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| Alzheimer’s disease: A neurodegenerative menace of elderly | | |
Dr. Wahied Khawar Balwan
Alzheimer’s Disease (AD) is the most common cause of dementia. This is an incurable, neurodegenerative and terminal disease.
INTRODUCTION
Dementia is a clinical manifestation in which decline in mental abilities and memory (cognitive functions) takes place in patients. The affected individual is not able to carry out his day-to-day activities. Older people with dementia are present worldwide. WHO predicts that around 71% of 81.1 m dementia cases will be in the developing world by 2040! There are no preventive or curative measures for most dementia cases. The most common cause of dementia is Alzheimer’s Disease or AD (around 60% cases). It is a progressive neurodegenerative disorder. The cases are confirmed by US National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association Criteria (NINCDS- ADRDA).
ETIOLOGY
Alzheimer’s Disease (AD) has a multi-factorial etiology. Various factors may increase the risk of dementia, viz. diet and lifestyle, mid-life history of disorders like hypertension, type 2 diabetes etc. and genetic predisposition. The behavioural and psychological symptoms are apathy, depression, sleep alterations, anxiety etc. In India, patients suffering from AD have delusions, hallucinations, anxieties, phobias and caregiver distress. These are similar to those reported from developed countries. Early life exposure to deleterious conditions like poverty, infectious diseases, malnutrition, pre-natal stress may influence ageing process. Early life negative events and physical attributes including brain development, body growth, socioeconomic conditions, head injury contributes as risk factors of AD. Intellectually stimulating and socially engaging physical activities lowers the risk of AD. Also diet rich in fruits, vegetables and fibres significantly reduce development of AD.
PATHOLOGY
This incurable, degenerative and terminal disease was first described by German physicist, Alois Alzheimer in 1906 and was named after him. Both amyloid plaques and neurofibrillary tangles are visible in brains of AD patients on autopsy.
AD has been identified as a protein mis-folding disease, caused by accumulation of abnormally folded ‘AB’ (amyloid B) protein and ‘tau’ proteins in the brain. Majority of AD cases are sporadic. A few of the familial forms follow autosomal dominant inheritance, which usually have an onset before 65 yr. Most of the inherited AD are attributed to mutations in one of the three genes: Amyloid Precurssor Protein (APP), Presenilin 1 (PS 1) and Presenilin 2 (PS2). Amyloid plaques are formed between nerve cells in the brain. AB is formed after sequential cleavage of APP, a transmembrane glycoprotein of unknown function. Beta amyloid form clumps, that deposit outside neurons.
APP can be cleaved by A,B and Y secretase to from AB proteins of various lengths. A number of isoforms are generated varying in length viz. AB-40 and AB-42. Shorter forms e.g. AB-40 is more common and is produced by cleavage in trans-golgi network. AB- 42, produced in endoplasmic reticulum is more fibrillogenic and is associated with plaques. Mutations in PS1 and PS2 alter the Y secretase activity, such that AB-42 is produced. Beta amyloid peptide activates the surrounding microglia and astrocytes producing inflammatory mediators e.g. components of complement pathway, acute phase proteins, interleukin-6 etc. This may help in the formation of AB. The other protein implicated in AD, tau protein, forms prion like misfolded oligomers. Neurofibrillary tangles are insoluble twisted fibres found inside the neurones. The tangles primarily consist of tau, which forms part of microtubule, which helps transporting nutrients and other important substances from one part of neurons to the other. In AD, tau protein is abnormal and microtubule structure collapse. Nonetheless most of AD cases do not exhibit autosomal dominant inheritance and are sporadic, genetic differences may act as risk factors. One of the risk factors is E4 allele of apolipoprotein E. This allele has been widely studied and is a well-established risk factor for AD. Many studies have been conducted to find an association of interleukin6–174G/C polymorphism and AD with varying results.3 There are other genes which may act as risk factors or have protective effects on AD.
DIAGNOSIS AND TREATMENT
AD is diagnosed clinically from patient history, clinical observations, presence of characteristic neurological and psychological features and absence of alternative conditions. Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI) and Single Photon Emission Computed Tomography (SPECT) or Position Emission Tomography (PET) can be used to help exclude other cerebral pathology. Currently used treatments have symptomatic benefits. Developing countries have traditional herbal medicinal practices that are good anti-dementia therapies. Several species of medicinal plants e.g. blueberry, cannabis, clubmoss, curcumin, garlic, ginseng, pomegranate etc. have activities relevant to dementia. Modern treatments of AD are pharmaceutical, psychosocial and caregiving. Mementine (NMDA receptor antagonist) is the drug of choice. Acetylcholine esterase inhibitors are also used. Antipsychotic drugs are also used for reducing aggression and psychosis. Psychosocial therapies include behavioural, emotional, cognitive and stimulatory. Since AD has no cure, caregiving must be carefully managed over the course of the disease. Clinical research is focused on treating the pathology of the disease. Immunotherapy and vaccination for the amyloid protein is one of the treatment modalities under investigation.
SCENARIO IN INDIA
In India, more than 4m people are estimated to be suffering from AD and other forms of dementia, giving the country the third highest case-load in the world, after china and the US. AD in India is a hidden problem. Only a fraction of patients are diagnosed and treated. According to India Ageing Report, 2017, the elderly population, which is growing at a fast rate of 3%, may increase the AD cases.
According to a study, social stigma surrounding AD and dementia is impeding early diagnosis, care and research. AD modifies survival and increases the risk of death. Understanding the burden and cost of AD is crucial for future healthcare and socioeconomic policy. Teaching of coping strategies to the caregivers has improved their psychological health. National Policies to increase awareness, specialized training for health professionals, authorities, research and a proper counseling of caregivers etc. may help the growing number of AD and other dementia patients in the long run.
CONCLUSION
Alzheimer’s disease (AD), being an incurable, degenerative disease requires special care of patients. Various factors like lifestyle, diet, genetic predisposition are thought to cause the disease. Palliative treatment, social awareness and early diagnosis are important. Trained care-giving is an essential part of the disease.
‘Any error in this manuscript is silent testimony of the fact that it was a human effort’ |
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