Differentiating Causes of Dementia

Globally, approximately 50 million people have dementia, and there are nearly 10 million new cases every year.

Dementia is a syndrome in which there is deterioration in memory, thinking, behaviour and the ability to perform everyday activities. Although dementia mainly affects older people, it is not a normal part of ageing. In rarer cases, it can also affect younger people.

There are several different causes of dementia, all of which have overlapping features, which can cause confusion when making a diagnosis. For this reason, they are a common topic in medical exams. In this exam tips article, we will look at some of the more commonly tested one and highlight the features that will help you to ascertain the most likely diagnosis.

Alzheimer’s disease

Alzheimer’s disease is the most common cause of dementia, accounting for around 50% of all cases. It involves progressive degeneration of the cerebral cortex, with cortical atrophy, neurofibrillary tangles, amyloid plaque formation and reduction in acetylcholine production from affected neurons. The cause is not yet fully understood.

The onset of Alzheimer’s disease is typically gradual and insidious. It progresses slowly over 7-10 years with different symptoms being present depending on the stage of the disease.

In the early stages of Alzheimer’s disease, the patient is frequently noticed to be forgetful by relatives and friends, with lapses in memory evident. Forgetting the names of people and places and having difficulty finding words for things is commonly seen. The patient also often cannot remember recent events and forgets appointments. As the disease progresses, difficulty with language skills and problems with planning and decision making develop. Apraxia can occur, and the patient is noticed to be more obviously confused.

In the later stages, symptoms include wandering, disorientation and apathy. Psychiatric symptoms also develop in this stage, with depression being common. Psychotic symptoms, such as hallucinations and delusions, may also be seen. Late in the disease, there may also be behavioural problems, such as disinhibition, aggression, agitation, and this can be very distressing for the family.

Vascular dementia

Vascular dementia is the second leading cause of dementia, accounting for around 25% of all cases. It involves damage to the brain caused by a variety of different mechanisms, including major strokes, multiple smaller unrecognised strokes (multi-infarct) or chronic changes in smaller vessels (subcortical dementia). Increasingly the term vascular cognitive impairment (VCI) is used to encompass this spectrum of disease.

In contrast to Alzheimer’s disease, which is characterised by a slow and insidious onset, vascular dementia can occur suddenly and typically has a series of stepwise increases in symptom severity. The presentation can vary significantly, though, as can the speed of progression.

Features that are more suggestive of a vascular cause of dementia include:

History of TIAs or cardiovascular disease
Presence of focal neurological abnormalities
Prominent memory impairment in the early stages of disease
Early presence of disturbance in gait and unsteadiness
Frequent, unprovoked falls in early stages
Bladder symptoms (e.g. incontinence) without a demonstrable urological condition in early stages
Seizures

Dementia with Lewy bodies (DLB)

Dementia with Lewy bodies (DLB), which is also referred to as Lewy body dementia (LBD), is a progressive neurodegenerative dementia that is closely associated with Parkinson’s disease (PD). It is the third most common cause of dementia in the elderly after Alzheimer’s disease and vascular dementia, accounting for approximately 15% of cases.

The clinical features of DLB include:

Mild features of Parkinsonism or co-existing PD
Progressive decline in cognitive function
Fluctuations in cognition, alertness and attention span
Episodes of transient loss of consciousness
Recurrent falls
Visual hallucinations
Depression
Complex, systematized delusions

The level of cognitive impairment often fluctuates from hour-to-hour and from day-to-day.

Pathologically DLB is characterized by the development of abnormal collections of protein within the cytoplasm of neurons (Lewy bodies). These intracellular protein collections have similar structural features to the ‘classical’ Lewy bodies seen in Parkinson’s disease:

Image sourced from Wikipedia
Courtesy of Dr. Andreas Becker CC BY-SA 3.0

Frontotemporal dementia

Frontotemporal dementia is a progressive dementia, typically affecting the frontal and/or temporal lobes. This is now considered part of an overlapping collection of syndromes which are more common than has been thought in the past. One type of frontotemporal dementia is Pick’s disease. Pick’s disease (PiD) and frontotemporal dementia/degeneration should not be used interchangeably though, as PiD is only one type of frontotemporal dementia syndrome.

Pick’s disease is a rare neurodegenerative disorder that causes a slowly progressive frontotemporal dementia. A defining characteristic of the disorder is the build-up of tau proteins in neurons, accumulating into silver-staining, spherical aggregations referred to as ‘Pick bodies’.

The usual age of onset is between 40 and 60 years of age. It is initially characterized by personality changes such as:

Disinhibition, tactlessness and vulgarity
Changes in moral values
Efforts to dissociate from family
Problems with concentration
Over-activity, pacing and wandering

The changes in personality occurring before memory loss allow Pick’s disease to be distinguished from Alzheimer’s disease. As the disease progresses the patient will develop deficits in intellect, memory and language.

Huntingdon’s disease

Huntington’s disease (HD) is an autosomal-dominant inherited, progressive neurodegenerative disorder characterised by a distinct phenotype, including chorea and dystonia, incoordination, cognitive decline and behavioural difficulties.

The disease is associated with increases in the length of a cysteine-adenosine-guanine (CAG) triplet repeat present in a gene called ‘huntingtin’ (HTT) located on chromosome 4p16.3. Expression of this gene results in multiple cellular changes including cell loss with the basal ganglia and cerebral cortex.

The disease usually presents between 30 and 50 years of age, but it can manifest at any age. There is often a prodromal phase of mild psychotic and behavioural symptoms that occurs prior to the development the development of chorea.

Early signs of HD include personality changes, self-neglect, apathy with clumsiness, fidgeting with fleeting facial grimaces. Behavioural problems can occur and may lead to family conflict, marital breakdown and job loss before a formal diagnosis has been made.

HD then leads to progressive chorea, rigidity and dementia. It is frequently associated with seizures. Chorea is initially mild but may be severe and cause uncontrollable limb movements.

As the disease progresses, chorea is gradually replaced by dystonia and Parkinsonian features. Dysarthria, dysphagia and abnormal eye movements are common.

Pseudodementia

Pseudodementia, also sometimes referred to as depression-related cognitive dysfunction, is a condition in which there is a temporary decline in cognitive function in combination with a functional psychiatric condition.

Depression is most commonly the cause, but it is seen in a wide range of psychiatric conditions including schizophrenia, bipolar disorder and hysteria. It is reversible with treatment of the underlying psychiatric condition. It is associated with a relatively high-risk of suicide.

Features that are consistent with a diagnosis of pseudodementia include: