Dementia is an umbrella term that describes a progressive neurodegenerative disease characterized by cognitive decline causing an impairment in daily functioning.

Under this umbrella, we have multiple subtypes, including Alzheimer's, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia.

Neurodegeneration means that cells in the nervous system stop working and eventually die. This happens naturally as we age, but in dementia, there are abnormal changes that increase how many cells are lost.

This loss of neurons and their connections results in the symptoms described as cognitive decline, which is quite a general term.

It means an impairment in one of memory, executive function, language, attention, or visuospatial functions like recognizing faces or environments.

Since dementia is progressive, these can be seen to be getting worse over time. In the earliest stage, called the pre-dementia stage, there can be subtle symptoms such as anosmia, which is the loss of sense of smell.

This can occur as far back as 10 years before the first clinical signs of dementia. There can be mild cognitive impairment, but it does not impair daily functioning, which is a defining feature of dementia.

Examples could be some difficulty in finding occasional words or some forgetfulness. Once the symptoms are profound enough to cause impairment in daily function, it is called early stage dementia.

Here, symptoms are apparent to other people, such as forgetting to take medication, misplacing objects, difficulty in accomplishing tasks around the house, managing finances, as well as planning and organizing.

In the middle stage, people tend to lose the ability to acquire new information, particularly in Alzheimer's.

It's also here that they begin to require assistance with personal care and hygiene, and there can be more behavioral disturbances like restlessness, aggression, and repetitiveness.

They may also demonstrate a lack of insight into their condition, and problems with orientation also become more apparent.

In the later stages, people will believe that they are in a different time, commonly an earlier time in their life.

This is called time shifting, and patients may ask for people who are no longer alive. The ability to speak may be lost, regressing only to a few words.

Depression and anxiety become more common in the later stages, and hallucinations also become more prominent. Restlessness is very common at this stage, and aggression may be more present as it is more difficult for patients to express their needs.

Dangers like hot stoves may no longer be recognized, and faces or places also no longer recognized.

There can also be physical difficulties; walking becomes more difficult, leading to more time in chairs or in a bed, which predisposes to venous thromboembolism.

Nutrition is challenging as swallowing difficulties often develop, which can result in aspiration and ultimately pneumonia.

The duration of the timeline varies but tends to be roughly two years in each stage. Once functionally impaired, the most common subtype of dementia is Alzheimer's disease, which makes up around 70 percent of cases worldwide.

As with most subtypes, Alzheimer's is the result of accumulation of insoluble proteins in the brain.

There are two in particular involved in Alzheimer's. The first is beta-amyloid, which forms extracellular plaques, also known as extracellular senile plaques.

The second is hyperphosphorylated Tau protein, which accumulates inside neurons to form neurofibrillary tangles.

Beta-amyloid comes from the breakdown of a normal transmembrane protein called amyloid precursor protein. It is cleaved by alpha, beta, and gamma secretases, and is normally broken down.

But if the beta secretase acts first and is then followed by gamma secretase, this generates beta-amyloid and leads to the formation of the plaques.

These proteins lead to dysfunction and death of the neurons. They are found in normal brains; however, in Alzheimer's, there is a significantly higher quantity, and they're found in more particular locations, specifically the hippocampus, parietal, and temporal lobes.

Although dementia symptoms can generally be similar, the subtypes can have slightly different presentations.

Alzheimer's often presents with short-term memory loss and difficulty finding words. Visuospatial impairment is also fairly common, for example, getting lost and problems with insight, meaning they do not realize that they have problems with their memory.

Vascular dementia makes up around 15 percent of cases and generally involves disturbance in the blood supply to the brain, leading to ischemia and loss of cells.

If the blood supply to the brain is interrupted, causing the neurons to die, this could be called a stroke.

And it is thought that in vascular dementia, there could be a series of small strokes which alone are not evident, but as they increase in number, the symptoms then develop.

This is known as multi-infarct dementia. Subcortical dementia is another common type of vascular dementia in which the smaller penetrating vessels are affected, sometimes called small vessel disease.

Because of the close link to strokes, it's no surprise to have a stroke-related subtype of vascular dementia, with up to 30 percent of patients with ischemic strokes estimated to go on and develop vascular dementia.

In the periods between events, there may be little to no decline, followed by sudden decline when new insults occur. This gives vascular dementia the characteristic stepwise progression.

Risk factors include smoking, diabetes, atrial fibrillation, dyslipidemia, hypertension, and age, with the risk doubling every five years.

In vascular dementia, impairments in planning, organizing, and judgment are noticeable early on. Lewy body dementia is seen in around 10 percent of cases.

Lewy bodies are spherical deposits with surrounding fibers found in the cytoplasm of neurons. The center of the deposit is formed from alpha-synuclein and ubiquitin aggregates.

Lewy bodies are also a primary brain abnormality in Parkinson's disease dementia.

