What is dementia?

In this post, I provide information on the group of diseases that fall under the umbrella of Dementia, focusing on treatment options to manage them.

Before we begin discussing Dementia and associated drug therapy, we must review and understand some basic definitions as they relate to this topic:

Definitions Related to Dementia

Neurodegenerative Diseases

Occur when nerve cells or tissue in the brain begin dying off slowly over time.

With this type of disease, there is no known cure or path to slowing the progression of the disease.

Cognitive Decline or Impairment

This occurs when an individual has trouble remembering, concentrating, making decisions, or learning new things that affect their daily life.

Cognitive impairment can range from mild to severe.

Cognitive impairment is usually attributed to older adults in some stage of dementia or other neurodegenerative diseases such as Parkinson’s or Huntington’s.

It can also be associated with people suffering from certain types of traumatic brain injury.

Prevalence

According to the National Institute of Mental Health, prevalence is the proportion of a population who has a specific disease in a given period, regardless of when they first developed the disease.

An example statement would be, “5.8 million Americans currently live with Alzheimer’s and other related dementias.”

Incidence

This measures the number of new disease cases that develop in a population within a specific period.

An example statement would be, “500,000 new cases of dementia will be diagnosed in 2020.”

Activities of Daily Living​ (ADLs)

Basic self-care tasks that all of us do, learned from early childhood.

Examples are toileting, bathing, brushing teeth, putting on clothes, etc​.

Instrumental Activities of Daily Living (IADLs)

These tasks require more complex thinking but are essential for living independently. We do these tasks without giving them a second thought.

Still, older people struggling with memory problems and declining mental abilities struggle incredibly with these.

Examples are balancing checkbooks, paying bills, managing medications, planning alternate routes while driving, etc.​

Aphasia

Impairment of one’s ability to communicate. Affects speech as well as the written language. Many sub-types exist.

All of this is covered in my book and course.

Apraxia

Inability to carry out a learned motor task, such as placing a fork in one’s mouth, even though they fully understand the request.

Agnosia

Failure to recognize or identify objects despite intact sensory function.

What is Dementia?

Dementia is a general term that describes a family of neurodegenerative diseases that inevitably cause a continued decline in memory and cognitive function.

This terrible disease affects older adults and their loved ones, caregivers, and friends.

I can’t imagine anything worse than someone losing everything that makes them the unique individual they are.

Alzheimer’s Disease is a type of dementia and is the most common form of this family of cognitive disorders.

Other types of diseases in this group are Vascular Dementia, Lewy Body Dementia, Frontotemporal Dementia, and Parkinson’s Disease Dementia.

The vast majority of all dementia cases in the U.S. are diagnosed as Alzheimer’s Dementia, with a prevalence between 60-80% of all diagnosed cases.

The table below describes the different types of dementia and provides statistical information on the overall sufferers of these diseases.

 

Different Types of Dementia

Type of Dementia	Prevalence*	Clinical Features	Comments
Alzheimer’s Disease (AD)	60-90% of dementia cases	slow symptom onset; initial forgetfulness progressing to profound memory loss with one or more of: aphasia, apraxia, agnosia, or impaired executive function	Symptoms generally begin after age 60. May coexist with vascular dementia (mixed- picture dementia)
Vascular Dementia (VD)	Population prevalence: 2 out of every 1000 people (age 65-70) to 16 out of every 100 people (age 80 and older)	Stepwise rather than gradual deterioration; problem with vision, speech, hearing, walking; rapid, uncontrolled emotional changes; impaired judgment	Sudden decline usually indicates a stroke. Progressive small vessel damage (from uncontrolled diabetes/high blood pressure) in the deepest part of the brain may cause slow progression
Lewy body disease (LBD)	2% - 30% of dementia cases	Involves any 2 of the following: visual hallucinations, parkinsonism or repeated unexplained falls, and fluctuation in mental state in the absence of delirium.	Earlier age of onset than either AD or VD. Cognitive impairment affects both memory and ability to carry out complex tasks and can fluctuate within 1 day, so may be confused with delirium.
Parkinson’s Disease dementia (PDD)	In people with PD, as many as 75% will develop PDD sometime in the course of their disease.	Diagnosis of PDD may be difficult as there is often overlap with AD, VD, and DLB. In PDD, parkinsonism is usually diagnosed years before dementia.	Older age and the severity of parkinsonism are risk factors for the development of PDD.
Frontotemporal dementia (FTD)	2-10 cases per 100,000 in general population	Personality changes, mood fluctuation, and alterations in behavior (such as disinhibition and lack of insight – socially inappropriate behavior). May be difficult to differentiate from bipolar disorder.	Anger, apathy and social withdrawal may make it difficult to differentiate from depression.
Traumatic Brain Injury (TBI)	1.7 million instances of TBI annually. ~2% of US population lives with TBI-associated disability	Course of recovery from TBI is variable depending on specifics of injury and other factors such as age, previous injury, and substance abuse	Severity of the TBI itself may not correspond to severity of the resulting neurocognitive disability (severity of the brain injury does not equal the level of mental disability).

