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.


Not quite dementia? red flags to watch out for

Not quite dementia?  red flags to watch out for

Nitin K Sethi, MD

Assistant Professor of Neurology

New York-Presbyterian Hospital

Weill Cornell Medical Center

New York, NY 10065

I get many patients who tell me during their office visit that they are worried they may be getting dementia. The thought of Alzheimer’s disease with its progressive neurocognitive decline and memory loss is a frightening thought indeed and patients are justifiably worried.

SO LETS GET DOWN TO THE BASICS. What are the red flags/ warning sings that you indeed do have Alzheimer’s dementia starting off?

Patients who have Alzheimer’s dementia are usually not aware that they have a memory problem. In the initial stages of the disease, social graces are maintained. These early patients may be able to hold down a job, socialize with friends and no one is aware that they have a memory problem.  Small problems may be starting off though. Losing keys, misplacing things, having problems with numbers, having problems balancing the cheque books and in counting change, forgetting names etc. As you can imagine these are not “major issues” and may not be noticed by the patient or family initially.

So usually when a patient hinself comes to me and tells me, he feels he may be getting demented, I approach it with a healthy dose of skepticism. Most of the times these patients do not have dementia, rather they may be depressed. Depression at times can lead to dementia like symptoms with loss of energy and drive and feelings of self-doubt. It is hence sometimes referred to as pseudo-dementia. You treat their depression and the patient feels much better and the memory problems resolve.

But when the patient is brought to my attention by a family member with complaints of memory problems, getting lost in the neighbourhood, change in personality, becoming indifferent to his personal appearance and grooming, apathy and lost of interest in activities previously enjoyed, in such patients the possibility of dementia crosses my mind.

One must remember that in dementias like Alzheimer’s disease (there are many different types of dementia), the problem is not just with memory. Dementias like Alzheimer’s disease affect a range of neuro-cognitive abilities. Thes patients have problems with language (we call this aphasia–there are many different kinds of aphasia), calculation, ability to sustain attention, ability of abstract thinking, of planning for the future (what I shall do next week) and in executitive functioning. They also suffer from what we call apraxias. Let me explain what apraxia is. Lets assume I can button and unbutton my shirt. Now this is a learned act, which I learned as a small child. Now suppose I get demented. Even though I am not weak (meaning the strength in my arms is intact), I forget how to button and unbutton my shirt. This loss of ability to carry out learned tasks despite intact motor/ muscle strength is called apraxia. Patients who have Alzheimer’s dementia forget how to tie their shoes laces, how to drive a car, how to eat with a spoon and so on. Hence in a way they become totally dependent on care-givers for all activities of daily living. Memory loss is just a component of a much bigger problem. Even when it comes to memory, they have problems in short term memory (what they ate for breakfast, who is the current President elect, whom did he defeat in the elections etc),  long term memory (what is your name, your wife’s name, your child’s name, where you were born, what date) may remain intact in the initial stages of the disease.

 So watch out for the red flags, not everything is dementia!!!

Cannabis use in patients with multiple sclerosis

Just read a study in Neurology about the effects of marijuana in patients with multiple sclerosis. It seems that MS patients who smoke marijuana have more cognitive dysfunction and mood disorders as compared to MS patients that do not. MS patients may be smoking marijuana recreationally or they may be using it to get rid of tingling and other paraesthesias.

Multiple sclerosis itself causes cognitive problems and if patients smoke marijuana it seems they compound them. With the limited data available to us currently, it is probably wise that patients with multiple sclerosis avoid smoking marijuana.

Nitin Sethi, MD



In this section we shall discuss a little about dementia. Just what do we mean when we say a person has dementia?

Dementia is a disorder in which a person has cognitive impairments in multiple domains. Meaning a patient with dementia has problems with memory ( forgets things), language ( speech gets sparse and content/ vocabulary decreases), calculation (person loses the ability to calculate: subtract, multiply etc), and abstract thinking. Depending upon what part of the brain gets affected, a patient with dementia may have personality changes and problems with executive functions like planning and other goal directed actions. They may also experience what we neurologists refer to as apraxias. Apraxia is an inability to do a learned act (example you can tie your shoe laces, it is an act you learnt as a small child. Now assume you get demented, you lose the ability to tie your shoes laces even though you are not weak and have full strength in your arms and legs). Patients with dementia may exhibit various kinds of apraxias, as the disease evolves they become dependent on care-givers for nearly all activities of daily living: cannot drive, cannot tie their shoe laces, cannot feed themselves or take a shower on their own.

