegenerative/ underlying condition contributing to the falls. Gait and postural reflexes of patients with Parkinson’s disease improve when they are treated with medications like Levodopa-carbidopa and dopamine agonist. The response though varies, their tremor may improve though their gait may still remain off.

Good control of blood sugar in a diabetic patient helps and may halt the progression of the neuropathy.

Alzheimer’s disease patients also gain some benefit in their gait and mobility when they are treated with medications like Aricept.

2) Correct visual/ eye problems: timely cataract surgery, corrective lenses and glasses all help in improving stability and confidence of the elderly patient.

3) Hearing aids may be of help in those who have hearing loss.

4) Restriction of outdoor activities may be advisable in a patient who is at high risk of falls. If that is not acceptable, these activities should be carried out under direct supervision. Keep a walking partner etc.

5) Correct mechanical/ musculoskeletal gait problems such as ingrown toe nail, back and hip pain, foot drop etc.

6) Regular exercise is helpful. By keeping muscles supple and maintaining their tone it ensures that righting reflexes are not lost.

7) Physical therapy may be immensely helpful in some patients (laying emphasis on gait retraining).

8) Use of assist devices like canes (single point, four point), walker is helpful.

9) Fall proof the home and immediate patient surroundings: remove anything which may cause injury if the patient falls-this includes sharp objects, tables with sharp edges, loose carpets.

have fall prevention devices at the top of stairs.

have a bed whose sides can be put at night (just like in the hospital).

have an alarm or some other call device set-up at home so that help can be summoned.



The neurology of aging

Is aging normal or abnormal/pathological? No one quite knows the answer to that question. What we do know is that as we age, neurological disorders become increasingly common. These may range from well defined neurodegenerative diseases like Alzheimers dementia, Parkinson disease and amyotophic lateral sclerosis to other less well defined conditions like gait disorders, “balance problems”, “forgetfulness and senior moments” and increased propensity to falls. Strokes become more common in the aged brain vessels.

As life expectancy increases and more and more people live past the eight decade, neurological conditions become common and account for substantial morbidity and mortality in the oldest old (above 85). Earlier when the life expectancy was in the 60s, we did not see so much Alzheimers dementia, Parkinson’s disease or brain tumors. People died of other “natural” and “unnatural”  causes before the brain showed clinical manifestations of neurodegeneration.

Is it the norm that as we age, a substantial majority of us are destined to develop dementia?  Clinical studies have clearly shown that Alzhemier disease pathology increases with age and the incidence of the disease becomes increasingly common as one goes past 85 (the oldest old). Other studies suggest that though not all the oldest old show clinical dementia, a substantial majority have cognitive difficulties if carefully tested for at the bedside.

Why do neurological conditions become more “common” as we age and can we do anything to alter this? Many theories have been propounded. Increased amyloid deposition in the brain has causal association with Alzheimers dementia, in the same vein deposition of iron in the basal ganglia has been postulated to cause various basal ganglia pathology. There is increased oxidative stress in the “aged” brain which leads to free radical formation and damage to the cellular DNA. Genes get switched off or on triggering the disease process. A lot still needs to be learned about the neurology of aging.

While the mechanisms are still been elucidated, is there anything which we can do to change our “risks”. In the absence of good studies most of the data is open to interpretation. Aspirin prophylaxis, modification of microvascular and macrovascular risk factors like hypertension, diabetes mellitis and dyslipidemia (high “bad” cholesterol) all seem to be reasonable interventions. Obesity and sedentary life styles are bad for the brain too. Regular physical as well as brain exercises (neurobics) keeps the brain healthy and increases neuronal reserve. The role of anti-oxidants like coenzyme Q10 and alpha lipoic acid is still been defined. As they are relatively innocuous and free from side-effects, I would recommend them on a case by case basis. Episodes of major depression “hurt” the brain and aggressive treatment with anti-depressants should be initiated early rather than late.

The neurology of aging remains an uncharted territory but there is hope yet.

Nitin Sethi, MD


Another interesting article in the Wall Street Journal by Melinda Beck where she talks about neurobics or rather mental exercises which may have a role in preventing or rather delaying the onset of neurodegenerative diseases like Alzheimer’s dementia.

As she rightly points out in her article, the etiology of Alzheimer’s dementia is thought to involve genetic and environmental factors and it is unlikely that mental exercises (neurobics) shall prevent the onset of Alzheimer’s dementia. But research and studies have shown that people who have a good neuronal reserve (higher intellect) seem to fair better when they get stricken by Alzheimer’s dementia as compared to people who are less educated and I guess with lower neuronal reserve.

So I would advise everyone to indulge in neurobics everyday. It is easy to do, has no side-effects and possible benefits.

Some neurobics I recommend:

1) If you are right handed, try brushing with your left hand (and vice versa if you are left handed).

