The other sides of Dementia,
away from Alzheimer’s disease.
Diagnosing Dementia and it type can be challenging. If we believe that people have Dementia when they start having cognitive impairment, loose their ability to perform their daily living abilities like paying their bills, driving safely or take their medication, we will have to recognize a pattern of loss of skills and functions to determine what the individual is still able to perform. Recently we have presented the way biomarkers have been used in the diagnosis of Alzheimer’s disease. I will refer you to the published AMHE Newsletter # 262 to review entirely the article on Alzheimer disease.
Dementia is a brain disease that causes a gradual decrease in the ability to think and remember, but in a long term, it impinges on the ability to function daily. Common symptoms can be emotional with difficulties in language and loss of motivation. Mainly, there is a change in the mental status.
In 2010, it was estimated that 35,6 million cases of dementia around the world. In 2015, 46,8 million. The number of people living with dementia is estimated to double every twenty years. 2/3 of individual with the disease live in low or middle income countries. Almost half of the new case of dementia occur in Asia followed by Europe (25%), Americas (18%) and Africa (8%). The older you become, the more you are prone to dementia.
Until the end of the 19th century, the term dementia carried a broader clinical concept including mental illness and psychosocial conditions, referring to anyone who has lost the ability to reason. Some has compared it to Psychosis or to any organic diseases like syphilis that destroyed the brain or to the changes of dementia seen with the old age with vascular problems. The Greek philosopher Pythagoras was the first we believe, to have used the term Dementia in the 7th century BC describing people of the old and advanced ages in their “Senium”, a period of mental and physical decay in the 70’s and 80’s where the “mind is reduced to the imbecility of the first epoch of infancy.” In 550 BC, the Athenian Poet Solon argued that man’s will might be invalidated if it exhibits loss of judgement due to advanced age. The Chinese also made allusion to that period in describing the senile as a “foolish old person”. Aristotle and Plato spoke about the mental decay of the advanced age, viewing it as an inevitable transition in the human being.
Byzantine physicians wrote of dementia and reported at least seven emperors whose lifespan may have exceeded 70 years displaying signs of cognitive decline. In Constantinople, special hospitals housed patients diagnosed with dementia or insanity but this rule did not apply to emperors. Little is recorded about dementia in the western world for nearly 1700 years. William Shakespeare made allusion to the loss of mental function in old age in plays like Hamlet or King Lear.
During the 19th century, the teaching in the medical world was that brain changes were due to cerebral arteriosclerosis but when in 1907, Alzheimer’s disease was described in a 50-year-old woman, this conception started to change. I will again refer you to the AMHE Newsletter # 262 dealing with the Alzheimer’s disease.
This point of view remains traditional until it was challenged in the 1960’s by the establishment of a link between neurodegenerative disease and the age-related cognitive decline. It was then admitted that vascular dementia was rarer than Alzheimer’s disease. The neurologist Robert Kaltman in 1976, has discussed the possibility that dementia may be often a mixture of both conditions. Dementia may have been rare then because few people at that time were living past 85, although more common in women. In the 21st century, other types of dementia were differentiated from Alzheimer’s disease and vascular dementias. Let us try to bring to our audience the different types of Dementia.
The most common is the Alzheimer disease which represent almost 70% of the dementia, but we have already covered it deeply. The next type is the Vascular type of Dementia (25%). In third, you will find the Dementia with the Lewy bodies (15%) and in fourth, it exists a Fronto-Temporal Dementia. Finally, Dementia can be encountered in a less common form, associated with diseases like Syphilis, HIV, Hydrocephalus or Parkinson’s disease. Many other diseases may have manifestations of dementia or pseudo-dementia. It is not always easy to differentiate a “true” dementia from a neurodegenerative disorder; it may be why some consider the term as such.
The diagnosis is generally based on history of the illness and cognitive testing like the “mini mental state examination” (MMSE) added to medical imaging and hematologic studies which are generally used to exclude other causes. Risk factors like High blood pressure, Diabetes Mellitus and Obesity may play a factor. There is no single test to help in the diagnosis.
