Keeping One's Head
Dementia and depression among the elderly
SUNLY
COO, CONTRIBUTING WRITER "People tend to think the onset of dementia deprives you of everything, that you are lost. That's not true. I wanted to send the message that I am getting on with my life, just like normal. My brain may be failing but I won't be alone. I will continue to try and live out my life my own way."
-Mr. Ochi, 73 years old, speaking in Kyoto of his dementia diagnosis, from Dementia in the Asia-Pacific Region: The Epidemic Is Here
It wasn't long ago when Filipinos believed that Alzheimer was a "Western" disease, a remote medical tragedy that hardly touched us, much less warranted our concern. Unlike diabetes, cancer, or cardiovascular diseases, from which a family, a friend, or a friend of a friend might have suffered, Alzheimer claimed no one we knew. It was not even mentioned, except in books and movies. But now, this disease is about to become a buzzword, as more and more populations, including Filipinos, are living longer. Alzheimer disease (AD) poses a very clear and present danger.
Globally, AD is the leading cause of dementia, a collective term for neuropathological symptoms characterized by significant cognitive impairment that interferes with daily functioning. In the Philippines, the estimated prevalence and incidence of dementia stand at 169,800 and 54,800, respectively, according to the landmark report Dementia in the Asia-Pacific Region: The Epidemic Is Here, released in September 2006. The numbers will rise significantly over the following years, as average life span increases, since old age is a strong risk factor for the disease. In fact, some experts believe that everyone, when given the opportunity to grow old, will eventually be afflicted with dementia. According to the report, Asia-Pacific countries will experience a staggering jump in the number of dementia cases, from 13.7 million in 2005 to 64.6 million by 2050.
Impaired functioning
Triggered by brain damage, dementia is not a specific disease, but a set of symptoms that express significantly impaired intellectual functioning. Patients experience a deterioration in memory, problem-solving skills, abstract thinking, and learning ability, and may even undergo personality changes and unexplained mood swings. In more severe cases, behavioral problems such as delusions, hallucinations, and violence result. As dementia progresses, performing normal daily activities become more difficult, leading to increased risk of injury for the patient and the people around him.
Various disorders cause dementia. Topping the list is AD, which accounts for about 60 to 65 percent of dementia cases worldwide, followed by vascular dementia at 20 to 30 percent. Rates of prevalence may vary from region to region and from country to country. Says Dr. Simeon Marasigan, president of the Dementia Society of the Philippines (DSP): "There are some indications that in most of the Asian countries vascular dementia may be more prevalent than Alzheimer disease. Maybe in Taiwan, China, and probably the Philippines, but we don't have credible statistics for that. My basis is that if you go by hospital admissions, clearly now for the past several years, [AD is] predominantly secondary to stroke [-induced dementia]-70 to 80 percent of admissions in both private and government hospitals. The statistics tell us that within the first year after stroke, probably about 15 to 20 percent of patients would develop vascular dementia."
AD and vascular dementia commonly strike after the age of 65, the risks rising with advancing age. While AD is a progressive disease that has no cure and neither can be stopped, some types of vascular dementia can be halted or reversed with proper treatment.
Failing memory
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It usually begins with a failing memory, from forgetting names to misplacing things, which may be normal age-related conditions. In people with AD, the gradual memory decline persists until they cannot recall recent memories, basic mathematical applications like subtraction, how to operate common household items, familiar words such as names of everyday objects, and personal information like one's address or the name of one's spouse. Patients can also get disoriented with time and place, and display gross lapses in judgment. According to a 2001 study, other neuropsychiatric symptoms and their prevalence among AD patients include agitation (60 to 70 percent), apathy (60 to 70 percent), depression (50 percent), anxiety (50 percent), irritability (50 percent), delusional disorders and psychosis (40 to 50 percent), disinhibition (30 percent), and hallucinations (10 percent). To track the pattern of the disease, the Seven Stages of AD was created based on a system developed by Dr. Barry Reisberg, clinical director of the New York University School of Medicine's Silberstein Aging and Dementia Research Center. It should be noted though that not every patient will experience all of the symptoms in each stage.
