Dementia; Causes, Symptoms, Diagnosis, Treatment

Dementia is a broad category of brain diseases that cause a long-term and often gradual decrease in the ability to think and remember that is great enough to affect a person’s daily functioning. Other common symptoms include emotional problems, problems with language, and a decrease in motivation. A person’s consciousness is usually not affected. A dementia diagnosis requires a change from a person’s usual mental functioning and a greater decline than one would expect due to aging. These diseases also have a significant effect on a person’s caregivers.

Types of Dementia

There are several types of dementia, including:

• Alzheimer’s disease – is characterized by “plaques” between the dying cells in the brain and “tangles” within the cells (both are due to protein abnormalities). The brain tissue in a person with Alzheimer’s has progressively fewer nerve cells and connections, and the total brain size shrinks.
• Dementia with Lewy bodies – is a neurodegenerative condition linked to abnormal structures in the brain. The brain changes involve a protein called alpha-synuclein.
• Mixed dementia – refers to a diagnosis of two or three types occurring together. For instance, a person may show both Alzheimer’s disease and vascular dementia at the same time.
• Parkinson’s disease – is also marked by the presence of Lewy bodies. Although Parkinson’s is often considered a disorder of movement, it can also lead to dementia symptoms.
• Huntington’s disease – is characterized by specific types of uncontrolled movements but also includes dementia.
• Lewy body dementia/Lewy body disease – is caused by Lewy bodies, which are abnormal clumps of certain proteins, accumulating inside of neurons. Forgetfulness and other signs of cognitive decline are the primary features of this condition, but patients can also develop prominent hallucinations which seem very real to them. Some patients with Lewy body disease develop symptoms which look like Parkinson’s disease, such as tremor and slowness.
• Creutzfeldt-Jakob disease – is a rare condition where an abnormal protein leads to the destruction of brain cells and dementia. While most cases occur without an underlying cause, in some patients there is a family history of this disorder. Even less often, patients might be exposed to the abnormal protein. Mad cow disease is one example of external exposure. This condition tends to progress rapidly, over only a few years and is often associated with abnormal muscle movements.
• Mixed dementia – refers to patients who have evidence of two (or more) types of dementia. They are often described as having mixed dementia. Alzheimer’s disease and vascular dementia are the most common causes of mixed dementia.
• Normal pressure hydrocephalus – is an abnormal enlargement of the ventricles, or fluid-filled spaces within the brain, that causes pressure on areas of the brain. This leads to problems with walking, memory, and ability to control urine flow
• Huntington’s disease – causes characteristic abnormal movements, called chorea, in affected individuals. The movements are the hallmark of the diagnosis. However, in some cases, problems with memory can precede the development of the chorea by many years.
• Alcoholic dementia – is caused when patients drink heavily and develop a deficiency in one of the B vitamins. When this happens, brain cells are unable to function normally and memory loss can occur. This is called Korsakoff syndrome. Although it is most commonly seen in alcoholics, patients who are malnourished from other causes are also at risk of developing this disorder.
• Traumatic brain injury (concussion)/dementia pugilistica – can lead to memory problems, as we have learned in recent years. In some cases, recurrent brain injuries or repeated concussions can contribute to the underlying changes identified in Alzheimer’s disease.
• Dementias caused by other conditions – can lead to changes within the brain and associated cognitive decline. These include Parkinson’s disease, HIV (AIDS), multiple sclerosis, Wilson’s disease, meningitis (infection of the brain coverings), blood clots in the brain, and heart attacks. Some patients with brain tumors may develop memory problems which resemble dementia

Other disorders leading to symptoms of dementia include

• Frontotemporal dementia – also known as Pick’s disease.
• Normal pressure hydrocephalus – when excess cerebrospinal fluid accumulates in the brain.
• Posterior cortical atrophy – resembles changes seen in Alzheimer’s disease but in a different part of the brain.
• Down syndrome – increases the likelihood of young-onset Alzheimer’s.

Symptoms of Dementia

• Recent memory loss – a sign of this might be asking the same question repeatedly.
• Difficulty completing familiar tasks – for example, making a drink or cooking a meal.
• Problems communicating – difficulty with language; forgetting simple words or using the wrong ones.
• Disorientation – getting lost on a previously familiar street, for example.
• Problems with abstract thinking – for instance, dealing with money.
• Misplacing things – forgetting the location of everyday items such as keys, or wallets, for example.
• Mood changes – sudden and unexplained changes in outlook or disposition.
• Personality changes – perhaps becoming irritable, suspicious or fearful.
• Loss of initiative – showing less interest in starting something or going somewhere.

