Early Detection Alzheimer’s in Elderly Patients

Detecting Dementia

Making the diagnosis of dementia is reasonably straightforward in the moderate and severe stages, but it can be problematic to distinguish the early stages of Alzheimer’s from “normal” ageing in elderly patients, although recent development has helped to clarify which neuropsychological tests discriminate most effectively. Most people who present with concerns about memory problems do not in fact have dementia, and it is also important to note that in specialist clinical practice professionals see an atypical group of patients. O’Connor (1994) found that only 3% of people identified in a community survey as having mild dementia had been referred to specialist services, along with 18% of those with moderate dementia and 33% of those with severe dementia.

Early Detection

Interest in the early detection of Alzheimer’s has increased with the recent licensing of anti-cholinesterase inhibiting medication as a treatment for the cognitive impairment of early-stage Alzheimer’s. This detection on early-stage of the disease is increasingly undertaken in the context of multidisciplinary memory clinics, where neuropsychological assessment plays a critical role in establishing a diagnosis. Early detection of DAT offers the possibility of introducing psychosocial and pharmacological interventions at an early stage. It has been demonstrated that memory clinics can provide an effective focus for early intervention and for the development of integrated psychosocial approaches. Early detection of Alzheimer’s remains a challenge, however, and there are a number of barriers to early detection. People with dementia, and their families, may interpret certain memory impairment of the patients as part of normal ageing process or deny that there have been any changes, and rates of detection by general medical practitioners are low.

Distinguishing Dementia from “Normal” Ageing

The boundaries between dementia and normal forgetfulness still appear somewhat fluid, and it remains unclear how the difference between dementia and normal ageing should be conceptualized. Although many older people and their families expect to observe a decline in memory functioning, there is a great deal of variation in the general population as regards the kinds of memory changes seen as part of “normal” ageing, and the issue is compounded by cohort effects. A broad overview suggests that, although memory functioning becomes less efficient from about 67 years onwards there is no general decline in memory ability and no uniform decline across the range of different memory tasks. Memory functioning is relatively more affected in the very old, so that diagnostic criteria do not allow for a dementia diagnosis made after the age of 90. The following general observations can be made with regard to memory changes in healthy older people:

• Working memory may be affected.
• Episodic memory is affected to a much greater degree than semantic or procedural memory.
• Immediate recall is affected more than delayed recall, while recognition memory is unaffected.
• Retrieval is slower and less efficient, with more rapid and extensive forgetting.
• Prospective memory remains as good as that of younger people if external aids and reminders can be used, but is poorer if no such aids are available.
• Autobiographical memory does not show the stereotypical discrepancy between vivid memories of the distant past and hazy memories of more recent events; instead, memories across the lifespan show loss of detail and become vaguer.
• Alterations in memory functioning can be offset by intelligence, expertise and use of compensatory strategies, enabling the person to cope well despite any changes.

What is “Normal” Memory Loss?

• Forgetting people’s names occasionally;
• sometimes not being able to find the right word;
• taking longer to learn new things;
• sometimes forgetting where one has put things, like keys, for example;
• sometimes forgetting what one has come into a room to do.

What are the Symptoms of More Serious Memory Loss?

A more serious memory problem is one that affect’s a person’s ability to carry out everyday life activities such as driving a car, shopping or managing money. Some of the signs are:

• asking the same questions over and over;
• getting lost in familiar places;
• not being able to follow directions;
• confusion over time, people and places;
• forgetting to eat right and regularly;
• not bathing;
• poor judgment about safety;
• driving problems.

Medicines That Cause Forgetfulness

Forgetfulness is common among drug and alcohol abusers, but certain medicines also list forgetfulness as one of their side effects. Due to the age-related medical conditions, elderly people are more affected by the negative side effects, caused by medications. Approximately 163,000 people in the United States are estimated to experience serious cognitive impairment either caused or worsened by drugs.

For example, a beta-blocker medication, such as Inderal, generic name propranolol, or Lopressor, generic name metoprolol, may cause short-term memory problems. Similar results have been reported in patients who use such medications which contain the active ingredient methyldopa. Additionally, many antidepressants cause memory-related problems, especially in the beginning of the treatment. The same applies to anti-anxiety medicines like lorazepam and alprazolam or sleeping pills like triazolam. Benzodiazepines that are used to treat such disorders as anxiety, restless legs and social phobias seem to cause forgetfulness. Tranquilizers that are used to treat such conditions as Tourette syndrome and irritable bowel syndrome also seem to cause forgetfulness in some patients. Some drugs aimed at reducing high levels of cholesterol have also been criticized for such side effects. Even over-the-counter medicines, such as the antihistamine diphenhydramine, have been linked to forgetfulness.