There are many different types of dementia. These differ from each other in the cognitive domains affected and in the way they present clinically.

Classification of dementias:


1) Alzheimer’s dementia

2) Fronto-temporal dementia also referred to as Pick’s disease

3) Multi-infarct dementia also called vascular dementia

4) Dementia associated with Parkinson’s disease also called Parkinson’s disease dementia

5) Diffuse Lewy Body dementia

6) Primary Progressive Aphasia

7) AIDS dementia complex or HIV encephalopathy

8) Dementias associated with infections like syphilis

9) Reversible dementias like that due to hypothyroidism, deficiency of vitamin B12, thiamine (vitamin B1), hydrocephalus (normal pressure hydrocephalus)

10) Conditions which can mimic dementia example depression (pseudodementia)


Let us now discuss a few of these disorders. I shall start with the most common cause of dementia in the elderly namely Alzheimer’s dementia.


Alzheimer’s dementia: AD is the most common primary dementia seen in the elderly age-group. The onset of AD may be very subtle and frequently the care-givers or the patient cannot tell when did the disease first start. By the time the patients come to medical attention, the dementia is usually quite prominent. A point to note here, patients with dementia usually do not seek help by themselves. They do not feel anything is wrong with them, are not bothered by the lack of memory or their forgetfulness. It is their relatives and friends who first notice something is amiss. They notice that the patient keeps forgetting simple things, may get lost in their own neighbourhood ( for example the patient may not know what street he lives on and get lost while driving), other things like going to the grocery store and forgetting why one went there in the first place and having problems with names etc may be noticed.

Suprisingly in the earlier stages of the disease patients maintain their social graces pretty well. They may interact pretty gracefully in a social setting like a party or at work and if you are inter-acting with them casually you may never realise that they are having memory problems.

Diagnosing Alzheimer’s dementia: the diagnosis of Alzheimer’s disease is mostly clinical and a neurologist would be able to make the diagnosis clinically with a reasonable level of accuracy. Your doctor may order some tests like an MRI study of the brain and some blood tests to measure the thyroid hormone levels in your body, vitamin B12 level and also to rule out diseases which can mimic Alzheimer’s disease in its presentation such as syphilis. Nowdays more advanced imaging tests are been used to diagnose Alzheimer’s disease at an earlier stage of minimal cognitive impairment (MCI), these include PET (positron emission tomography) scan, SPECT (single photon emission computed tomography) scan and fMRI (functional MRI) scans. These facilities should be available in the big neurological centers.


Managament of Alzheimer’s Dementia: Alzheimer’s dementia is as of now incurable. However there are medications which can slow the progression of this neurodegenerative disease and improve the cognitive abilities of the patients. These drugs belong to a class of drug called cholinesterase inhibitors.  They inhibit the cholinesterase enzyme from breaking down acetylcholine, so increasing both the level and duration of action of the neurotransmitter  acetylcholine. Commonly prescribed drugs include: donepezil (Aricept), rivastigmine (Excelon), tacrine (tetrahydro aminoacridine) and galantamine. A few years ago, a new drug called memantine (Nemanda) was introduced into the market. This has a different mechanism of action as compared to the cholinesterase inhibitors. It is a NMDA receptor antagonist. Treatment with cholinesterase inhibitors does not alter the natural history of Alzheimer’s dementia. Patients though do get a few more months and possibly a few more years of relatively preserved cognitive abilities. Caregiver burden is reduced and patients may remain independent in some activities of daily living. Certain other medications and nutritional supplements have been advocated for Alzheimer’s disease patients with no proven efficacy. These include supplements like Ginkgo biloba and supratherapeutic doses of Vitamin E.

In the more advanced stages of the disease, patient’s become mute, akinetic (do not move spontaneously), they are incontinent, cannot feed themselves and become totally dependent on caregivers. Caregiver burn out is quite common and patients may be placed in nursing homes. In this advanced stage urinary tract infections (UTI), respiratory tract infections (pneumonias) and bed sores (decubitus ulcers) are common causes of morbidity and mortality. These advanced Alzheimer’s disease patients need good nursing care.


