Alzheimer's - Treatments for Behavior Disorders and Alternative Therapies

Behavioral disorders in a patient with Alzheimer's disease

Disorders of behavior, mood and psychotic symptoms, which often accompany the individual suffering from Alzheimer's disease, are not only caused by cerebral degeneration but also by the way in which the patient adapts to his progressive incapacity.

In general, behavioral disorders begin with small changes and then progress to cause serious social disorders. This situation can seriously compromise the care and health of the patient and includes states of agitation, aggression, restlessness, insomnia and wandering aimlessly. Furthermore, the patient suffering from Alzheimer's disease is at greater risk of hallucinations and delirium. The behavioral disorders to which an Alzheimer's patient is most affected are anxiety, apathy and depression.

Antipsychotic medications are useful for symptoms such as hallucinations and delirium. In particular, normally, these can be distinguished in old generation antipsychotics, the use of which must be limited to conditions of particular emergency and in any case for a limited period of time, and the so-called new-generation or atypical ones. The latter are used to treat behavioral disorders of dementias and have fewer side effects, such as sedation or motor slowing, compared to older drugs.

Among the most commonly used new generation drugs are Abilify, Clorazil, Zyprexa, Seroquel and Risperdal.

It is important to emphasize that patients suffering from Alzheimer's disease are at greater risk of developing adverse effects, including the metabolic syndrome, a set of metabolic risk factors that increase the possibility of developing heart disease, stroke and diabetes.

The onset of neuroleptic malignant syndrome, characterized by hyperthermia, muscle rigidity and altered state of consciousness, has also been reported.

One of the most recent antipsychotic drugs, approved by the European commission in 2010, Sycrest (in Europe) or Saphris (in the USA), has shown promising results in the treatment of neuropsychiatric symptoms that may arise in Alzheimer's patients. The promising results obtained with this drug are probably due to the fact that it causes minimal adverse cardiovascular and anticholinergic effects, as well as a minimal weight gain (weight gain).

In patients with Alzheimer's disease, depression is also very common, since the affected individual is faced with various emotional reactions that include fear, terror and killing, triggered by the cognitive decline that the disease progressively leads to with loss of independence . The signs and symptoms of depression in Alzheimer's patients are very difficult to recognize, because some characters are also typical of Alzheimer's disease, such as anorexia, insomnia, weight loss, and anhedonia.

If these symptoms characterized by a mood disorder are present and compromise the quality of life, first of all a non-pharmacological approach should be implemented, subsequently supported by antidepressant drugs. Generally these drugs are indicated in the treatment of depression and can often be useful to distinguish the "classic" depression that responds to treatment, from the prelude to the subsequent evolution in dementia, whose response to the drug is rather dubious.

Among the antidepressant drugs used are:

  • Selective serotonin re-uptake inhibitors (SSRIs): generally considered the first choice, thanks to the low profile of adverse effects compared to other classes of antidepressants. SSRIs include Celexa, Lexapro, Zoloft, Prozac, Paroxetine.

    The side effects of SSRIs are generally gastro-intestinal in nature and can be managed starting with a low dosage, which can then be increased or decreased gradually.

  • Another antidepressant drug with tetracyclic structure, Remeron, is a presynaptic α2-antagonist, which increases noradrenergic and serotonergic transmission in the central nervous system. Remeron was useful in patients with Alzheimer's disease who presented with depression associated with insomnia, poor appetite and weight loss. It should be considered, however, that this drug could prove to be a wrong choice in the case of overweight patients or those at risk of metabolic syndrome who have diabetes mellitus.
  • Serotonin and noradrenaline re-uptake inhibitors (SNRIs). Among these we find Effexor, Pristiq, Cymbalta. In particular, these drugs can be useful in patients suffering from Alzheimer's disease and already being treated with pain medications, particularly arthritis.

However, serotonin and noradrenaline re-uptake inhibitors should be avoided in individuals with hypertension; they can also aggravate insomnia.

If the subject suffering from Alzheimer's disease shows symptoms of mania or mood swings, mood-stabilizing drugs are needed. However, many precautions must be taken in the use of this class of drugs, due to the potential side effects. They remember in this category of drugs: Depakote which affects patients at risk of weight gain, hyperglycemia and hyperlipidemia. However, this drug is also associated with a worsening of cognitive functions.