The Boundaries between Dementia and “Normal” Ageing

As a general rule, the lower the score on cognitive tests, the more likely it is that the person has dementia. However, Storandt & Hill (1989) found that scores of patients with very mild Alzheimer’s overlapped considerably with those of both normal older people and people with mild Alzheimer’s. Furthermore, even where people do show some degree of memory impairment, progression to dementia is not inevitable.

The area of uncertainty between “normal” ageing and dementia has attracted a number of attempts to define diagnostic categories. Among the diagnostic labels suggested are age-associated memory impairment (AAMI), mild cognitive impairment, benign senescent forgetfulness, and minimal or questionable dementia. These concepts remain controversial, and practice varies regarding their use. The category of AAMI, for example, would include large numbers of older people, and it is questionable whether changes that are essentially normative should be labeled in this way.

Which Tests Are Useful in Discriminating between Dementia and Normal Ageing?

The CERAD studies suggest that the best discriminator is performance on delayed recall tasks. A 10-word list presented in three learning trials and tested after a 5–8 min delay correctly classified 94% of controls and 86% of patients with mild dementia, using a cutting score of 2 SDs below the control group mean. Performance on naming tests was found to be useful as an adjunctive measure. If patients have impairment in delayed recall and problems in naming or verbal fluency, this is a very strong indicator for dementia. Other studies have also emphasized the value of delayed recall. Tierney et al. (1996) found that problems in delayed recall and attention were the best predictors of whether people with mild memory problems would go on to develop Alzheimer’s disease.

Sources and Additional Information:

The Book of Memory Disorders by Alan D. Baddeley

http://www.suite101.com/content/memory-loss-in-the-elderly-a57376

http://www.livestrong.com/article/161728-what-are-the-causes-of-sudden-forgetfulness-in-the-elderly/

http://www.wrongdiagnosis.com/sym/forgetfulness.htm

Children’s Alzheimer’s: Niemann-Pick Type C Disease

Twin 4-year-old girls Addison and Cassidy Hempel are similar to their contemporaries in many ways: They love nursery rhymes; "Humpty Dumpty" is the family favorite; they go to school and play house. But the identical siblings differ from other children in one major way.

The girls' world of childhood fantasy is haunted by a heartbreaking reality that they are fighting a disease that seeks to steal their memories. Like a pediatric version of Alzheimer's disease, Niemann-Pick Disease Type C (NPC), from which the girls suffer, causes patients to slowly lose their motor skills and then their minds. Rarely do children with NPC live past their teenage years. In fact, the National Niemann-Pick Disease Foundation says NPC always is fatal and the vast majority of children die before age 20 -- with many not making it to the age of 10.

Niemann-Pick Type C Disease as Children Alzheimer’s

While formally speaking, Alzheimer’s (AD) and Niemann-Pick Type C Disease (NPC) are absolutely different disorders, NPC is frequently referred as Children Alzheimer’s. In comparison with AD, which affects more than 5 million people just in USA, the NPC is much rarer. It affects currently less than a 100 people currently living in the United States, and about 500 cases have been diagnosed ever worldwide. NPC is described as a genetic degenerative neurological disorder that mostly strikes during childhood that stores fatty lipids in the brain, liver, spleen, and bone marrow because of the cells inability to metabolize cholesterol. Although uncommon, adult onset can take place with NPC. Outcome is also fatal with no cure.

Whether it is Niemann-Pick Type C Disease (NPC) or Alzheimer’s, they are extremely saddening to experience as a loved one. One affects mostly older adults and the other strikes predominantly in adolescents. Regardless, a main symptom in each disease is progressive Dementia along with similar pathological features that include the loss of intellectual function.

What is Niemann-Pick?