*Prevalence figures do not sum to 100% because of the wide variability in prevalence estimates and the possibility that patients may experience more than one type of
dementia simultaneously
Credit: Management of the behavioral and psychological symptoms of dementia, National Resource Center for Academic Detailing, 2013. Data sourced from DSM-5,
Diagnostic and Statistical Manual of Mental Disorders: Fifth ed. Washington DC: American Psychiatric Association; 2013.

What are the Signs and Symptoms of Dementia?

The Alzheimer’s Association states that the following are the ten most common warning signs and symptoms of dementia:

• Sign 1: Memory loss affecting one’s ability to conduct daily activities, such as constantly repeating the same questions over and over
• Sign 2: Experiencing difficulty with IADLs (missing monthly bills, etc.)
• Sign 3: Difficulty with completing familiar tasks, such as forgetting a driving route that one has driven for years
• Sign 4: Confusion with location or time, such as forgetting the year or month or confusing the seasons
• Sign 5: Trouble understanding visual-spatial relationships, such as not comprehending that an oncoming car is too close and driving out onto its path, causing the other driver to slam on their brakes or veer dangerously to oncoming traffic or a ditch to avoid colliding with the cognitively impaired person.
• Sign 6: Difficulty with the written or spoken word. Impaired individuals will struggle with word-finding or stopping mid-sentence, not knowing how to proceed.
• Sign 7: Constantly losing things because they have forgotten where they had placed the items.
• Sign 8: Increasing instances of poor decision-making, such as giving away money to strangers or scammers on the phone or not maintaining proper toileting hygiene
• Sign 9: Social withdrawal due to inability to hold or follow conversations.
• Sign 10: Mood or Personality changes, manifesting as unfounded suspicion of other’s/loved ones’ motives, anxiety, depression, or confusion.

If you notice any of these signs in your loved one, it is best to have them evaluated by a qualified doctor as soon as possible.

What Causes Alzheimer’s Disease/Dementia?

It is important to remember that there might be other medical or medication causes contributing to your loved one’s behavior and not assume that they may have dementia.

Some of the causes of these dementia-like symptoms can be reversible.

Several risk factors are associated with an increased risk of developing dementia.

Some of these risks are modifiable, meaning we can control them, while others are non-modifiable, meaning we have no control over them.

Listed below are examples of these risk factors:

 

Modifiable and Non-Modifiable Risk Factors of Dementia
Modifiable Risk Factors:
Medication adverse effects​	Obesity​	Poor nutrition​	Risk factors for vascular disease​	Hypertension​
High Cholesterol	Cerebrovascular disease​	Diabetes mellitus and insulin resistance​	Sleep apnea​	Dehydration​
Thyroid, kidney, or liver disorders​	Behavioral health​	Depression	Stress	Traumatic Brain Injury
Substance Use/Abuse	Smoking	Alcohol abuse
Non-Modifiable Risk Factors:
Age	Sex	Family History	Genetic predisposition

 

Test your knowledge about risk factors:

A 59-year-old female has a strong family history of Alzheimer’s disease.

