Alzheimer’s disease
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder; overtime it gradually damages and destroys brain cells. It is the most common type of dementia, responsible for about two-thirds of dementia cases in people aged 65 years and older.
AD leads to memory loss and other cognitive impairments, including problems with language, learning, memory, visuospatial abilities, behavior, reasoning and thinking. As the disease progresses, these symptoms become more severe and interfere with daily activities such as managing finances, cooking, or remembering appointments.
AD is mainly identified by the presence of two abnormal protein accumulations in the brain, neurofibrillary tangles inside neurons and amyloid-beta plaques outside neurons. These abnormal protein aggregates damage neurons and disrupt brain communication, leading to cognitive decline.
Symptoms of Alzheimer’s disease
AD is a common neurodegenerative brain disorder that usually occurs sporadically. It can develop without any clear family history. AD may lead to
- Progressive loss of brain tissue
- Shrinking (atrophy) of the cerebrum
- Loss of neurons (nerve cells)
Damage mostly occurs in the area such as hippocampus, and medial temporal lobe. Both are responsible for memory formation and learning, which is why memory loss is one of the earliest symptoms of AD.
Early Symptoms Develop Gradually- Early symptoms develop gradually and slowly such as, forgetting recent conversations, repeating questions, misplacing objects.
Certain Events May Reveal Hidden Disease- After stress or medical treatment, sometimes some of the underlying disease process becomes noticeable such as fever, traumatic brain injury, surgery and starting new medication. These events don’t cause Alzheimer’s directly, but they may trigger AD symptoms in someone who already has early brain changes.
Alzheimer’s Disease Continuously Worsens- A key feature of Alzheimer’s disease is that the progression does not stop. There is no plateau stage where the disease remains stable. Symptoms gradually worsen over time.
If a patient’s symptoms do not worsen for a long period, there is possibility of other brain disorders which mimic AD symptoms, such as:
- Frontotemporal Dementia
- Normal Pressure Hydrocephalus
- Binswanger Disease
- Temporoparietal embolic infarcts (stroke-related brain damage)
Final Stage And Cause Of Death- In advanced stages, patients become severely debilitated. They lose the ability to walk, communicate, or care for themselves and many become bedridden. Death usually occurs due to complications such as cardiovascular problems, respiratory or pulmonary infections (e.g., pneumonia) and severe physical weakness. Thus, patients usually do not die directly from Alzheimer’s disease itself, but from complications caused by the advanced stage of the illness.
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Detail Explanation of AD Symptoms
What is EOAD and LOAD?
EOAD (Early-Onset Alzheimer’s Disease)
Early-Onset Alzheimer’s Disease (EOAD) is Alzheimer’s disease that develops before the age of 65. In EOAD, symptoms usually start between 30–65 years and strongly linked to genetic mutations. EOAD accounts for only 5–10% of all Alzheimer’s cases.
The common genes involved in EOAD are APP (Amyloid Precursor Protein), PSEN1 (Presenilin-1) and PSEN2 (Presenilin-2). These are the three major genes known to cause Alzheimer’s disease, especially Early-Onset Alzheimer’s Disease (EOAD). These genes are involved in the production and processing of amyloid-β peptides, which accumulate in the brain and form plaques.
Symptoms are similar to typical Alzheimer’s but may progress more aggressively, including:
- Memory loss
- Language problems
- Difficulty with planning and reasoning
- Behavioral changes
LOAD (Late-Onset Alzheimer’s Disease)
Late-Onset Alzheimer’s Disease (LOAD) is Alzheimer’s disease that develops after age 65. It is most common form of AD and accounts for 90-95% of all AD cases.
LOAD does not follow a simple inheritance pattern and results from a complex interaction of factors. The most common genetic factor responsible for LOAD is APOE gene, especially the ε4 allele. Environmental and lifestyle factors such as aging, cardiovascular diseases, diabetes, obesity, smoking and physical activity are the other important risk factor of LOAD.
Memory Problem is the most common symptom
Loss Of Short-Term Memory and Episodic Memory– About 90% of people with Alzheimer’s disease show memory problems. The first type of memory affected is short-term memory and episodic memory. In early Alzheimer’s, patients forget these recent events easily, and sometimes memory loss may be the only symptom for several years.
Common Real-Life Symptoms- Because of short-term memory problems, patients may show behaviors such as:
- Forgetting appointments or scheduled meetings
- Misplacing household items like keys or glasses
- Repeating the same questions again and again
- Having unclear or incomplete conversations
- Difficulty following discussions
No Effect On Working (immediate) Memory- Working memory may remain normal initially. working memory is the ability to hold information briefly and use it, such as remembering a phone number for a few seconds, following simple instructions and focusing on a conversation.
In the early stage of Alzheimer’s, this type of memory is often relatively preserved because it mainly depends on attention.
Long-Term Memory Declines In Later Stages– Long-term memory includes memories stored for months or years, such as childhood memories, names of family members, important life events. In late stages of Alzheimer’s, long-term memory becomes severely damaged, but early-diagnosed patients may not show major long-term memory loss yet.