Stages of Dementia

• Mild cognitive impairment – Characterized by general forgetfulness. This affects many people as they age but it only progresses to dementia for some.
• Mild dementia- people with mild dementia will experience cognitive impairments that occasionally impact their daily life. Symptoms include memory loss, confusion, personality changes, getting lost, and difficulty in planning and carrying out tasks.
• Moderate dementia- daily life becomes more challenging, and the individual may need more help. Symptoms are similar to mild dementia but increased. Individuals may need help getting dressed and combing their hair. They may also show significant changes in personality; for instance, becoming suspicious or agitated for no reason. There are also likely to be sleep disturbances.
• Severe dementia – at this stage, symptoms have worsened considerably. There may be a loss of ability to communicate, and the individual might need full-time care. Simple tasks, such as sitting and holding one’s head up become impossible. Bladder control may be lost.

Treatment of Dementia

Most medications used to treat difficult behaviors fall into one of the following categories:

Antipsychotics

These are medications originally developed to treat schizophrenia and other illnesses featuring psychosis symptoms.

Commonly used drugs

• Risperidone 
• Quetiapine
• Olanzapine
• Haloperidol
• For a longer list of antipsychotics drugs,

Usual effects – Most antipsychotics are sedating and will calm agitation or aggression through these sedating effects. Antipsychotics may also reduce true psychosis symptoms, such as delusions, hallucinations, or paranoid beliefs, but it’s rare for them to completely correct these in people with dementia.

Risks of use 

The risks of antipsychotics are related to how high the dose is, and include:

• Decreased cognitive function, and possible acceleration of cognitive decline
• Increased risk of falls
• Increased risk of stroke and of death; this has been estimated as an increased absolute risk of 1-4%
• A risk of side-effects known as “extrapyramidal symptoms,” which include stiffness and tremor similar to Parkinson’s disease, as well as a variety of other muscle coordination problems
• People with Lewy-body dementia or a history of Parkinsonism may be especially sensitive to antipsychotic side-effects; in such people, quetiapine is considered the safest choice

Evidence of clinical efficacy – Clinical trials often find a small improvement in symptoms. However, this is offset by frequent side-effects. Studies have also repeatedly found that using antipsychotics in older people with dementia is associated with a higher risk of stroke and of death.

Benzodiazepines – This is a category of medication that relaxes people fairly quickly. So these drugs are used for anxiety, for panic attacks, for sedation, and to treat insomnia. They can easily become habit-forming.

Commonly used drugs

• Lorazepam (brand name Ativan)
• Temazepam (brand name Restoril)
• Diazepam (brand name Valium)
• Alprazolam (brand name Xanax)

Usual effects – In the brain, benzodiazepines act similarly to alcohol, and they usually cause relaxation and sedation. Benzodiazepines vary in how long they last in the body: alprazolam is considered short-acting whereas diazepam is very long-acting.

Risks of use 

A major risk of these medications is that in people of all ages, they can easily cause both physical and psychological dependence. Additional risks that get worse in older adults include:

• Increased risk of falls
• Paradoxical agitation (some older adults become disinhibited or otherwise become more restless when given these drugs)
• Increased confusion
• Causing or worsening delirium
• Possible acceleration of cognitive decline

Stopping benzodiazepines suddenly can provoke life-threatening withdrawal symptoms, so medical supervision is mandatory when reducing this type of medication.

• Evidence of clinical efficacy – A recent review of clinical research concluded there is “limited evidence for clinical efficacy.” Although these drugs do have a noticeable effect when they are used, it’s not clear that they overall improve agitation and difficult behaviors in most people. It is also not clear that they work better than antipsychotics, for longer-term management of behavior problems.
• Mood-stabilizers – These include medications otherwise used for seizures. They generally reduce the “excitability” of brain cells.
• Commonly used drugs – Valproic acid (brand name Depakote) is the most commonly used medication of this type, in older adults with dementia. It is available in short- and long-acting formulations.
• Usual effects – The effect varies depending on the dose and the individual. It can be sedating.

Risks of use

 Valproic acid requires periodic monitoring of blood levels. Even when the blood level is considered within an acceptable range, side-effects in older adults are common and include:

• Confusion or worsened thinking
• Dizziness
• Difficulty walking or balancing
• Tremor and development of other Parkinsonism symptoms
• Gastrointestinal symptoms including nausea, vomiting, and/or diarrhea

Evidence of clinical efficacy

A review of randomized trials of valproate for agitation in dementia found no evidence of clinical efficacy, and described the rate of adverse effects as “unacceptable.” Despite this, some geriatric psychiatrists and other experts feel that valproate works well to improve behavior in certain people with dementia.

Anti-depressants  – Many of these have anti-anxiety benefits. However, they take weeks or even months to reach their full effect on depression or anxiety symptoms.

