Alzheimer’s disease (AD) is a neurodegenerative disorder, meaning a disorder that causes degeneration of the brain cells. AD is characterized by gradual (insidious) onset and progressive impairment of cognitive functions and behavioral changes. It is identified as one of the significant causes of dementia. These functions include memory, comprehension, language, attention, reasoning, and judgment. They also manifest behavioral symptoms like depression, anxiety, anger, irritability, insomnia, and paranoia. With disease progression, affected individuals may even require assistance with their activities of daily living.

AD typically manifests after age 65 and is referred to as late-onset AD (LOAD). However, early-onset AD (EOAD), occurring before 65, is less common and seen in about 5% of AD patients. The prevalence of AD doubles every five years after the age of 60, increasing from a prevalence of 1% among those 60- to 64 years old to up to 40% of those aged 85 years and older. The disease is more common among women than men by a ratio of 1.2 to 1.5.

Risk factors such as increasing age, head injuries, vascular diseases, infections, and environmental factors play a role in the disease. Many times, genetic factors play a crucial role. Multiple genes are now linked with the early onset of AD. Family history of AD or dementia, fewer years of formal education, lower income, and lower occupational status are also found to be risk factors for AD.

Clinically, AD is classified into the following stages:

1. Pre-clinical or the pre-symptomatic stage – This stage is characterized by mild memory loss with no functional impairment in daily activities and the absence of clinical signs and symptoms of AD and may last for several years.

2. The mild or early stage of AD – During the mild stage, several symptoms start to appear in patients, including a loss of concentration and memory, mood and behavioral changes, and disorientation of place and time, creating trouble in the daily life of the patient that may result in the development of depression.

3. Moderate AD stage – The moderate stage presents as increased memory loss with trouble recognizing family and friends, a loss of impulse control, and difficulty in reading, writing, and speaking.

4. Severe AD or late-stage – In this stage, there is a progressive functional and cognitive impairment where the patients cannot recognize their family at all and may become bedridden. They also develop difficulties in swallowing and urination. The complications eventually worsen and lead to death.

Pathologically, there is increased deposition of abnormal protein in certain brain areas. These are called neuritic plaques and neurofibrillary tangles, which exceed the anticipated limits for age-matched healthy controls. These results in neurotoxicity and tau pathology induction, consequently leading to neuronal cell death and neurodegeneration. Several gene mutations, including APP, PSEN1, and PSEN2, have established risk factors for AD, affecting Aβ catabolism and anabolism, resulting in Aβ accumulation and faster progression of neurodegeneration.

Unfortunately, AD has no cure, and its progression varies from person to person. Early diagnosis of AD remains challenging, as there is no definitive test. Diagnosis is clinical based on symptoms and clinical findings, excluding other causes. Blood tests and brain imaging are done to rule out other causes. As there is no specific treatment, symptomatic treatment remains the primary approach in everyday clinical practice.

A few tips and precautions for effective management or delaying the progression of AD

Dietary Considerations – Include nutritional supplements like certain vitamins, antioxidants, polyphenols, and fish to decrease the risk of AD – Avoid saturated fatty acids and high-calorie intake, as these increase the risk of AD. – Try following a Mediterranean diet (MD)

Physical Activity – Regular physical activity improves brain health and reduces the progression of AD by stimulating brain vascularization, plasticity, and neurogenesis, thereby reducing inflammation by decreasing Aβ production. – Physical activity delays the onset of dementia and improves cognition and executive functioning in older individuals. Improved cognition and executive functioning help reduce the fall risk and enhance the ability to perform activities of daily living. – Physical activity reduces the incidence of neuropsychiatric symptoms like depression.

Intellectual activity and higher education may also reduce AD progression and memory loss.

(This article is authored by Dr. Poonam ChandrashekharAwatare, Consultant – Neurology, Manipal Hospital Varthur Road)