A mental health specialist may determine whether depression or any other mental health conditions may have contributed to the diagnosis. A neurologist will evaluate memory, visual perception, attention, reflexes, problem-solving, language, motion and balance etc. Cognitive and neuropsychological tests will allow to evaluate the thinking or the “cognitive” function. Other tests will evaluate memory, orientation, reasoning, attention and judgement.
CT and MRI have been helpful in ruling out any evidence of stroke or bleeding, tumor or hydrocephalus. Finally, laboratory tests can detect a deficiency in B12 vitamin or an underactive thyroid gland. Even an infection can be ruled out through the analysis of the spinal fluid to look for inflammatory cells or specific markers for any neurodegenerative disease.
There is no known cure for any type of dementia but only ways in managing symptoms at time through medications like:
1- Cholinesterase inhibitors: Donepezil (Aricept), Rivastigmine (Exelon) and Galantamine (Razadyne) which are used to boost the chemical receptors involved in memory and judgement. As you will remember, they were primarily used in the treatment of Alzheimer’s disease but have been tried as well in vascular dementia and in dementia with Lewy bodies. These medications increase the concentration of Acetylcholine into the brain and bring also many side effects like nausea, vomiting and diarrhea and less commonly muscle cramps, bradycardia, with fainting, loss of appetite and sleep disturbances.
2- Memantine (Namenda) regulates the activity of glutamate. It is an MDA receptor antagonist
with small benefits acting on the receptors in the brain to promote learning and memory function. This drug is often used in addition of a cholinesterase inhibitor. People taking the Memantine may complain of dizziness. Glutamate is an excitatory neurotransmitter of the nervous system which can lead to cell death (excitotoxicity) by overproduction. No medication has resulted in lowering down the progression of any dementia. This is the first anti-influenza agent to act the same way than Glutamate does in producing side effects like hallucinations, confusions and dizziness.
3- Other medications to treat symptoms of depression or sleep disturbances or agitation and even Parkinson may be added to the regimen.
4- The overall benefit of all those medications may be minor. Cognitive and behavioral interventions have shown positive effects in educating and providing emotional support to the caregivers who often become as well affected. An exercise program for the daily living activities may be beneficial in improving symptoms. Occupational and Physical therapies can also prevent accidents like falls in managing behavior while the dementia progresses. Modifying the environment in reducing noise may help patient function better. Make sure to hide sharp objects like knifes or keys. A monitoring system can be useful while a patient is being taught easier tasks to avoid confusion. Engineering houses to fit the need of the one suffering from dementia, may become a way in the future to assure a protective environment for the one suffering as well as their caregivers.
Around 50 million people are affected by dementia which remain the most common cause of disability. The incidence increase with age: 3 % of people between the age of 65 and 75 will suffer from dementia, 10 % between the age of 75 and 85 and nearly half of the people above 85 will show signs of Dementia. In 2013, 1.8 million of death were recorded with this diagnosis. As the baby boomers are living older, dementia is seen more and more often, resulting in an economic burden of more than 600 billion a year. Often, patients are seen in their wheelchair, physically restrained or heavily medicated which bring concerns in the public opinion.
In the Alzheimer’s disease, we have seen a dramatic cognitive decline caused by the buildup of plaques in the brain as well as the twisted strand of proteins called “Tau” also referred as tangles in patients generally in the late 60’s, 70’s or 80’s. They have demonstrated difficulties in remembering names or conversations. As the disease progresses, they presented confusion, disorientation and difficulties in speaking, swallowing and walking. I will refer you again to the Newsletter # 262 for comparison.
Symptoms in other Dementia vary with the types or stages of the disease. The neuropsychiatric symptoms presented are behavioral and psychological affecting balance, tremor, eating and swallowing, speech and language, memory and visual perception, wondering and relentless. The psychological symptoms of dementia are agitation, depression, elated mood, apathy, irritability, illusions, changes in sleeping and appetite. They may demonstrate “catastrophic reactions” when crying or being angry suddenly.
In the first stage, signs and symptoms are subtle with mild cognitive impairment but 70% in this condition, will progress to dementia. They may face memory trouble in finding the words while they can still handle their daily living activities. The Mini Mental State Examination (MMSE) remains normal at 30%.
