Alzheimer's Disease: What It Is, Causes, Symptoms, Stages, Treatment & More

1. Early-Onset Alzheimer's Disease It is a rare type of Alzheimer's disease where the symptoms start before the age of 65. It can even affect people in their 40s or 50s; however, it only makes up under 10% of all Alzheimer's cases. Early-onset Alzheimer's is often connected to genetic alterations, especially in three genes: APP, PSEN1, and PSEN2. If there's a family history of early-onset dementia, the risk increases significantly.

2. Late-Onset Alzheimer's Disease It usually affects people aged 65 years or above. The exact reason is still not fully known, but it may result from a combination of genetic factors, lifestyle choices, and environmental exposures. The apolipoprotein E (APOE) ε4 gene is considered the biggest known genetic risk factor for late-onset Alzheimer's.

1. Stage 1: Preclinical Alzheimer's Disease At this point, there are no clear visible symptoms. Still, changes in the brain, like amyloid plaque build-up, may already be occurring even if no one can feel them yet. They are usually only detectable through specialised biomarker testing. This stage can start years, and sometimes decades, before any symptoms show up.

2. Stage 2: Mild Cognitive Impairment (MCI) Due to Alzheimer's

   At this stage, people tend to notice subtle shifts in memory. Sometimes the person themselves notices the change or a close family member does, but daily life is not disrupted in a major way. They might:

   • Forget recent conversations or appointments more often than before.
   • Misplace items occasionally.
   • Have slight trouble finding words.

   It is important to note that not everyone with MCI goes on to develop Alzheimer's dementia.

3. Stage 3: Mild (Early-Stage) Alzheimer's Dementia

   At this stage, symptoms become more noticeable and start to affect everyday functioning. Typical signs include:

   • Forgetting the names of acquaintances.
   • Losing things or misplacing objects.
   • Difficulty handling problem-solving or other complex tasks.
   • Getting disoriented even in familiar places.
   • Repeating the same questions.
   • Changes in mood and personality, such as social withdrawal or a mild amount of anxiety.
4. Stage 4: Moderate (Middle-Stage) Alzheimer's Dementia

   This stage can feel like it drags on the most, sometimes for years. You might notice symptoms like:

   • Major memory issues, including not remembering parts of personal history.
   • Confusion about what day it is, or even the time and location.
   • Trouble handling money.
   • Completing tasks that involve several steps.
   • Difficulty recognising close relatives, even if they've known them for ages.
   • Changes in character and behaviour, for example, suspiciousness, agitation, or wandering off.
   • Sleep that gets messed up, with unusual or broken patterns.
5. Stage 5: Severe (Late-Stage) Alzheimer's Dementia

   This is the last stage, in which the illness has progressed to a point where the patient requires full-time care. They may:

   • Gradually lose the ability to talk verbally.
   • Struggle with basic self-care, like eating, dressing, or bathing, without help.
   • Experience loss of control over some body functions.
   • Be at a higher risk for infections, especially pneumonia.
   • Spend a lot of their time lying in bed.

   There is no cure yet at any stage, though treatment, along with supportive care, can help manage the disease during its progression.

1. Memory and Thinking-Related Symptoms

   • Trouble remembering newly learned things, names, or recent events
   • Asking the same questions over and over
   • Getting disoriented in places that should feel familiar
   • Trouble with problem-solving, organising, or finishing everyday tasks they used to manage
   • Confusion about dates, seasons, and how time is passing
   • Difficulty finding the right words or keeping up with conversations
   • Poor judgment or decision-making
2. Behavioural and Mental Symptoms

   • Pulling back from friends, social life, and hobbies
   • Mood changes, such as depression, anxiety, and irritability
   • Suspicion, paranoia, or even delusions
   • Restlessness that tends to show up later in the day is sometimes referred to as "sundowning"
   • Wandering around, or ending up lost
3. Physical Symptoms (Usually Later On)

   • Struggling to swallow or to eat properly
   • Loss of bladder and bowel control
   • Lower mobility and a higher chance of falls
   • Noticeable weight loss

   It is important to note that a bunch of these signs are not specific to Alzheimer's only; they can also come from other medical issues.