Let us talk a little about other neurodegenerative dementias. Fronto-temporal dementia also called Pick’s disease resembles Alzheimer’s disease except that these patients have early and more prominent frontal lobe involvement. Thus early on in the disease course, these patients have executive dysfunction (problems with planning things, thinking about future plans and how to go about making them happen). They also have prominent personality changes (may become angry, argumentative and suspicious) and also disinhibited (say whatever comes to mind, act inappropiately in social gatherings eg may start masturbating or touch themselves inappropiately).  The cholinesterase inhibitors used to treat Alzhemier’s dementia may also be tried in patient’s with fronto-temporal dementia (Pick’s disease). The name fronto-temporal dementia comes from the fact that these patients have prominent atrophy (decrease in mass or bulk or size) of the frontal and temporal poles/lobes.

Dementia of Lewy Bodies: is another type of dementia in which patient’s typically exhibit fluctuating symptoms. Visual hallucinations is a prominent component of this type of dementia. Patient’s respond poorly if medications like Haldol (haloperidol) are used to control their behavior. Atypical antipsychotics like Seroquel (quetiapine) are better drugs to control behavioral problems in these patients like agitation and aggression.

Dementia of Parkinson’s disease: Patient’s who have Parkinson disease may also develop dementia (memory problems) later on in their disease course. I shall discuss this further under Parkinson’s disease.

Depression or pseudodementia: Patients who have major depression may also look as if they are demented. These patients have anhedonia (no interest in any pleasurable activity like watching TV, getting a cup of coffee, watching a movie with friends). They just sit still, may not eat if not asked too and look akinetic. These depressed patient’s superfically may resemble dementia patients and hence depression is also referred to as pseudodementia. Once you treat their depression, they improve and all their “memory problems” go away.

Demented patients may have superimposed depression and vice versa hence a thorough search should be made to rule out depression in a patient with dementia as it is readily treatable.

I shall discuss depression under a separate heading. There are caretaker support groups for people who have loved ones suffering from dementia. They offer advice and help in preventing caretaker burnout.



A self realised man is one who controls his mind

Lord Krishna in the Bhagavad Gita


Depression is a relatively common neurological condition. It may occur on its own (as an episode of major depressive disorder or MDD) or it may occur during the course of another chronic neurological illness such as stroke. It is important that depression be recognized and treated since studies have shown that it increases the morbidity and mortality associated with these conditions.

Sometimes it is difficult to weed out which symptoms are due to depression and which due to the organic brain (neurological) condition. Patients who have fronto-temporal dementia (Pick’s disease), Parkinson’s disease, frontal lobe strokes may look depressed. They are akinetic (do not move spontaneously), have mask like emotionless faces and do not talk readily (abulia). On the first glance it may seem they have depression and not an organic neurological condition.

The point I am making is that depression may mask an underlying neurological condition like dementia or a frontal lobe tumor. The reverse is also true, people who have neurodegenerative conditions may have superimposed depression. Upon treating the depression they feel much better and may improve in caregivers rating scales.

The diagnosis of depression is essentially a clinical one. There are certain clinical features which if present for a sufficient length of time usually 2 weeks suffice to make a clinical diagnosis of major depressive disorder (MDD). These features include what is called anhedonia (loss of pleasure in day to day activities), depressed mood ( in children it may present as irritability), weight loss or weight gain, insomnia or hypersomnia (sleeping more than usual), changes in behavior and personality, feeling tired and fatigued, feeling of hopelessness and worthlessness and thoughts of death or sucide.

In a clear cut case no other investigations are warranted but like I stated earlier, at times some organic neurological conditions can present as depression. So to rule out secondary causes of depression, your doctor may order a MRI brain and tests like thyroid function tests (to check if your thyroid hormones are within the normal range–this is usually a simple blood test).

Treatment of depression: Treatment of depresion when it presents along or during the course of a neurodegenerative condition like dementia and Parkinson’s disease is essentially the same as treatment of idiopathic depression (depression which occurs without any organic cause). It involves using drugs. The most commonly prescribed drugs are those which belong to two classes:

1) Tricyclic antidepressants–drugs which belong to this class include medications like Elavil (amitriptyline) and  nortriptyline.

2) Selective Serotonin Reuptake Inhibitors (SSRIs)–drugs include Prozac (fluoxetine) and Paxil (paroxetine) among numerous others.

If a neurological condition is responsible for the depressive symptomatology. example a frontal lobe tumor then removal of that tumor or treatment of the underlying neurological condition is needed. Other treatments that may be attempted include CBT (cognitive behavioral therapy).

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