Another mood-stabilizing drug is Tegretol which has been shown to reduce aggression. However its use requires the monitoring of vital and blood functions. It is also a difficult drug to dose because it alters the metabolism of many other drugs, as well as the metabolism of the drug itself.

In the event that a person suffering from Alzheimer's disease experiences sleep disorders, a behavioral intervention is preferable to drug therapy. In fact, those who care for a patient suffering from Alzheimer's disease must educate the patient by encouraging useful behaviors to establish a good sleep-wake rhythm. Some medications can be useful for improving sleep. Among these, for example, melatonin is useful, present in many drugs over the counter (OTC, Over The Counter). Another famraco used is Trittico, an antidepressant that is highly sedative and can be used safely at low doses to improve sleep quality.

Benzodiazepines, on the other hand, are not recommended in individuals suffering from Alzheimer's disease, due to adverse effects, including a worsening of memory functions, progressive loss of muscle coordination (ataxia), disinhibition and drowsiness.

Alternative and Complementary Therapies

As Alzheimer's disease is a progressive and multifactorial neurodegenerative disease, alternative and complementary therapeutic approaches are also sought. These new therapies are generally not subjected to the typical scientific investigations, which provide for FDA approval; however many of these therapies are recommended by doctors, but also by other specialists, especially with regard to cases of elderly people who, together with Alzheimer's disease, also manifest the classic cardiovascular diseases and different forms of arthritis.

For example, epidemiological studies have shown that aspirin and other non-steroidal anti-inflammatory drugs may be able to "protect" from Alzheimer's and other forms of dementia. Studies conducted on animals, in fact, have shown that using non-steroidal anti-inflammatory drugs a β-amyloid suppression was observed, which as previously introduced is present in the form of plaques in the brain affected by Alzheimer's disease. However, randomized studies conducted in groups of individuals, using non-steroidal anti-inflammatory drugs, did not give satisfactory results. Furthermore, it should be remembered that both aspirin and other non-steroidal anti-inflammatory drugs involve cardiovascular risk, gastrointestinal haemorrhage and kidney problems. Therefore, these drugs should not be indicated exclusively for the treatment of Alzheimer's disease, but should be used for concomitant use, for example as a low-dose antithrombotic, only on medical indication.

It has also been suggested by recent studies that, in Alzheimer's disease, oxidative stress would play a key role, although it has not yet been clarified whether this is a primary pathogenic event or whether it is a secondary event in the activation of pathogenic mechanisms . In patients with mild cognitive impairment, increased levels of oxidative stress have been found. This indicates that it is probably a phenomenon involved in a precocious and causal manner in the neurodegenerative process. Following increased intake or elevated antioxidant plasma levels, some observational studies have found a reduced risk of dementia. Therefore the use of substances with antioxidant activity could be a rational approach for the prevention and treatment of Alzheimer's disease.

Among these substances, vitamins A, C and E, the well-known Coenzyme Q10, idebenone, acetylcysteine, selegiline, ginkgo biloba and selenium deserve attention. However, the data currently available on their effectiveness are negative or inconclusive; an explanation to these results could reside, at least in part, in problems of a methodological type, such as for example an unsuitable duration of the treatment, the use of non-optimal dosages, an incorrect therapeutic window and others. In fact, the experimental results indicate that oxidative stress is a very early event in the onset of the disease. This suggests that perhaps antioxidants act primarily at the level of primary prevention.

Particular attention deserves vitamin E. It exists in the form of eight isoforms and, currently, the studies conducted have used only one of these isoforms, α-tocopherol. Growing evidence suggests that other vitamin E isoforms seem to play a protective role against cognitive decline and Alzheimer's disease. Further studies will be needed to clarify the role of antioxidants, also in light of the fact that these products, being sold as over-the-counter products, have an increasingly widespread use and are also taken without medical supervision. It is important to point out that some recent meta-analysis studies have shown an increase in mortality associated with the use of antioxidants, such as vitamin E, beta carotene and vitamin A. At high doses, vitamin E appears to aggravate vitamin K deficiency in disorders of coagulation thus increasing the mortality of elderly people.

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