In the early stage, symptoms are more noticeable and may start to interfere with life. Tasks around the house and at work become more difficult and the MMSE drops between 20 and 25%. They start showing memory difficulties with word finding problems (anomia) and start losing their organizational skills (executive function). Once they are unable to handle their finance, things will become more problematic. Many experts will look for activities of the patient five to ten year prior to evaluating the condition. In Alzheimer, we remember well that one striking symptom was the “memory difficulty” while in other dementia, “word finding” become the striking sign.
In the middle stage, the MMSE scores between 6 and 17%, diagnosing a moderate Dementia. They may lose all abilities to solve problems and their social skills are definitely impaired. They are unable to function outside of their house and one should not be left alone. They begin to require assistance for personal care and hygiene.
In the late stage of dementia, they become completely dependent and need 24-hour supervision to ensure personal safety and basic needs. They can’t be left unsupervised because they may wander and fall without being able to recognize a danger. They may be incontinent and unable to recognize the need to use a bathroom. They will increasingly show inability to eat and swallow. They may need to be fed with food in puree in order to avoid choking but surely they will dependent. It may be difficult at that point to maintain their weight. Soon they will refuse to get out of bed in spite of assistance. They will stop recognizing more familiar faces at this late stage, or they will start having difficulties in their sleeping habits.
There are also reversible causes of Dementia like in Hypothyroidism, Vitamin B12 deficiency, Lyme Disease, Neurosyphilis etc. Many patients presenting with memory difficulties, hearing loss may also be associated with dementia.
The most common symptoms in Alzheimer’s (70%) are the short term memory loss with poor reasoning and judgement. They have a poor “insight”. The part of the brain most commonly involved is the “Hippocampus” as well as the temporal and Frontal lobes. I will refer you to the AMHE Newsletter # 262 to refresh your memory.
Vascular Dementia (20%) is caused by a disease or injury affecting the blood supply to the brain, like following repeated minor strokes. This is the second most common cause of dementia and many will present with a mixed form with Alzheimer’s’ disease. The symptoms are dependent of the localization of the stroke and the involvement of small or large vessels. They may present with difficulty walking or a change in the way to walk, difficulty with attention, planning and reasoning, mood changes with depression. Progressive dementia sets over time but injury can be localized in critical area of cognition like the Hippocampus or the Thalamus while leading to cognitive decline or memory loss although it may not be as apparent in the early stages. Patients may exhibit difficulties in decision making and organization or they may exhibit stroke-like symptoms including weakness or temporary paralysis on one side of the body. People who have vascular dementia tend to have risk factors like Tobacco use, High blood pressure, High cholesterol, Atrial Fibrillation, Diabetes Mellitus, previous Heart attack or Angina. Brain Scans may show evidence of multiple strokes at different locations.
In Dementia with Lewy bodies (DLB), the primary symptoms resemble to the visual hallucinations (people or animal) when they are about to fall asleep. Their dreams can also be violent and scary. These signs are seen in the younger people during their 50’s and may become a problem for the sleeping partner. They may present with periods of being alert or drowsy or fluctuating levels of confusion. Others may present signs of “Parkinsonism” with tremor, rigid muscles, and a face without emotion. They have also difficulties with attention, problems solving and planning and difficulty with visual-spatial field. Imaging studies are unable to determine the diagnosis but often a scan may show hypo-perfusion (SPECT) or hypo-metabolism (PET) in the Occipital lobe. They do have often the plaques and the tangles encountered in Alzheimer’s. Sometimes, it represents a mixed dementia with crossover symptoms. Diagnosing a Dementia with Lewy bodies (DLB) is generally straightforward and rarely require imaging studies.
In Frontotemporal Dementia (FTD), there are drastic personality changes and language difficulties with early social withdrawal with behavior problems earlier in life. It is the most common type of dementia in people under 65. They exhibit an early lack of insight, act violently, dress strangely and become apathetic and anxious with trouble in communicating and language. Memory problems are not a striking finding. There are six (6) distinct variances:
a- The first type has major symptoms in personality and behavior resulting in poor hygiene. The patient becomes stubborn and refuses to acknowledge problems. He may socially withdraw from the social events eventually and will exhibit a loss of appetite. People suffering from this type of frontotemporal dementia may make inappropriate sexual comments or use pornography openly. The most common sign is Apathy.