Lewy body dementia has core symptoms such as fluctuating cognition, visual hallucinations, and Parkinsonian symptoms like bradykinesia, which is the slowing of movements, cogwheel rigidity, a predisposition to falls, and autonomic disturbances like orthostatic hypotension, incontinence, and constipation.

It also has suggestive symptoms like REM sleep disturbance or antipsychotic sensitivity. One or more core with one or more suggestive symptoms is enough for a probable diagnosis, while having only one or more suggestive gives a possible diagnosis.

The second most common dementia in people under the age of 65 is frontotemporal dementia, just behind early Alzheimer's, with the mean age of onset being 53.

Experts believe that there are two main disease processes involving transactive DNA binding protein TDP-43 and the microtubule-associated Tau protein.

Behavioral variant type is the most common subtype, characterized by personality changes and behavioral changes like disinhibition and social withdrawal occurring early on in the process.

Spherical collections of Tau fibrils can be found in the cytoplasm called Pick bodies, which is why frontotemporal dementia was in the past called Pick's disease.

Semantic variant manifests with language difficulties, including difficulties in finding words, as well as impairments in comprehension. This variant features a form of fluent aphasia.

Non-fluent primary progressive aphasia features labored, hesitant speech rather than fluency. And these two are under the category of primary progressive aphasia.

Increasing age is generally the largest risk factor. At age 65, there is a 2% prevalence, while at 85, it is as high as 40%.

Genetics also has a role. For example, a family history of a first-degree relative with Alzheimer's increases the risk by between 10 and 30%.

Early-onset dementia is defined as dementia affecting people under the age of 65, which makes up around 5% of all cases.

Trisomy 21, or Down syndrome, is a significant risk factor for developing early-onset Alzheimer's.

There are three chromosomes instead of two, which could mean more amyloid precursor protein and therefore more beta-amyloid being produced. In Alzheimer's, there can be autosomal dominant transmission with near complete penetrance.

This is the case in around 5% of all cases and in most cases of early- onset Alzheimer's.

For the early-onset variant, the three genes in particular are amyloid precursor protein on chromosome 21, presenilin 1 and 2 on chromosomes 14 and 1.

For later-onset Alzheimer's, apolipoprotein E genes play a larger role. It is a regulator of lipid metabolism and can interact with beta-amyloid.

The E4 variant is thought to produce a 50% risk of developing Alzheimer's, while having two alleles is thought to produce a 90% risk.

Dementia in general is more common in women, but this may be because women tend to live longer than men. Cognitive reserve is another factor. It is the extent of neuronal loss that can be tolerated before function is impaired.

People who are socially isolated or left education early or have low job complexity typically have a lower reserve and are therefore more likely to develop dementia.

We've also already mentioned risk factors for vascular dementia.

The only conclusive diagnostic test for Alzheimer's is a brain biopsy and histological confirmation, which is rarely done in living people.

Some imaging techniques like positron emission tomography or PET scans are being developed that can detect these histological findings non-invasively.

Therefore, the clinical history alongside a largely normal neurological exam is most commonly how dementia is suspected. A mental state examination is done to evaluate cognition, examples being the Mini-Mental State Exam and the Montreal Cognitive Assessment.

Blood tests are usually normal; however, there are some reversible causes of cognitive impairment that can be detected, such as vitamin B12 or folate deficiency, hypothyroidism, electrolyte disturbance like hypocalcemia, and even infective causes like Lyme's disease and neurosyphilis.

CT imaging can help to rule out other causes of cognitive impairment and may also reveal cerebral atrophy, meaning a shrinking in the brain volume.

Although this is suggestive, it is not specific for dementia.

Genetic tests are not routinely done, and this is mostly reserved for rare familial forms. No cure currently exists for dementia.

The one-year mortality is 30 to 40%, while the five-year mortality is around 65%. The most common cause of death is pneumonia, which may be because swallowing problems can predispose to aspiration and subsequently pneumonia.

Some medications are used to reduce the symptoms, such as cholinesterase inhibitors, which prevent the enzyme cholinesterase from breaking down acetylcholine, a neurotransmitter.

involved in cognition and memory. Examples include donepezil, galantamine, and rivastigmine. NMDA receptor antagonists like memantine are also used.

These two classes have been found to slow the cognitive decline, but the effect on overall survival is not yet conclusive. In vascular dementia, a key part of management is addressing identified risk factors, which may help in slowing the progression.

Behavioral and environmental approaches are encouraged, for example, maintaining a familiar environment, monitoring personal comfort, and redirecting attention.

People with dementia are also prone to developing anxiety, depression, or even psychosis, and it is also important to treat these symptoms as well.

Regular aerobic exercise has been found to slow down the progression of Alzheimer's disease.

Understanding Dementia (Alzheimer's & Vascular & Frontotemporal & Lewy Body Dementia)

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