When patients reach the waning years of the disease, they become incapacitated such that performing daily functions, like eating or using the toilet, requires assistance. They may eventually lose their reflexes, including the ability to swallow, a condition that makes them susceptible to aspiration pneumonia, which often causes death among AD patients.
Once diagnosed, patients live up to eight years on average. However, the time span can be anywhere from three to 20 years. In the Philippines, patients often delay consulting a physician until the AD symptoms worsen. "Normally they come to us by the second stage of Alzheimer disease," Marasigan says.
Vascular anomalies
When dementia is caused by cerebrovascular and cardiovascular anomalies, such as stroke or heart attack, the symptoms often appear suddenly and conspicuously. But when the damage is in the midbrain regions, the mental decline may be gradual and progressive, similar to that of AD. Patients with vascular dementia also do not usually experience personality changes or frequent lack of emotional control, not until the later stages of the disease. And unlike AD, the symptoms might stabilize or even improve over time if no additional strokes occur and if proper treatment is received.
Among the different types of vascular dementia, multi-infarct dementia (MID) affects the most number of lives. MID is caused by a series of small strokes in the brain that are typically restricted to one side of the body or to areas of the brain controlling a specific function, such as language. In some cases, just one incident of stroke is enough to trigger what is known as single-infarct dementia. The disorder usually results when the stroke occurs on the brain's left hemisphere or the hippocampus.
To diagnose dementia, physicians review the patient's medical history and employ a battery of tests to rule out treatable causes. The work-up includes a physical examination, routine diagnostic tests, and a neurological evaluation that checks for sensory function, reflexes, coordination, and balance. Mental abilities-memory, language and math skills, and others-are screened through cognitive tests, like the mini-mental-state examination (MMSE) and the mini-COG. Because these tests are written in English-"Out of the 30 points, nine is dedicated to language," says Dr. Jacqueline Dominguez, vice president of DSP-their validity is questionable when they are administered to patients for whom English is not the primary language. As a solution, Dominguez formulated a Tagalog version of the MMSE, called MMSE-P, with a cutoff point at 23/24. She cautions: "When you get a score of 23 or below, it doesn't mean you have dementia, but you might possibly have it. This is only a screening tool."
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An essential part of the diagnostic process is a brain scan via magnetic resonance imaging (MRI) or computed tomography (CT). They detect structural changes, such as tumor, evidence of stroke, and a wrinkled brain surface caused by cortical atrophy, which is common in many dementia cases.
Risk factors
Age. AD, vascular dementia, and several other dementias commonly strike after the age of 65. Susceptibility increases with age, from 0.001 percent in people under 65, to one percent for people in their 60s, to almost 25 percent in individuals 85 and above.
Genetics/family history. Certain genes have been linked to dementia. The most widely recognized is a variation of a gene called apolipoprotein E (apoE). The variant, ApoE epsilon 4 (apoE E4), heightens the risk of late-onset forms of AD, and encourages deposits of amyloid in the brain. Researchers discovered that individuals with two copies of apoE E4 had 10 times the risk of acquiring AD compared with those without the gene variant. ApoE E4 is also linked to shorter survival in men with AD. Another variant, the apoE E2 gene, appears to guard the brain against the disease.
Mutations of three other genes in the brain are also believed to influence susceptibility to AD: amyloid precursor protein (APP), which is necessary for normal brain functioning and possibly a regulator of synapse formation; presenilin 1, which may be involved in producting and transporting proteins and regulating APP; and presenilin 2, whose function is unknown. The mutated version of another gene, CYP46, which normally creates a protein to help the brain metabolize cholesterol, may also boost the risk of developing late-onset sporadic AD.
Generally, having a family history of AD increases the chance of getting the disease, although there are many cases where individuals with such background never developed AD and those without family history did.
Gender. Women over 80 are at a slightly higher risk of AD, and by 93, the climbs to 93 percent, according to the Boston University School of Medicine Multi-Institutional Research in Alzheimer's Genetic Epidi-miology. Men, on the other hand, are more prone to vascular dementia.
