What is Alzheimer’s disease?
Alzheimer’s disease is the most common neurodegenerative disorder and the leading cause of dementia worldwide. The generic term “dementia” is a descriptive one; it is used to define a decline in cognitive functions that is sufficiently severe as to cause social and occupational impairment. Non-cognitive symptoms, particularly behavioral and psychological, can also be manifestations of a dementing syndrome.
Alzheimer’s disease is characterised by gradually evolving pathological processes in the central nervous system, eventually leading to neuronal loss and brain atrophy. As these processes spread to wider areas of the brain, cognitive abilities become progressively worse. The most frequent initial symptom is deterioration of episodic (autobiographical) memory.
Alzheimer’s disease used to be referred to as “senile dementia”. Neurology has largely abandoned this term. It should be stressed that Alzheimer’s (and dementia in general) does not constitute a normal part of aging. Although its prevalence rises significantly among the elderly, it is nevertheless a neurodegenerative disease associated with distinct neurobiological changes. These changes seem to predate the onset of symptoms by a at least a decade and can, in rare cases, lead to disease onset before 60 years of age.
The socio-economic burden of Alzheimer’s is enormous, making it an emerging public health issue. Furthermore, its impact can spread beyond the quality of life of patients; often, the entire family or caregivers experience significant physical and psychological stress while providing care for a person affected with the disease.
There are currently no treatments that halt or reverse the biological changes that occur in the brains of persons with Alzheimer’s. There are, however, treatments that can mitigate the symptoms, improve patients’ quality of life and reduce the burden of the caregivers.
How common is Alzheimer’s disease?
The disease is observed in all societies and all races. Its prevalence is strongly age-related. Approximately 1% of the population aged between 65 and 69 is affected with Alzheimer’s. This percentage roughly doubles every 5 years.
- 1 in 9 people aged over 65 and almost 1 in 3 people over 85, suffer from Alzheimer’s disease.
- Approximately 80% of people with Alzheimer’s are older than 75.
- Given the increasing trend in life expectancy, a significant rise in the total number of patients is expected in the following decades.
Overall, Alzheimer’s disease constitutes 60% of all dementia cases. In Greece, it is estimated that at least 150.000 people are affected with dementia.
What are the stages of Alzheimer’s disease?
As mentioned, the neurodegenerative lesions that characterise Alzheimer’s develop gradually over an extensive period of time. The temporal evolution of the disease can be regarded as a process that goes through the following stages:
- Asymptomatic (preclinical) stage
This stage lasts many years (probably more than 10), during which there is progressive damage accumulation in specific parts of the brain. Despite various biological changes (amyloid and neurofibrillary tangles deposition, synaptic dysfunction, etc), the lesions are not severe enough to cause symptoms (or possibly the “reserve mechanisms” of the brain are able to counteract the deleterious effects). As a result, although people are congitively intact, their brains bear the biological hallmakrs of the earliest stages of the disease.
- Mild cognitive impairment (MCI)
During this stage lesions become more extensive, leading to the emergence of the first symptoms (usually impaired autobiographical memory). However, cognitive functions are largely preserved and therefore affected individuals are still able to perform adequately in their daily lives. It should be noted that mild cognitive impairment is a descriptive diagnosis with heterogeneous etiology (the cause is not always Alzheimer’s disease). The duration of this stage varies: it is estimated that 5% to 15% of mci patients convert to dementia every year.
- Clinically overt Alzheimer’s disease
Symptoms have become severe enough to cause social and occupational impairment. Cognition deteriorates, behavioral and psychological symptoms emerge and patients are in need of care and assistance. During the final stages, people with Alzheimer’s are completely dependent on caregivers, even for basic functions.
Evolution of histological changes in Alzheimer’s disease
During the asymptomatic stage, lesions (blue color) are restricted to a small part of the medial temporal lobe. This area plays an important role in the neural circuitry of episodic (autobiographical) memory. Histological changes progressively spread and finally involve extensive areas of the brain.
What are the symptoms of Alzheimer’s disease?
Symptoms develop gradually (usually over a few years) and progressively worsen. As a consequence, patients and their family members often find it difficult to pinpoint the exact time that the problems emerged. Sometimes, when the disease is still at a pre-clinical stage, confusion or delirium develops during an infection or a surgical procedure, lasting only a few days. This phenomenon may reflect the transient overwhelming of the rerseve mechanisms of an already vulnerable brain.
It is the most common presenting symptom and primarily involves episodic memory. This type of memory essentially expresses our ability to maintain a form of “mental autobiography”. We use it, for example, when we recall:
- conversations we had
- where we parked our car
- what we did last weekend
- where we put our keys
- what we ate for breakfast
Despite the fact that episodic memory ranges from minutes to years, it is the recent information that becomes more vulnerable when the neurobiological circuits are disrupted. A very common manifestation of this type of memory impairment is asking the same questions repeatedly. As the disease evolves, memory difficutlies become progressively more evident; patients have trouble keeping track of time (they may not remember the day, date, month or even the year) and other types of memory (non-episodic) become impaired as well.
Initially, symptoms usually manifest as a difficulty in finding words and a decline in verbal fluency. As the disease progresses, language impairment becomes more pronounced. Patients may become unable to keep track of conversations, their vocabulary is reduced and errors in spelling or grammar emerge. In advanced stages, even ordinary communication becomes difficult.
Visuospatial impairment tends to appear early in the course of Alzheimer’s disease. Patients experience difficulty orienting themselves, initially in unfamiliar and later in familiar areas. In advanced stages, they may have trouble finding their way even inside their own residence. These symptoms often coexist with impaired distance and speed perception. Visuospatial impairment increases the risk for wandering episodes.
Difficulties with planning and handling complex tasks
These symptoms indicate a decline in the brain’s executive functions. The latter are a group of higher regulatory and supervisory cognitive mechanisms that allow us to adapt to changing circumstances and adjust our behavior according to our goal. These symptoms are also associated with impaired judgement and loss of insight (lack of disease awareness).