Commonly used drugs

Antidepressants often used in older people with dementia include

• Selective serotonin reuptake inhibitor (SSRI) antidepressants Citalopram, escitalopram, and sertraline (brand names Celexa, Lexapro, and Zoloft, respectively) are often used in Paroxetine (brand name Paxil) is another often-used SSRI, but as it is much more anticholinergic than the other SSRIs, geriatricians would avoid this medication in a person with dementia
• Mirtazapine (brand name Remeron) is an antidepressant that can increase appetite and sometimes increases sleepiness when given at bedtime
• Trazodone (brand name Desyrel) is a weak antidepressant that is sedating and is often used at bedtime to help improve sleep

Usual effects

The effects of these medications on agitation are variable. SSRIs may help some individuals, but it usually takes weeks or longer to see an effect. For some people, a sedating antidepressant at bedtime can improve sleep and this may reduce daytime irritability.

Risks of use

The anti-depressants listed above are generally “well-tolerated” by older adults, especially when started at low doses and with slow increases as needed. Risks and side-effects include:

• Nausea and gastrointestinal distress, especially when first starting or increasing doses (SSRIs)
• SSRIs may be activating in some people, which can worsen agitation or insomnia
• Citalopram (in doses higher than 20mg/day) can increase the risk of sudden cardiac arrest due to arrhythmia
• An increased risk of falls, especially with the more sedating antidepressants

Evidence of clinical efficacy

A 2014 randomized trial found that citalopram provided a modest improvement in neuropsychiatric symptoms; however, the dose used was 30mg/day, which has since been discouraged by the FDA. Otherwise, clinical studies find that antidepressants are not effective for reducing agitation.

Dementia drugs

These are the drugs FDA-approved to treat the memory and thinking problems associated with Alzheimer’s disease. In some patients, they seem to help with certain neuropsychiatric symptoms.

Practical tips on medications to manage difficult behaviors in dementia

You may be now wondering just how doctors are supposed to manage medications for difficult dementia behaviors.

Here are the key points that I usually share with families

• Before resorting to medication: it’s essential to try to identify what is triggering/worsening the behavior, and it’s important to try non-drug approaches, including exercise. Be sure to consider treating possible pain or constipation, as these are easily overlooked in people with dementia. Geriatricians often try scheduling acetaminophen 2-3 times daily, since people with dementia may not be able to articulate their pain. We also titrate laxatives to aim for a soft bowel movement every 1-2 days.

• No type of medication has been clinically shown to improve behavior for most people with dementia. If you try medication for this purpose, you should be prepared to do some trial-and-error, and it’s essential to carefully monitor how well the medication is working and what side-effects may be happening.

• Antipsychotics and benzodiazepines work fairly quickly, but most of the time they are working through sedation and chemical restraint. They tend to cloud thinking further. It is important to use the lowest possible dose of these medications.

• Benzodiazepines probably increase fall risk more than antipsychotics do, and are habit forming. They are also less likely to help with hallucinations, delusions, and paranoia. For these reasons, if a faster-acting medication is needed, geriatricians usually prefer antipsychotics to benzodiazepines.

• Antidepressants take a while to work, but are generally well-tolerated. Geriatricians often try escitalopram or citalopram in people with dementia.

• It is usually worth trying a dementia drug (such as a cholinesterase inhibitor or memantine) if the person is not already on these medications, as these drugs also tend to be well tolerated.

I admit that although studies find that non-drug methods are effective in improving dementia behaviors, it’s often challenging to implement them.

As for residential facilities for people with Alzheimer’s and other dementias, they vary in how well their staff are trained in non-drug approaches.

What you can do about medications and difficult dementia behaviors

If your relative with dementia is not yet taking medications for behaviors, consider these tips

• Start keeping a journal and learn to identify triggers of difficult behaviors. You will need to observe the person carefully. Your journaling will come in handy later if you start medications, as this will help you monitor for benefit and side-effects.

• Learn to redirect and de-escalate difficult dementia behaviors. Contact your local Alzheimer’s Association chapter or local Area Agency on Aging to find support near year.

• Ask your doctor to help assess for pain and/or constipation. Consider a trial of scheduled acetaminophen, and see if this helps.

• Consider the possibility of depression. Consider a trial of escitalopram or a related antidepressant, but realize any effect will take weeks to appear.

If the person is often very agitated, or very paranoid, or if otherwise, the behavioral symptoms are causing significant distress to the older person or to caregivers, it’s often reasonable to try an antipsychotic.

• Be sure to discuss the increased risk of stroke and death with the doctor and among family members. This can be a reasonable risk to accept, but it’s essential to be informed before proceeding.
• It’s best to start with the lowest dose possible.
• If there have been visual hallucinations or other signs of possible Lewy-Body dementia, quetiapine is usually the safest first choice.

For all medications for dementia behaviors:

• Monitor carefully for evidence of improvement and for signs of side-effects.
• Doses should be increased a little bit at a time.
• Especially for antipsychotics, the goal is to find the minimum necessary dose to keep behavior manageable.

References