Although not widely known by the public and classified as rare by medical science, Niemann-Pick Disease (NPD) Type C has been the subject of worldwide medical research for many years because it is considered an important link in the battles against heart disease, Alzheimer’s, stroke & seizure disorders. Basically, an inherited biochemical deficiency results in the body’s inability to metabolize cholesterol properly. Consequently, cholesterol begins to accumulate in the liver, the spleen and the brain - a process which eventually results in serious neurological damage. The pathological effects of this disease were first noted around the turn of the century but, of course, its origins go back much further in time. In fact, a closely related variant of NPD-C (known as Type D) has been traced back to its originators in Nova Scotia in the mid- 1700’s. With the discovery last summer of the primary gene associated with NPD-C medical research has intensified worldwide, and at least one drug has been found which delays the onset of serious effects but it is not yet ready for clinical trials. Usually, the effects of Niemann-Pick Disease Type C (deterioration of motor skills, slurred speech, etc.) don’t appear until the early school years (although there is also a young adulthood onset type). Children seldom survive beyond their 15th birthday. In some cases, the prognosis is more difficult because of his early age, but serious effects could begin in as few as two years.

How it is Diagnosed?

Unfortunately there is no quick available test that will give you the answer. If foamy macrophages appear it is a strong possibility of a Lysosomal Storage Disease. The test can take up to 6-8 weeks to receive the results from the blood work and skin biopsy that is collected. When you are told that your child or children have a fatal disease, this time period turns into an eternity of worried thoughts.

Treatment

There is no treatment for NP-C, but supportive therapies are available. These include medications to control seizures, abnormal posturing of limbs and tremors. Physical, speech and occupational therapy are also used to help with daily functioning. A low cholesterol diet and cholesterol-lowering medications do not appear to influence the course of this disease, and studies have shown no affect on the neurological progression. Currently a drug called Zavesca (Miglustat) which is FDA approved for Gaucher’s Disease Type 1 (the most common Lysosomal Storage Disorder) is only available by mail through Curascript and is being used in NP-C patients off label.  Off label basically means that it is prescribed for a purpose outside the drug’s original scope of approval. It has shown to help buy more time but the drug is not currently FDA approved in United States for use with Niemann Pick Type C Disease. This drug costs typically $159,000 per child a year.

Side Effects of NPC

When brain cell function is blocked NP-C children lose coordination (Gelastic Cataplexy), stumble, fall (Ataxia) and eventually need to be in wheelchairs, sleep in a hospital bed and utilize other adaptive equipment.  As the disease worsens other devastating symptoms develop including loss of the ability to speak (Aphasia), swallow (Dysphagia), laugh, remember (dementia), trouble moving eyes (Vertical Gaze Palsy) and often seizures occur.  The health of children with NPC deteriorates until ultimately, the disease claims the child’s life.

Sources and Additional Information:
http://abcnews.go.com/GMA/OnCall/story?id=4760023&page=1

http://www.gabriellelaverde.com/index_files/NiemannPick.htm

http://www.bripardun.com/npc.html

http://www.npcfund.org/2010/05/childhood-alzheimers/

http://www.msnbc.msn.com/id/30247453/

Three common types of Alzheimer’s disease

There are three commonly known types of Alzheimer’s disease. They include:

Early-onset Alzheimer's

This is a rare form of Alzheimer's disease in which people are diagnosed with the disease before age 65. Less than 10% of all Alzheimer's disease patients have this type. Because they experience premature aging, people with Down syndrome are particularly at risk for a form of early onset Alzheimer's disease. Adults with Down syndrome are often in their mid- to late 40s or early 50s when symptoms first appear.

Younger people who develop Alzheimer's disease have more of the brain abnormalities that are associated with it. Early-onset Alzheimer's appears to be linked with a genetic defect on chromosome 14, to which late-onset Alzheimer's is not linked.

Mutations of three genes, namely presenilin 1, presenilin 2, and amyloid precursor protein, are associated with Early Onset Alzheimer’s disease. These genes in isolation do not cause Alzheimer’s, however, mutations of these genes, can cause the disease.

Changes in the brains of younger people affected by Alzheimer’s disease are microscopic, involving twisting of nerve cells “known as neurofibrillary tangles” and formation of structures called plaques by a sticky protein called beta amyloid. These plaques and tangles tend to damage healthy brain cells leading to shrinking and atrophy.

A condition called myoclonus which causes muscle twitching and spasms is much more common in people with early onset than those who develop the disease later in life. These will all combine to make it very difficult for someone in the younger age group to continue to work or even take part in normal family life.

