Hopes and prospects on prevention, treatment and management of dementia
Detailed Programme, abstracts and presentations
PL2.1. Treating Alzheimer’s disease
Alzheimer’s disease (AD) is characterised by a gradual loss of nerve cells and nerve cell connections. Major underlying pathological mechanisms include the aberrant processing and subsequent accumulation of two nerve cell proteins, beta amyloid and tau. The total duration of AD is 20 to 30 years and can be divided in 3 major phases. During the first phase, the process does not cause any symptoms. This is followed by a stage of increasing forgetfulness which has no significant impact on the management of day-to-day tasks. In the third phase impairments of memory and other cognitive functions become so severe that usual activities of daily living cannot be maintained and affected individuals become increasingly dependent on others. This condition indicates widespread brain damage and is termed “dementia”.
Current medications for the treatment of AD correct alterations in chemical messenger systems which arise as a consequence of nerve cell dysfunction. These drugs have no demonstrable effect on the demise of cells. They can be administered only after the onset of dementia, and their effects are limited to delaying the progression of symptoms for several months.
Treatments are in development which aim at slowing down or even arresting the loss of nerve cells. Major therapeutic strategies address abnormal protein production, aggregation, degradation and clearance. If proven efficacious, safe and tolerable these treatments could be administered long-term at the stage of minor symptoms in order to preserve functional ability and quality of life and to delay the onset of dementia.
While such novel treatments may reduce the incidence of disability and dependence, they will prolong the time patients and their families struggle with cognitive impairment. Therefore the evolution of more powerful drugs must be complemented by the development of non-pharmacological interventions and community services which help affected individuals cope across the clinical course of AD.
PL2.2. The genetics in Alzheimer’s disease
Alzheimer disease (AD) is the most common cause of dementia. The prevalence of AD increases with age: approximately 10% of persons over the age of 70 have significant memory loss and more than half of these individuals have AD. Alzheimer’s disease is characteriszed by dementia that typically begins with subtle and poorly recognised failure of memory and slowly becomes more severe. Other common findings include confusion, poor judgment, language disturbance, agitation, withdrawal, and hallucinations.
Neuropathologic findings of β-amyloid plaques and intraneuronal neurofibrillary tangles remain the gold standard for diagnosis. A buildup of toxic amyloid beta peptide and amyloid plaques lead to the death of nerve cells and the progressive signs and symptoms of this disorder. The main challenge that we are now facing is identifying people who are at high risk for developing AD so they can benefit from new interventions and treatments as soon as possible.
Testing of asymptomatic adults at risk for early-onset familial Alzheimer disease (FAD) caused by mutations in the PSEN1, PSEN2, or APP gene is available clinically. When any of these genes is altered, large amounts of a toxic protein fragment called amyloid beta peptide are produced in the brain. It should be remembered that testing of asymptomatic at-risk individuals with nonspecific or equivocal symptoms is predictive testing, not diagnostic testing.
Preliminary results have shown that while relatively few family members choose such testing, they usually cope well with the results, although they can affect personal relationships and emotional well-being. However, significant depression following such testing has also been reported.
Most cases of AD are the late-onset form, which develops after the age of 60. The causes of late-onset, sporadic AD are not yet completely understood, but they likely include a combination of genetic, environmental, and lifestyle factors that influence a person's risk for developing the disease. The single-gene mutations directly responsible for early-onset Alzheimer's disease do not seem to be involved in late-onset Alzheimer's. Researchers have not found a specific gene that causes the late-onset form of the disease. However, one genetic risk factor does appear to increase a person's risk of developing the disease. This increased risk is related to the apolipoprotein E (APOE) gene found on chromosome 19.
APOE comes in several different forms, or alleles. Three forms - APOE ε2, APOE ε3, and APOE ε4 - occur most frequently. Having one or two copies of the E4 allele increases a person's risk of getting Alzheimer’s disease. That is, having the E4 allele is a risk factor for Alzheimer’s disease. The public policy statement supports the use of apoE testing for diagnostic purposes only in conjunction with other tests during medical evaluations of patients who show Alzheimer’s disease symptoms. It recommends not using apoE testing as a patient screening (predictive) method.
Several other potential genes under investigation: SORL1, A2M, TOMM40, CLU, APOJ, CR1 and PICALM, are implicated in two genome-wide association studies (GWAS). There is some emerging evidence that epigenetic mechanisms also contribute to AD. Epigenetic changes, whether protective, benign, or harmful, may help explain, for example, why one family member develops the disease and another does not. The decision to participate in genetic testing is a personal one. Genetic counseling for people with non-familial AD and their family members must be empiric and relatively nonspecific. Predictive screening in otherwise healthy people will be useful when effective ways to treat or prevent AD are available.
DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.
PL2.3. Psycho-social interventions in dementia
Psychosocial interventions aim to improve the quality of life of both the person with dementia and their caregiving relatives. They support persons with dementia and their relatives in dealing with the diagnosis and the disease. Recent research findings indicate that they have the potential to do so.
Effective psychosocial interventions in community care are occupational therapy, psycho-education, cognitive reframing and case management. They improved caregivers’ sense of competence and reduced patients’ and caregivers’ depression. In long term care settings reminiscence, multi-component interventions and cognitive training reduced behavioral problems. Multi-component interventions reduced patient institutionalization.
There is no intervention that fits everyone. Interventions that are multi-component, aim at the needs of both the person with dementia and the relative and are intensive are more often effective. Psychosocial interventions are as effective or even more effective than pharmacological interventions.
However, not all interventions have positive effects, indicating that not each intervention that is meant to support persons with dementia and their relatives is supportive. Although, psychosocial care is usually provided with the best of intentions, it is often not appreciated as such. Social support is often ineffective because of the emotional costs of receiving support: dependency threatens self-esteem. Future psychosocial intervention should consider more the capacities of the person with dementia and their desire to be a participating citizen. Being able to give something back is largely ignored as a basic social need. Acknowledging the norm of reciprocity for all citizens can prevent or mitigate the loss of autonomy and dignity of people who are dependent on care. This might improve social inclusion and the quality of life.
Last Updated: mercredi 23 novembre 2011