She would like to reduce her risk of developing symptoms of dementia.

Her current medical conditions include diabetes mellitus type 2, hyperlipidemia, gout, hypothyroidism, and psoriasis.

Her risk may be reduced by optimizing the therapy of which of the following conditions?

A. Gout and psoriasis

B. Gout and diabetes

C. Psoriasis and diabetes

D. Diabetes and high cholesterol

DON’T LOOK AHEAD FOR THE ANSWERS! TAKE A FEW SECONDS TO REVIEW YOUR OPTIONS AND COME UP WITH YOUR ANSWER…GOOD? OK, LET’S REVIEW OUR ANSWER BELOW:

 

If we apply the knowledge we have gained from reviewing the content in the table above, we can confidently eliminate option A.

Neither Gout nor Psoriasis are cardiovascular risk factors for dementia. Answer A is incorrect.

Answer B does have a risk factor, diabetes. However, Gout is not. So, Answer B is incorrect.

Likewise, only one of answer C’s options is a known risk factor. Answer C is also incorrect.

The clear answer is D, because Diabetes and High Cholesterol are known cardiovascular risk factors for dementia.

Years of poorly controlled high cholesterol and diabetes can slowly damage the blood vessels feeding vital blood, oxygen, and nutrients to the brain, resulting in the development of dementia.

What are the Stages of Dementia?

It is important to note that dementia begins well before signs and symptoms slowly manifest.

Cognitive decline begins long before the diagnosis of dementia.

It is widely accepted among clinicians and geriatric specialists that there are three stages in the development and progression of Alzheimer’s disease.

The pre-clinical or “silent” phase

The damage is already beginning to happen in the brain by accumulating amyloid plaques and neurofibrillary tangles.

No noticeable changes in the individual are observed, but the person knows that something is “off” about their cognition.

This phase can begin decades before others notice cognitive changes.

Mild Cognitive Impairment

In this stage, symptoms become noticeable to loved ones and the affected individual.

The impairment is significant but not severe enough to interfere with daily activities.

However, IADLs have become increasingly challenging to manage.

MCI refers to abnormal memory complaints for age and educational background but does not meet the criteria for dementia.

Individuals with MCI have a 2.8-fold increased risk of developing Alzheimer’s Disease, with about 10-15% of those with MCI developing Alzheimer’s every year.​

Evidence supports that not all people diagnosed with MCI will progress to dementia.

Dementia

There is a significant decline in cognitive abilities, memory, and functional status in this final stage.

Within the stage of dementia, there are gradations as well, ranging from mild, moderate, moderately severe, to severe.

The diagram below describes the three stages visually:

 

What Treatment is Available for Dementia?

It is important to note that nonpharmacologic and pharmacologic strategies for managing dementia and its associated behavioral and psychological symptoms (agitation, anxiety, wandering, hallucinations, etc.) have not been shown to change long-term outcomes.

Still, they are increasingly used to help maintain patient independence, improve quality of life, and reduce caregiver burden.

One of the essential tasks that a doctor or pharmacist can do is complete a thorough medication review of their patient.

When I begin reviewing a new patient’s chart, I take a very close look at every prescription medication, herbal, supplement, and over-the-counter drug my patient is taking.

In doing so, I am looking at everything –

• Is there a clear  medical need for every medication?
• Are the doses appropriate?
• Is my patient tolerating all of their medications well?
• Side effects?
• Adverse effects?
• Are drug interactions present?
• If so, what are they?
• Is my patient a candidate for drug therapy with any cognitive enhancers such as Aricept?
• If so, have I assessed all of their clinical status to ensure that the Aricept is not going to cause them harm?
• What is the follow-up and monitoring plan moving forward?
• Does my patient know who to call, when to call, and what to say?
• Am I adding to polypharmacy or unnecessary pill burden for my patient?

These are just some of the questions my geriatrician colleagues and I ask when assessing our patients.

Medication Management of Dementia: The Cholinesterase (or Acetylcholinesterase) Inhibitors and the NMDA Antagonist

Let’s look at some of the common medications that are used to treat dementia:

There are two medication classes available – The cholinesterase Inhibitors and the NMDA receptor antagonist.

