Alzheimer’s disease

What is Alzheimer’s disease?

Alzheimer’s disease is a neurodegenerative disease characterized by progressive neuronal loss and the accumulation of senile plaques and neurofibrillary tangles in brain tissue.

• The main component of senile plaques is beta-amyloid peptide. Unlike normal beta-amyloid peptide, the one that accumulates in plaques has an altered structure (beta-folded sheet), which gives it a marked tendency to aggregate and form fibers.
• Neurofibrillary tangles are located inside neurons and their main component is tau protein. Normal tau protein is part of the neuronal cytoskeleton. Pathological tau protein is abnormally phosphorylated and also aggregates in the form of fibrils.

The distribution of these lesions follows a characteristic sequence that explains the symptoms observed in the different stages of the disease. Thus, in the early stages,lesions are concentrated in the temporal lobes, responsible for fixation memory. As the disease progresses, the lesions spread to parietal and frontal associative areas.

What is the frequency of Alzheimer’s disease?

Alzheimer’s disease is the most common cause of dementia in our environment, where it represents 50-60% of all cases of dementia. The frequency of this disease is closely related to age. Most cases begin after the age of 65 years. However, there is a subgroup of patients with an earlier onset (presenile). A slight preference for the female sex has been observed.

What are the main causes of Alzheimer’s disease?

Most cases of Alzheimer’s disease appear in patients over 65 years of age without a determined cause (sporadic forms). Although the etiology in these cases is uncertain, we know that there are a number of risk factors that increase the probability of developing the disease. These include certain variants of apolipoprotein E (apoE4), low educational level, vascular risk factors (e.g. arterial hypertension, diabetes mellitus), head injuries and possibly some chronic infections (e.g. herpes group virus).

Less than 5% of cases have an autosomal dominant genetic origin. Genetic cases depend on mutations in the genes for presenilins 1 and 2 and amyloid precursor protein (APP).

What are the symptoms of Alzheimer’s disease?

The initial symptom usually consists of a progressive difficulty in remembering recent events. As the disease progresses, other higher functions are affected, including language (aphasias), execution of complex motor acts (apraxias), recognition of persons or objects (agnosias) and initiative, reasoning and abstraction abilities and other frontal or executive functions. Neuropsychiatric symptoms such as anxiety, depressed mood, delusions and hallucinations are also frequent.

How is Alzheimer’s disease diagnosed?

The diagnosis of Alzheimer’s disease is based on the recognition of the characteristic clinical picture and the exclusion of a number of processes that may produce similar symptoms. This requires a neurological assessment, blood tests and a brain imaging study (CT or MRI). In some cases it is necessary to perform other studies, including genetic analysis, cerebrospinal fluid analysis, electroencephalography or functional studies (PET, SPECT). With all these data a probability diagnosis is reached: probable Alzheimer’s disease. Definitive diagnosis would require analysis of brain tissue, but at present the risks of the procedure (brain biopsy) versus the benefits obtained mean that it is not indicated except in exceptional circumstances.

What is the treatment of dementia?

At present we do not have a curative treatment or one capable of blocking the progression of the disease, but we do have a number of symptomatic treatments.

• Non-pharmacological measures are essential. A familiar and protective environment should be organized for symptom control. Large calendars and clocks should be available so that the patient can easily update this information. During the day, patients should engage in physical and mental activities, which can improve their functional capacity, as well as nighttime sleep. The performance of these activities can be facilitated by attendance at day centers. The diet should be varied, low in salt, fats and sugars and rich in fruits and vegetables. Weight should be monitored periodically to correct deviations due to excess or deficiency. During the night it may be useful to keep a dim light.
• In terms of pharmacological treatments, the main drugs available include acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine. The former produce an increase in brain acetylcholine levels, a neurotransmitter involved in memory and found to be decreased in Alzheimer’s disease. These drugs reduce the rate of deterioration of higher functions transiently and can improve behavioral disturbances, especially apathy. They are indicated in mild to moderate stages of the disease. Memantine acts at another level, on glutamate receptors, and its current indications are limited to moderate to advanced stages. Apart from these specific treatments, symptomatic treatments such as antidepressants and sedative drugs are often necessary. The need for these medications varies at different stages of the disease, so their indications and dosages should be reviewed periodically.

How can I access research studies on Alzheimer’s disease?

There is currently intense research activity in the field of Alzheimer’s disease. In the coming years we will certainly see important advances, both in terms of treatment and in relation to the development of early diagnosis techniques and preventive measures. For example, several research groups are developing vaccines aimed at eliminating beta-amyloid peptide deposits.

Information about clinical trials and other research studies can be obtained through various websites(www.clinicaltrials.goc, https://medlineplus.gov/spanish) and scientific publications(https://www.ncbi.nlm.nih.gov/pubmed).

AUTHOR AND DATE OF ISSUE

DR. ADOLFO JIMÉNEZ HUETE

19/05/2020