Cerebro- and cardiovascular health risks. Smoking, excessive alcohol intake, high low-density-lipoprotein level, high blood pressure, diabetes, atherosclerosis, heart attacks, and strokes contribute to vascular dementia and AD. Most of these interrelated factors interfere with blood flow to the brain, causing brain-tissue necrosis. In the case of alcohol, some studies suggest that moderate drinkers are less likely to develop dementia than heavy drinkers and nondrinkers.
Plasma homocysteine. Having a high blood level of homocysteine, a type of amino acid, multiplies the risk for AD by three and vascular dementia by five.
Mild cognitive impairment. Not all who are diagnosed with this condition develop dementia, but those who do face a higher risk of developing dementia, as one study uncovered. After tracking a group of people over 65 who had been diagnosed with mild cognitive impairment, the researchers found that 40 percent eventually had dementia within three years.
Prevention
Education and mental stimulation. Having formal education and constantly engaging in mentally stimulating activities appear to protect one against dementia, specifically AD, or delay the onset or progress of the disease. One research revealed that regardless of the number of beta-amyloid plaques and neurofibrillary tangles in the brain, mental decline is relatively less in people who had more years of formal schooling than those who had fewer. Experts speculate that education strengthened the networks of nerve cells, enabling the brain to function at some level despite the diseased cells. Mental exercises, such as playing sudoku or doing crosswords, playing chess, reading a book, and learning a new skill, such as painting, help keep the neurons active and less vulnerable to dementia. Marasigan adds: "We should let our older people be more independent. For example, if they want to buy something, you may accompany them, but let them do the buying."
Healthy diet and lifestyle. A strong correlation exists between the risk of vascular dementia and the risk factors for stroke, thus emphasizing the need to maintain normal levels of blood pressure, cholesterol, and glucose. One study showed that treating elevated blood pressure, specifically isolated systolic hypertension, in people aged 60 and above resulted in a 50-percent decreased risk of dementia. In addition, cholesterol is not only involved in the production of amyloid plaques in the brain, one of the hallmark features of the disorder, its metabolism requires the participation of the genes apoE E4 and CYP46. Both apoE E4 and the mutated version of CYP46 are implicated in the development of AD. These findings support several studies showing that the use of statins, which control cholesterol levels, lessens the chances of cognitive impairment.
Preventive dietary measures against AD call for limiting alcohol intake and increasing consumption of foods rich in antioxidants like vitamins E and C. To bring down high homocysteine levels in the blood, another risk factor for dementia, folic acid and vitamins B6 and B12 are recommended. One study also discovered that the three B vitamins appear to slow the progression of AD.
Part of a healthy lifestyle is regular exercise, which not only helps protect against brain damage caused by artherosclerosis, but also encourages the production of growth factors, chemicals that enhance the adaptability and survival rate of neurons.
Taking nonsteroidal antiinflammatory drugs (NSAIDs). Long-term use of ibuprofen, naproxen, and other NSAIDs may prevent or delay the onset of AD by controlling inflammation. Researchers found that widespread inflammation was common in the brains of deceased individuals who had AD. Furthermore, a recent study discovered that NSAIDs attach to beta-amyloid plaques, and may facilitate in their destruction and inhibit new plaque formations.
Pharmacological treatment
At present, there is no cure for AD, but medical research is making headway into two promising strategies for defeating the disease: disrupting the molecular cascade that leads to protein-plaque formation, and eliminating the plaque from the brain, which can be achieved in two ways. One is to prime the immune system against the beta-amyloid plaques by injecting an "active" vaccine containing part of the beta amyloid. The other is to inject antibodies directly. If all goes well, a marketable drug for stopping AD in its track will be available in three to 10 years. For now, patients afflicted with dementia rely primarily on cholinesterase inhibitors and memantine.