It is important to note that neither class of medications alters the underlying medical reasons for dementia and will not reverse the progression of the disease.

In the cholinesterase inhibitor class of medications, three drugs are FDA-approved: Aricept (donepezil), Exelon (rivastigmine), and Razadyne (galantamine).

There is only one medication in the NMDA antagonist drug class, Namenda (memantine).

Cholinesterase Inhibitors are first-line agents for Alzheimer’s Disease and Dementia with Lewy Bodies.

They can also be used for Vascular Dementia and Parkinson’s Disease Dementia.

There isn’t much difference in terms of effectiveness between all three agents.

Below is a table detailing specific dosing for each of the approved medications:

 

Medications To Treat Dementia - Dosing Information

Drug	Starting Dose	Dose Increase Schedule
Donepezil (Aricept)	5 mg by mouth once daily	Increase to 10 mg once daily after 4-6 weeks according to response
Galantamine (Razadyne)	4 mg by mouth (immediate-release) twice daily 8 mg by mouth (extended-release) once daily	Increase by 8 mg/day (given in 2 divided doses) every 4 weeks according to response, maximum 24 mg/day Increase by 8 mg/day every 4 weeks, maximum 24 mg/day
Rivastigmine (Exelon) - oral Rivastigmine (Exelon) - skin patch	1.5 mg by mouth twice daily 4.6 mg/24 hour skin patch once daily	Increase by 3 mg/day (given in 2 divided doses) every 2 weeks according to response, maximum 12 mg/day Increase to 9.5 mg/24 hour patch once daily after 4 weeks according to response; starting dose varies if switching from oral to patch therapy​
Memantine (Namenda)	5 mg by mouth once daily	Increase by 5 mg/day every week to a target dose of 10 mg twice daily; give bid if dose > 5 mg per day​

 

As a general rule at my practice, our patients are prescribed these medications and are monitored for 6 to 12 months to determine if there’s any clinical benefit.

We will bring the patient back around that time and conduct another cognitive test and compare the results to that of the first test done at the time of diagnosis six months prior.

If it is determined that our patient’s cognitive decline is still happening, we will decide that it is not working and will more than likely stop the medication (termed lack of efficacy).

There’s also another scenario where the medication may work initially for the first few months, but at some point, it will start losing its effectiveness (termed loss of efficacy).

Again, it is essential to note that dementia is a progressive disease and cannot be reversed.

As such, all patients will at some point deteriorate clinically even though they may be on medications that seem to improve them initially.

Common side effects of acetylcholinesterase inhibitors:

• Nausea
• Vomiting
• Diarrhea
• Anorexia (loss of appetite)
• Bradycardia (slow heart rate)
• Syncope (fainting/loss of consciousness)
• Dizziness
• Headache
• Insomnia
• Vivid dreams

The side effects typically occur during the medication initiation or during a dose increase.

If the side effects become intolerable, your doctor might consider switching to another medication within the same drug class (cholinesterase inhibitors)

This drug class’s most common side effects are GI-related, specifically nausea and diarrhea.

Management of the Behavioral and Psychological Symptoms of Dementia (BPSD):

BPSD is a diverse constellation of symptoms, including:

• Calling out
• Screaming
• Verbal and physical aggression
• Agitation
• Hostility
• Sexual disinhibition
• Defiance
• Wandering
• Intrusiveness
• Repetitive behavior and or vocalizations
• Hoarding
• Nocturnal (nighttime) restlessness
• Psychosis (hallucinations or delusions)
• Emotional instability
• Paranoid behaviors

Over 90% of patients with dementia will experience at least one behavioral psychological symptom of dementia.

This can be highly distressing to caregivers and families and is a frequent cause of older adults being placed in institutional (long-term care) facilities.

These symptoms can be triggered by any change in environment, health, or social arrangements.

Behavioral Symptom Treatment:

Non-medication treatments are the cornerstone of the management of dementia.