2) If you are right handed, try eating with your left hand (and vice versa if you are left handed).

3) try writing with your non-dominant hand (now this is hard and painfully slow at times)

4) do crossword puzzles, number games

5) learn to play chess

6) learn to play a musical instrument (drums are great since they require a lot of hand coordination)

7) avoid using palm pilots and hand held devices. Commit more things to your memory. You do not need a palm pilot to remind you what you going to do during the day.

8)  Read books and newspapers instead of watching TV all the time. Remember when you are watching TV, you are doing nothing. You are just a passive spectator. When you read, you use your brain.

9) avoid using calculators. Try to balance your cheque books without the aid of calculators.

10) be Sherlock Holmes for a day. Try to memorize all the number plates you see while driving to work. (As he would say “elimentary my dear Watson” )

11) Exercise everyday. Regular exercise like walking or running is good for the brain.

12) Sleep well at night for at least 8 hours.

13) Drink alcohol in moderation.

14) learn a new skill: learn how to swim, play golf, play tennis etc.

Happy neurobics everyone.

Personal Regards,

Nitin Sethi, MD

Tip of the tongue and “senior moments”: the truths behind dementia

Tip of the tongue and “senior moments”: the truths behind dementia

Nitin K Sethi, MD


        Comprehensive Epilepsy Center, Department of Neurology, NYP-Weill Cornell Medical Center, New York, NY (U.S.A.)


Address for Correspondence:

NK Sethi, MD

Comprehensive Epilepsy Center

Department of Neurology

NYP-Weill Cornell Medical Center

525 East 68th Street, York Avenue

New York, NY 10021

Fax: 212-746-8984


I read an interesting article in the Wall Street Journal by Melinda Beck titled ” The science behind senior moments”. In it she talks about “senior moments”-episodes where-in you are temporarily unable to recall a name, forget a number (like the telephone number of a close friend or a relative) or enter a room and forget what you were supposed to do. Just what do these “senior moments” represent-are they just signs of normal aging process or are they a warning sign of impending dementia?

Let me give you an example. Let us assume you are watching a movie starring Cary Grant. You see Cary Grant on the screen, you know who he is but for the life of you, you cannot recall his name. we call this the “tip of the tongue” syndrome. You have the name on the tip of your tongue but are unable to get it out. We all have older family members and friends. We notice that at times they are more forgetful. They forget their keys, forget names: are these “senior moments” or are they signs of dementia? Is there anything called senile dementia? (that is dementia occuring due to old age itself, not due to a neurodegenerative condition like Alzheimer’s disease).

Before we discuss this further, we should try to understand how memories are formed and stored in the brain. In simple terms we first register and encode memory, then this is stored and finally it is retrieved. What do i mean by this? Well the first thing which occurs is registration and encoding. For one to retain memory, one must first register what one is trying to remember. Let me explain this with an example. Lets assume you are reading a book. At the same time you are watching the TV and talking to your friend on the phone (that is you are multi-tasking). Now if I ask you to recall what you just read, it is possible that you shall not be able to do so well. Why? This is because your attention was divided and hence you never really registered what you were reading in the first place. If you did not register, you did not commit it to your memory and hence you cannot recall it. So first lession is that when you are trying to memorize something, make sure you pay attention.

Then comes consolidation and storage of memory, the process by which the brain stores the memory. Memory is usually stored in the temporal lobes and the hippocampus. This is a complex process and a lot is still not known how exactly are these memory programs laid down in the brain. Consolidation and storage of memory ensures that the memories become more permanent. There is some data to suggest that consolidation and storage of memory occurs at night while we are asleep. Maybe there is some truth to grandma’s saying of getting a good night sleep before a big examination.

Finally is the process of retrieval. This is the process by which we are able to recall an old memory. One can have a problem at any step of this memory process. Patient’s with Alzheimer’s dementia usually have a problem with both consolidation and retreival. Someone who is intoxicated but does not have Alzhemier’s dementia like an alcoholic shall have problems with encoding as he is delirious.

Now that we know how memory is formed, I want to stress that the tip of the tongue syndrome occurs in many healthy people. Why does it occur? Why is there a temporary memory block which then clears by itself and we are able to remember everything? No one quite knows the answers to these questions.

Senior moments though (especially if they are occuring in the senior population above the age of 65) deserve a more closer look. Is the problem episodic (comes and goes) or is it constant (always present)? Is is static and stable or is it progressive? Does it involve just one domain of memory (like names) or is it more widespread involving multiple domains (not just names but things like forgetting how to drive a car, problems with calculations and abstract thinking etc).

If the above are present, then it is not senior moments and is more likely to be dementia. Some neurologists doubt if something like senile dementia actually exists. We all have met some elderly people with razor sharp memory.

That in essence is the truth behind senior moments and the tip of the tongue syndrome.