b- A second type presents with an aphasia of the language which can be “semantic” with loss of meaning of words while it becomes difficult for them to name things. The patient can be asked to differentiate between an animal, a tree or any other object but become unable to pinpoint the object on the picture shown. In a third type, it is difficult to produce a speech in a primary progressive aphasia (non-fluent agrammatic variant). Patient may have trouble in finding the proper words because they have trouble in coordinating their facial muscles to speak. Finally, they can use only one word until they become completely mute.
c- Progressive Supranuclear Palsy (PSP) is another form characterized by difficulty in moving the eyes up and down (vertical gaze). Difficulty in moving the eyes upward maybe seen with aging but difficulty in moving eyes downward is a key sign in this form of Fronto-temporal dementia. Additional signs of depression, social withdrawal, apathy, progressive difficulty in eating and eventually in talking will appear with the progression of the disease. They develop also muscular rigidity, irritability and can occasionally be misdiagnosed for Parkinson’s. On scan study, the brain is generally shrinking (atrophic) with no other anomalies.
d- A dementia due to a Corticobasal Degeneration (CBD) is a rare form characterized by different types of neurological problems that progressively worsen while the brain is affected at different locations. Patient will show a common sign with difficulty in using one extremity. He develops an “alien limb” that seems to have a mind of its own. This limb moves without conscious control of the person’s brain. Simultaneously, jerky movements of other extremities can be noted (myoclonus), asymmetrically. Soon difficulty in speech from an inability to move the muscles of the mouth in a coordinated way, can be seen with numbness and tingling to the extremities. The person often neglects one side of the body for the one showing the problem. The affected extremity may be rigid and presents with muscle contractions causing dystonia (strange repetitive movements). On scan study, the corticobasal degeneration is often seen in the posterior aspect of the frontal and parietal lobes.
e- Finally, a frontotemporal dementia associated with Motor Neuron Disease (MND) showing disturbances in behavior, language and movement due to the death of the neurons.
Hydrocephalus represents rare cases of Dementia due to the build-up of fluid in the brain which can be drained surgically. Once treated, symptoms of memory loss, difficulty walking, poor bladder control can resolve.
Dementia with Parkinson’s disease presents troubles with movements control, tremors and balance. The disease affects an area of the brain rich in Dopamine producing neuron and may also present with Lewy bodies causing subsequent cognitive decline. 80% of people suffering from Parkinson will develop dementia in less than 20 years from the onset.
Dementia with Huntington’s disease is a progressive brain disorder characterized by involuntary movements and decline in reasoning and thinking skills. This disorder is caused by a gene defect that creates nerve abnormalities and breakdown early in the 30’s and 40’s.
In the Wernicke Korsakoff syndrome, the dementia is due to a severe Vitamin B1 deficiency seen in alcohol abuse. Patient will present with severe memory loss.
Creutzfeldt-Jacob disease (CJD) causes a dementia that worsens rapidly over weeks to months. This is a rare degenerative, fatal brain disorder affecting one (1) person on one million worldwide related to the Mad Cow disease. In the USA, around 350 cases are discovered each year, appearing in their 60’s with a rapid course of the disease. This disease was also discovered in people of an isolated tribe which practiced ritual cannibalism in Papua, New Guinea but may have almost disappeared by now. At the beginning, a failing memory with behavior changes, soon a lack of coordination and visual disturbances. As the disease progresses, mental deterioration, involuntary movements, blindness and weakness of the extremities will complicate the picture, until coma and death follow. This disease belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSE) or misfolded Prion diseases.
Dementia with Down Syndrome was already reported in the AMHE newsletter # 262, dealing with Alzheimer’s disease. Many people with Down syndrome will develop earlier sign of dementia but more related to Alzheimer’s once they get older. I on 3 in the 40’s and 2 on 3 persons in the 50’s with Down Syndrome, will develop Dementia. They carry the APP gene once they are born with an extra copy of the chromosome 21. Down Syndrome is a genetic disease because due to an abnormal gene acquired at the time of conception but not inherited. This gene tends to produce the specific “Amyloid Precursor Protein APP which lead to the buildup of protein clumps found in Alzheimer’s disease, called Beta amyloid plaques. By the age 49, almost all people with Down syndrome will develop those plaques along with the other deposits called “Tau Tangles” which interfere with brain function and produce the dementia. It is estimated that 50% of the patients with Down Syndrome may show such signs. This is no known parent to child transmission of the gene. Researchers are closely studying why only 50% will develop the symptoms.