Individuals with early-onset Alzheimer's disease will exhibit many of the same symptoms as those whose disease appears later in life. Memory loss, confusion, personality changes and difficulties performing simple tasks are all very common symptoms and as the disease progresses emotional and social withdrawal is the norm. Anyone who has this combination of symptoms should see a physician as soon as possible.

Alzheimer's diagnosis usually comes as a result of ruling out all other possibilities. The only way to biologically diagnose it is to examine brain tissue under a microscope, which is typically done only after death.

Late-onset Alzheimer's 

This is the most common type of the disease affecting about 90% of all those with Alzheimer’s. It affects people over the age of 65 with around 50% of all people over the age of 85 suffering from it. And the likelihood of developing late-onset Alzheimer’s doubles every five years after the age of 65. Late-onset Alzheimer's disease may not be hereditary.

It is also known as “sporadic Alzheimer’s” because it can affect any elderly person with no other common link other than the fact that they are all over 65.

Late onset Alzheimer’s causes memory loss, confusion and difficulties in carrying out even the simplest tasks. Eventually a person will need constant care as they will be unable to look after themselves.

On average people live roughly eight to ten years after diagnosis. Sometimes with sporadic Alzheimer’s, because it affects people so late in life, another disease associated with old age could also be the cause of death.

There is no cure and the jury is still out as to why some people get it and others don’t. It is indiscriminate of race, color, creed and lifestyle. In fact the only thing sufferers have in common appears to be old age.

Unfortunately finding genes for incredibly complex conditions like sporadic Alzheimer’s is a complicated business as there appears to be no link between who gets it and who doesn’t. So far researchers haven’t come across one single common factor to determine the eventual development of late-onset Alzheimer’s. What they have done, however, is identify a gene which may be a risk factor. Apolipoprotein E (ApoE) is interesting in that it has both a negative and positive side in the development of Alzheimer’s. The e4 type of the gene is found to carry a higher risk of Alzheimer’s while the e2 type is believed to offer protection against it. Having this gene doesn’t necessarily mean that a person will get Alzheimer’s – what it does mean is that it may increase their risk. Environmental factors, lifestyle and toxins can all play a part in weakening genes and making a person more susceptible to an illness.

Sporadic Alzheimer’s is a very difficult and complex disease for researchers because there is no real rhyme or reason to it. Until they can come up with an identifying factor other than age, there will be no cure.

Familial Alzheimer's disease (FAD)

This is a form of Alzheimer's disease that is known to be entirely inherited. In affected families, members of at least two generations have had Alzheimer's disease. FAD is extremely rare, accounting for less than 1% of all cases of Alzheimer's disease. It has a much earlier onset (often in the 40s) and can be clearly seen to run in families. In some extremely rare cases people in their 30s have been known to develop it.

Histologically, familial AD is practically indistinguishable from other forms of the disease. Deposits of amyloid can be seen in sections brain tissue (visible as an apple-green yellow birefringence under polarized light). This amyloid protein forms plaques and neurofibrillary tangles that progress through the memory centers of the brain. Very rarely the plaque may be unique, or uncharacteristic of AD; this can happen when there is a mutation in one of the genes that creates a functional, but malformed, protein instead of the ineffective gene products that usually result from mutations.

This type is genetically inherited due to a fault on chromosomes 1, 14 or 21. When this happens roughly 50% of the offspring of these sufferers will carry the genetic fault and all of them will go on to develop Alzheimer’s.

Mutations in three different genes -- the amyloid precursor protein (APP) gene and the presenilin 1 and 2 (PSEN1 and PSEN2) genes -- have been discovered in families with early-onset familial Alzheimer's disease. Taken together, these mutations only account for about 20-50% of familial Alzheimer's, indicating that other genes remain to be found in this disorder.

The APP gene encodes the beta-amyloid protein which accumulates abnormally in the brain in Alzheimer's disease. The protein products of the PSEN1 and PSEN2 genes interact with proteins are involved in signaling processes within and between cells.

Sources and Additional Information:

http://www.webmd.com/alzheimers/guide/alzheimers-types

http://www.omnimedicalsearch.com/conditions-diseases/alzheimers-disease-types.html

http://www.guide4living.com/alzheimers/types.htm

http://www.revolutionhealth.com/articles/types-of-alzheimers-disease/2341

http://alzheimers.about.com/lw/Health-Medicine/Conditions-and-diseases/Coping-With-Early-Onset-Alzheimers-Disease.htm

http://www.economicexpert.com/a/Familial:Alzheimer:disease.html