Cholinesterase inhibitors are a group of drugs used in the treatment of symptoms caused by dementia. They can temporarily improve or stabilize memory and other cognitive functions, reduce behavioral problems, and in the case of AD, slow down the progression of the disease for nine months or possibly longer. What they cannot do is stop or reverse AD, or prolong life. Cholinesterase inhibitors work by inhibiting the breakdown of neurotransmitters called acetylcholines, which are vital to memory and thinking skills. According to the US Alzheimer's Association, the drugs appear to modestly improve dementia symptoms in about half of the people who took them. Cholinesterase inhibitors include donepezil, rivastigmine, and galantamine, all of which have been out in the market for years. Tacrine, the first to be approved, is now rarely prescribed.
Memantine, prescribed for patients suffering from moderate to severe AD, functions differently from cholinesterase inhibitors. It regulates the activity of neurotransmitter glutamate, crucial to memory and learning. Glutamate, in turn, triggers cell receptors called N-methyl-D-aspartic acid (NMDA), the gatekeeper responsible for the entry of calcium into the cell. A healthy cell has just the right amount of calcium needed for information processing, storage, and retrieval. Too much calcium disables the cell, eventually leading to its demise, a phenomenon common in patients with AD. Memantine helps limit the inflow of calcium to nerve cells by partially blocking the NMDA receptors. It is the first to be approved in the US under the drug classification of uncompe-titive low-to moderate-affinity NMDA-receptor antagonist.
A study revealed that patients who were on a dual-drug treatment of memantine and donezepil exhibited better cognitive functions compared with those who were on donepezil alone. This suggests that combining memantine with a cholinesterase inhibitor may benefit the patient more than a single-drug treatment.
Vitamin-E supplements are often prescribed for AD, according to the Alzheimer's Assocation, to help augment the usually diminished levels of antioxidants in older people. Antioxidants protect cells from free radicals, oxygen molecules produced by normal cells that can paradoxically impair cell structures and genetic materials. The destructive process, called oxidative stress, is believed by some experts to contribute to the development of AD.
Drugs for agitation, a common symptom of dementia, run the gamut from antidepressants to anxiolytics to antipsy-chotics. Experts advise prescribing medication that focuses on specific symptoms to monitor the effects, and weighing risks and potential benefits each drug can offer to individual patients.
Antidepressants, such as citalopram, paro-xetine, fluoxetine, and sertraline, alleviate low mood and irritability. Anxiolytics, like lorazepam and oxazepam, help relieve anxiety, restlessness, and verbal aggression. Antipsychotic drugs control hallucinations, delusions, and hostile behavior. They include aripiprazole, clozapine, olanzapine, quetia-pine, risperidone, and ziprasidone. Also prescribed are anticonvulsants or mood stabi-lizers, like carbamazepine, and divalproex for hostility. M
The AD biochemical process
AD causes brain shrinkage and lesions primarily in the cortex and the hippocampus. Its trademark abnormalities are unusual clumps of protein known as beta amyloid, and masses of twisted protein filaments or neurofibrillary tangles.
The protein clumps or beta-amyloid plaques are found between nerve cells, along with bits of degenerating neurons. Scientists discovered three possible mechanisms that may explain how aggregates of beta amyloid contribute to the development of AD.
In one process, the plaques activate microglia-the brain's clean-up crew against potentially harmful substances-to secrete powerful neurotoxins called peroxynitrite, which in turn may assist in the disintegration of nerve cells in AD.
In another event, beta-amyloid buildup causes a protein called p35 to divide into two proteins, one of which influences the tau proteins to alter and twist into neurofibrillary tangles, a hallmark feature of AD.
The third-though not necessarily the last-in a series of phenomena that culminate to dementia, the beta amyloid triggers cell-death enzymes called caspases, which also corrupt the tau, leading to the formation of protein tangles.