Encephalopathy or Delirium may develop slowly and resemble to Dementia. Brain infection (viral encephalitis), subacute sclerosing pan-encephalitis, Whipple’s disease, Hashimoto’s encephalopathy, cerebral vasculitis, tumors such as lymphoma or glioma, drug toxicity (anti-convulsants), metabolic causes like in liver failure or kidney failure or chronic subdural hematoma can all show signs of Dementia.
Many other inflammatory conditions may affect the brain and the cognition including Behcet’s disease, Sarcoidosis, Sjogren’s syndrome, Systemic Lupus Erythematosus, celiac disease, but this type of dementia can vary from resembling to Alzheimer’s or Parkinson’s. So many diseases with heritable conditions can also cause dementia going to epilepsy, to Canavan disease, Sanfilippo syndrome to spinocerebellar ataxia etc… Depending on the syndrome, patients will develop a mild to a fixed or slowly progressive impairment with hearing loss, inability to ambulate or having control of the extremities. I would refer you to a neurologic textbook to review hundreds of diseases able to produce a dementia or a dementia like syndrome.
It is difficult to diagnose Dementia on symptoms alone. Brain scanning can help but in many cases, it may require a brain biopsy but it is almost never recommended by the clinician until it is discovered later at an autopsy. General screening for cognitive impairment or early diagnosing dementia have not shown to improve the outcomes. It was found that screening scans in people older than 65 with memory complaints to be helpful.
Symptoms must be present at least for six months to support a diagnosis of Dementia. Cognitive dysfunction (Delirium) can be confused with dementia. The delirium has a sudden onset and a short duration (hours to weeks) but simply related to a somatic disturbance. Some mental illness including depression and psychosis need to be differentiated from delirium or dementia or pseudo-dementia.
Various brief tests carry with them some liability:
1- The mini mental state examination (MMSE) already seen has the best potential to diagnose dementia if results are interpreted with an assessment of the person’s personality, their ability to perform activities of a daily living and their behavior.
2- The abbreviated mental test score (AMTS), the Modified Mini Mental State Examination (3MS), the Cognitive Abilities Screening Instrument (CASI), the trail-making test and the clock drawing test, the Montreal Cognitive Assessment (M0CA) all have been used to detect mild cognitive impairment. The M0CA was found to be superior to the MMSE. In anyway, education, age and ethnicity of the patient may affect the outcome of these tests.
3- Another approach to the screening for dementia is to ask for an informant to fill out a questionnaire about the everyday cognitive functioning of the individual to be examined.
Routine laboratory test and a full blood count to rule out underlying disease as well as B12 vitamin, Folic acid, Thyroid studies like TSH, C-reactive protein, Calcium, liver enzymes and renal function etc.
Imaging studies like CT scans or MRI are routinely performed although they do not depict any diffuse metabolic changes in persons associated with dementia nor any gross neurological problems such as paralysis or weakness. They may suggest internal pressure hydrocephalus or a stroke (infarction) that will point toward a vascular event. SPECT and PET are more useful in assessing long-standing cognitive dysfunction and have shown similar ability as a cognitive testing. The SPECT appears to be able to differentiate the vascular cause in multi-infarct dementia.
Recent researches have established the value of PET imaging used with “Carbon 11 Pittsburg Compound B” as a radiotracer (PIB-PET) in predictive diagnosis of Alzheimer’s. Studies reported that the radio tracer (PIB-PET) was 86 % accurate in predicting which patient with mild cognitive impairment would develop the disease within two years. Other radiotracer like the “Carbone 11 dihydro-tetrabenazine” (DTBZ) has led to more accurate diagnosis for more than ¼ of patients with mild dementia or mild cognitive impairment.
Maxime Coles MD
References:
1- Coles, M J-M: Alzheimer’s Disease, The Trademark of a Generation; AMHE Newsletter (262) pp 1-8.
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