1. Biological Causes

   • Amyloid plaque buildup: Pieces of amyloid protein end up sticking together, forming plaques between neurons, and that starts messing with normal cell-to-cell communication.
   • Tau tangles: An abnormal tau protein ends up twisting, then gathers into tangles inside neurons, which can interfere with the movement of nutrients and eventually contribute to neuron loss.
   • Neuroinflammation: Long-term inflammation throughout the brain is increasingly recognised as one of the major drivers behind Alzheimer's progression.
   • Lower acetylcholine: The drop of this neurotransmitter, which supports memory and learning, is often treated as a signature feature of the disease.
2. Genetic Causes

   • The APOE ε4 gene is considered the biggest genetic risk factor for late-onset Alzheimer's. Risk tends to rise; with two copies, risk rises even more.
   • Mutations in the APP, PSEN1, and PSEN2 genes can lead to familial early-onset Alzheimer's disease.

3. Lifestyle and Environmental Factors These typically do not directly “cause” Alzheimer's, but they do increase the likelihood of developing it.

1. Non-Modifiable Risk Factors

   These are the things you cannot really change, no matter how much you try:

   • Age: Often the greatest known risk factor. Generally, the risk roughly doubles every five years after you turn 65.
   • Family history and genetics: If you have a first-degree relative with Alzheimer's, your chances to get the disease increase quite a lot.
   • Reduced Estrogen: The sharp decline of neuroprotective estrogen during the menopausal transition leaves the female brain vulnerable to accelerated metabolic decline and inflammation.
   • Down syndrome: Many people with Down syndrome tend to develop Alzheimer's disease at an earlier point in life.
2. Modifiable Risk Factors

   The 2024 Lancet Commission examined 14 modifiable risk factors that could, when combined, account for up to 45% of dementia cases around the world:

   Early Life:

   • Lower levels of education

   Mid-Life:

   • Hearing loss
   • High LDL cholesterol
   • Depression
   • Traumatic brain injury
   • Physical inactivity
   • Diabetes
   • Smoking
   • High blood pressure (hypertension)
   • Obesity
   • Excessive alcohol consumption

   Late Life:

   • Social isolation
   • Air pollution exposure
   • Untreated vision loss

This finding is significant because it means that nearly half of all Alzheimer's cases could potentially be prevented or delayed through lifestyle changes and timely medical intervention.

1. Medical History And A Cognitive Check The doctor goes through the patient's medical history, medications, and family history. Then there are standardised cognitive tests, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). These are meant to look at memory, language, the ability to solve problems, plus attention.

2. Blood Tests Blood tests can help rule out other, more treatable reasons for cognitive decline. For example, thyroid disorders, vitamin B12 deficiency, or infections. More recently, blood-based biomarker tests aimed at Alzheimer's-specific proteins, such as plasma pTau231, are being talked about as useful for earlier detection.

3. Brain Imaging

   • MRI (Magnetic Resonance Imaging): It can show brain shrinkage, called 'atrophy', mainly in the hippocampus, which is basically the brain's memory centre, and it can also help rule out strokes or tumours.
   • CT (Computed Tomography) Scan: A CT scan provides a quick view of brain structure, like an overview.
   • PET (Positron Emission Tomography) Scan: PET scans can show amyloid plaques and tau tangles directly in a living brain. According to more recent diagnostic criteria, amyloid PET and tau PET have become central for getting an accurate diagnosis of Alzheimer's.

4. Cerebrospinal Fluid Analysis A lumbar puncture, also called a spinal tap, can measure amyloid and tau levels in the cerebrospinal fluid. When the results are abnormal, it's a strong sign of Alzheimer's disease.

5. Neuropsychological Testing A detailed evaluation by a neuropsychologist assesses memory, language, thinking skills, and other cognitive abilities in more depth than the usual screening tests.

1. Cholinesterase Inhibitors

   These drugs raise acetylcholine levels in the brain, so neuron-to-neuron communication works a bit better. They're typically given for mild to moderate Alzheimer's and include:

   • Donepezil (used across all stages)
   • Rivastigmine
   • Galantamine

2. NMDA Receptor Antagonist Memantine is used when the disease becomes moderate to severe. It helps regulate glutamate activity in the brain, which contributes to learning and memory. Still, these options are not a cure; they only slow the disease slightly, and can have side effects, too.