Before medicating for behavioral symptoms, we must ensure that our loved ones are being treated for pain, anxiety, depression, constipation, incontinence, hunger, thirst, and infection.

When non-medication options have been exhausted, medication treatment should be warranted if a patient poses a danger to themselves or others.

The Food and Drug Administration (FDA) has not approved any medications specifically to manage BPSD.

Doctors prescribe off-label medications to help manage their patients’ dementia-associated behavioral problems.

In our practice, we are cautious about prescribing these agents because many of them cause serious side effects in our patients.

Medications to Avoid in Individuals with Dementia

For any non-emergency BPSD, two classes of medications must be avoided whenever possible:

• The benzodiazepines (e.g., Xanax or Valium)
• The antipsychotics (e.g., Seroquel)

The risks of being on these medications far outweigh any potential benefits.

There are many risks of putting your loved one on a benzodiazepine or an antipsychotic.

Specifically, cognitive impairment may be made worse with these medications.

Rebound insomnia can also happen, where their insomnia comes back with a vengeance.

These medications also put your loved one at risk for falls, fractures, and premature death.

If they are on the medication for a long time, they may become physically dependent on the drug.

A 2012 study found that during a 15-year follow-up period, new use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia in study participants.

The take-home message is that these medications are contraindicated in patients with dementia.

If these medications must be prescribed, then the golden rule of geriatric pharmacy must be followed: Start low, go slow.

If your loved one is prescribed an antipsychotic, they must be monitored closely for any adverse drug event or drug interactions with their current medications.

If there is no response to the medication, your loved one must be re-evaluated after three to six months of being on the drug.

This is because BPSD symptoms are inherently unstable and will wax and wane independently.

So, there may be a time when your loved one may not need the medication.

Under no circumstances should any of these medications be continued indefinitely.

Gradual dose reduction of the drug must be attempted regularly with the ultimate goal of discontinuing it.

Antipsychotic Serious Adverse Events

Antipsychotics can cause:

• Strokes
• Seizures
• Extrapyramidal side effects (which resembles Parkinsonian movement)
• Drowsiness
• Cognitive decline
• Confusion
• Increased risk of falls
• Tardive dyskinesia
• Social withdrawal
• Heart rhythm issues
• High blood glucose
• Postural hypotension (unsafe drop in blood pressure when standing up from a seated position)
• Angioedema
• Increased risk of premature death

In addition, older adults prescribed antipsychotics to control agitation or anxiety are at risk for adverse cardiovascular events within the first 30 days. This risk continues for up to three years after that.

Antipsychotic use in patients with dementia is associated with a 60 to 70% increased relative risk of death. It is highest in the first forty days of use, and the danger only increases with higher doses.

“Cognitive Enhancer” Supplements

A word of caution about supplements or cognitive enhancers that are now flooding the market and prime-time airwaves: these supplements are not based on evidence-based medicine, even though they claim scientific clinical trials back them.

None of them are FDA-approved and do not have oversight by governmental regulators.

Because of this, these supplement manufacturers don’t have to abide by safety standards and purity standards.

In other words, you have no idea what you’re putting inside your body. Some of them could prove to be extremely dangerous to your health.

At best, you lose a lot of your hard-earned money. At worst, you could end up in the hospital or even worse.

Each year in the United States, at least 23,000 emergency room visits can be traced to dietary supplements.

To learn more, read my in-depth articles on Prevagen and Neuriva.

Summary:

• The term Dementia is used to describe a family of neurodegenerative diseases that cause a continued decline in memory and cognitive function
• Alzheimer’s Disease is the most common cause of dementia
• Dementia cannot be reversed, but options are available to improve your loved one’s quality of life and autonomy
• The cholinesterase inhibitors and the NMDA antagonist are approved to treat dementia, but their risks outweigh any short-term benefits
• BPSD can be managed with antipsychotics, but only under certain circumstances and under the close oversight of the medical provider
• Antipsychotics use in patients with dementia has been associated with severe adverse effects and premature death
• Supplements purporting to help improve dementia-associated memory loss are dangerous and can result in hospitalizations