Changes in behavior or personality
In AD, there is noticeable changes in their personality and behavior, , and these changes may occur together with cognitive symptoms (like memory problems) or sometimes even before them.
Personality Changes– Changes in behavior or personality can happen at the same time as memory or thinking problems, or occasionally appear earlier. The person may become more anxious, worried, emotionally unstable, or easily stressed. They become less social, quieter, or more withdrawn.
AD patients show less interest in new ideas, experiences and activities. They get easily irritated, less cooperative, lack of self-discipline and lack of responsibility.
Language Problems Appear After Memory Problems
Problem in language is usually developed after memory impairment becomes severe, because patients cannot recall the correct word, they may hesitate while speaking, pause frequently, repeat the same words and use limited vocabulary. This condition is called word-finding difficulty.
Due to reduced word variety, patients may repeat the same words again and again, use stereotyped expressions (fixed phrases repeatedly).
Writing ability may also declines in AD patients due to language impairment. This occurs because the same brain regions involved in speech are also involved in writing.
At first, language problems may be subtle and difficult to detect, but as AD progresses, speech becomes fragmented, sentences become short or incomplete and patients pause frequently while searching for words and communication becomes very difficult to understand.
Language disorders in later stages– Two important language abnormalities can appear like, echolalia and anomic aphasia. This type of language abnormalities is common in AD.
Logopenic variant primary progressive aphasia (lvPPA) – In rare cases, language problems appear before memory problems. This condition is called Logopenic variant primary progressive aphasia (lvPPA). In lvPPA, word-finding difficulty is the first symptom, language ability gradually worsens and later, typical Alzheimer’s symptoms develop.
Dyscalculia – Patients may develop dyscalculia, meaning difficulty performing calculations and managing money.
Altered decision-making– Patients may also show changes in judgment and decision-making. They have difficulties in making financial decisions, planning tasks and reduced ability to evaluate consequences. These problems occur because Alzheimer’s gradually damages brain areas responsible for executive functions, such as the frontal and parietal regions.
In Early Onset of Alzheimer’s disease, patients often develop disorientation to time and place. They may become confused about dates, seasons, or locations. Damage to the brain’s visual-spatial processing areas can also cause visuospatial disorientation, leading to problems with navigation, face recognition, and everyday tasks like dressing or driving.
Functional and executive disturbances
In Alzheimer’s disease, functional and executive disturbances are among the most disabling symptoms. Functional and executive disturbances mean the loss of ability to perform daily activities and difficulty in planning, organizing, and making decisions due to brain dysfunction.
Patients start having difficulty with learning new information, performing complex tasks, coordinating multiple activities, and following complicated instructions,
Psychological and social consequences- Because patients realize they are losing their abilities, this can lead to low self-esteem, withdrawal from social activities, depression, resignation or hopelessness and financial problems (due to inability to manage work or money)
Locomotor abnormalities- Locomotor abnormalities (movement problems) may also appear in AD patients. The most common early change is slower walking speed, poor balance, slow gait, longer time with feet on the ground while walking (increased stance time), shorter step length. These changes increase the risk of falls.
In advanced stages of Alzheimer’s disease, patients may develop symptoms similar to those seen in Parkinson’s disease, including fine tremors, and muscle rigidity.
Loss of sensation
Some of the AD patients may have reduced sensory perception. The brain becomes less able to filter and process sensory signals (called sensory gating deficit). The loss of sensation is due to cholinergic neurons damage and loss of α7 nicotinic receptors.
AD patients may not feel pain either. Their pain tolerance increases, become weaker or delayed.
Primitive reflexes disappear
Later in the disease, primitive reflexes that normally disappear in infancy may reappear such as grasp reflex (automatically grabbing objects), and sucking reflex. This indicates severe brain damage.
Abnormal eye movements
AD patients may show slower and less accurate eye movements such as, quick eye movements between objects (Saccades) become slower, tracking moving object with eye (Smooth pursuit) become less accurate and small eye movement (microsaccades) and pupil dilation patterns may also change.
AD may affect several parts of the visual system, including optic nerve and retina.
Visual problem is early symptoms of AD patients, they develop visual impairments early in the disease, including:
- Reduced contrast sensitivity
- Reduced color sensitivity
- Limited visual field
- Poor visual attention
- Reduced stereopsis (depth perception)
- Difficulty recognizing objects and faces
Tremors and involuntary movements
In AD patients, tremor can occur, but it is rare and not strongly related to disease progression. As the disease progresses, other motor symptoms become more common, such as:
- Reduced speech and facial expression
- Muscle rigidity
- Problems with posture and walking (gait)
- Bradykinesia (slowness of movement)
Loss of bladder and bowel sphincter control
Patients may also lose sphincter control, meaning they cannot control urination and bowel movements. This is called incontinence.
In the advanced stage, walking and standing become difficult, patients become bedridden.
they may enter a vegetative state. At this point, patients require continuous caregiver support and medical care.
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