Neurofibrillary tangles resulting from misfolding tau form inside neurons. Tau normalling helps in the functioning of microtubules, which deliver substances throughout the nerve cell and provide structural support. In AD, the taus pair up and twist into helix-shaped filaments that accumlate into tangles. The microtubules malfunction and die, causing cell collapse and communication breakdown between neurons. M
Depression among the elderly
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The most common psychiatric disorder among older people, depression is often undiagnosed or misdiagnosed. A Western study revealed that more than 50 percent of those aged 65 and above believe it is normal to get depressed with increasing age. In the Philippines, a stigma is attached to the disorder, particularly if it is experienced by the elderly. "The elderly will not say 'I feel hopeless, helpless, worthless.' I think it's a social and cultural thing that when you're old you shouldn't be saying these things," says Dr. Constatine Della, clinical associate professor at the University of the Philippines College of Medicine. Perhaps because of this, they tend to manifest depression through somatic symptoms, such as back pains, insomnia, headaches, and chest pains. "They go to the GP, who would give temporary relief, analgesic or something to put them to sleep, but it doesn't address the root of the problem," he says. "We, at PGH (Philippine General Hospital), have been advocating for the primary care physicians to be trained in identifying depression at their level, because it can be misdiagnosed." To compound the problem, depression is often obscured by a number of medical problems prevalent in old age, such as arthritis and cancer.
Whether it's a result of an illness or otherwise, depression is a serious problem that independently increases the risk of developing cardiac disease and the risk of death from illnesses. In old patients who had myocardial infarction, the development of major depression is associated with a fivefold heightened risk of death over the next six months. The ability to rehabilitate and everyday functioning are also seriously compromised. Left untreated, depression can result in excessive use of medication or suicide.
Late-onset depression, which begins later than age 60, differs from early-onset depression in a few significant points. The former exhibits a relatively high risk of recurrence that also lasts longer. Late-onset depression tends to be more chronic; that is, the cycles of remission-and-recurrence persist over extended periods. Some studies show greater apathy among depressed elderly, compared with younger adults. Cognitive impairment, such as declining memory, may also be evident but not as a function of dementia.
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The risk factors for depression among the elderly include chronic illness such as cancer, arthritis, hypothyroidism, hypertension, and diabetes; deficiency in nutrients like vitamin B12 and folic acid; previous depression; family history of depression; isolation; disability or change in body image; fear of death; widowhood; substance abuse; and use of depression-triggering medications, like beta-blockers, anticancer drugs, steroids, and sedatives. Stroke poses a high risk factor, with about one-fourth of the patients developing depression.
The Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) lists nine major symptoms of depression: loss of interest, sadness or depressed mood, significant weight change, sleep disturbance (insomnia or oversleeping), restlessness or slowing down, fatigue, feelings of worthlessness or guilt, trouble concentrating and making decisions, and suicidal thoughts or attempts. Major depression is diagnosed when the first two symptoms are present, and five or more of the symptoms persist for a minimum of two weeks. Minor depression is considered when only two to four symptoms are present. To measure depression in the elderly, physicians commonly rely on the geriatric-depression scale (GDS), which focuses on psychological symptoms alone.
Treatment for depression usually entails the use of antidepressants to help correct the chemical imbalance in the brain characterized by low levels of norepinephrine, serotonin, or dopamine. In people over 70 years old, selective serotonin reuptake inhibitors (SSRIs) are found to be the most effective way of preventing recurrence, according to a study. Compared with tricyclic antidepressants (TCAs), SSRIs appear to have fewer anticholinergic and cardiovascular symptoms. Common side effects of SSRIs include sexual dysfunction, nausea, vomiting, and other gastrointestinal problems. While TCAs are known to be an effective treatment for the elderly, they can cause dry mouth, urinary retention, cognitive disturbances such as confusion and impaired memory, and arrythmias, as well as exacerbating preexisting cardiac problems.
An equally valuable intervention method, psychotherapy can help patients cope with various triggers of depression. Effective techniques include cognitive-behavioral therapy, interpersonal psychotherapy, problem-solving therapy, brief dynamic psychotherapy, and reminiscence therapy, where patients reflect on their negative and positive life experiences. Some studies show that a combination of psychotherapy with pharmacologic intervention provides a more effective treatment than medication alone. M Sunly Coo
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