The scope of the problem

The prevalence of dementia increases significantly with age, doubling every 5y after the age of 65y. The Canadian Study of Health and Aging noted that 8% of the population over 65y have dementia. This figure rises to over 34% in those 85y and older. The graph below outlines anticipated changes in prevalence within the next 20 years. The incidence of dementia increases steadily until 85 or 90y and then less rapidly thereafter. There are clearly significant economic impacts from the condition, in addition to it’s personal implications.

Projected prevalence of Alzheimer's disease or other dementia by age group, Canada, 2011 and 2031

What is dementia?

Now referred to as major neurocognitive disorder in the DSM V criteria, this is an acquired, progressive condition, affecting several different cognitive domains and severe enough to interfere with functional independence. The latter is clarified by assessing the patient’s basic activities of daily living (ADLs) and instrumental ADLS though a decline in the patient’s hobbies may be the 1st clue to a cognitive problem.

The exact presentation varies with the type of dementia but generally, there are impairments in memory (initially short term, but eventually long term memory too) with deficits in the ability to retain new information or remember details of events. In addition, the patient often develops language problems (word-finding difficulties), may have trouble recognizing people or places previously well-known to them, gets lost in familiar environments and has trouble with executive function. The latter may manifest as difficulty managing more complex multistep activities such as planning trips and events but eventually, even using the remote control for the TV may be challenging for them. Praxis problems (difficulty with skilled activities despite intact motor and sensory function) may be evident too e.g. dressing apraxia. A change in personality- more commonly, an exaggeration of previous traits but sometimes, a reversal of their previous personality- can also be seen.

Later on, behavioural problems and wandering make caregiving even more difficult.

DSM V criteria for Major neurocognitive disorder:

A.    Significant cognitive decline in ≥1 cognitive domain, based on:

• • 1.      Concern about significant decline, expressed by individual or reliable informant or clinician

    2.      Substantial impairment, documented by objective cognitive assessment

B.     Interference with independence in everyday activities

C.     Not exclusively during delirium

D.    Not better explained by another mental disorder

E.     Caused by 1 or more causal subtypes: Alzheimer’s disease, cerebrovascular disease, Lewy body dementia etc…

The cognitive domains involved include complex attention, executive function, learning & memory, language, perceptual-motor & social cognition.

Risk factors for dementia:

• • • Increasing age* (strongest risk factor)

    • Low education

    • Genetic factors- ApoE4, Downs syndrome, rarely familial Alzheimer’s  Disease in 3-5% of cases (mutations of amyloid precursor protein, presenilin 1 or 2)

    • Parkinson’s disease

    • Cardiovascular disease including heart failure, AF

    • Hypertension, High cholesterol, High BMI, diabetes mellitus in mid-life

    • Stroke

    • Obstructive sleep apnea

    • Depression & anxiety

    • PTSD

    • Head injury

    • Heavy alcohol consumption

Protective Factors for dementia:

• • • Genetic- ApoE2

    • Higher education

    • Cognitively stimulating activities

    • Physical activity

    • Mediterranean diet

What should you do next?

After a complete history from the patient and a reliable informant (including medication & alcohol review), a physical examination should be completed, with particular emphasis on the neurological exam. An objective cognitive assessment in the form of an MMSE or MoCA is helpful. Remember that this will be influenced by educational attainment. Looking at the pattern of deficits on these tests can help identify the subtype of dementia. The MMSE does not examine executive function well so the MoCA often complements it, as does the clock-drawing test. Judgement and insight should also be assessed at the bedside.

Rule out any potentially treatable disorders with screening lab-work including CBC, electrolytes, BUN, creatinine, B12, glucose, TSH, calcium and determine whether there is a concurrent mood disorder- very common in the early stages of the disease. Other lab-work may be required in specific circumstances e.g. liver function tests, HIV testing etc.

Whether or not to perform a CT scan (or less commonly) an MRI of the head will depend on the patient’s presentation and would be indicated in the following circumstances:

• • • Atypical cognitive symptoms or presentation

    • Age <60y

    • New unexplained neurologic symptoms or localizing signs

    • History of bleeding disorder or use of anticoagulants

    • Recent head trauma

    • History of cancer

    • Rapid decline in cognition or function (1-2 months)

    • Current gait disturbance

    • History of gait disorder or urinary incontinence early in dementia

    • Duration of dementia <2y

If the presence of unsuspected cerebrovascular disease would change clinical management MRI is more sensitive than CT for detecting atrophy and small vessel disease.

Functional neuroimaging in the form of PET and SPECT scans is increasingly available but tends to be reserved for cases of diagnostic difficulty or atypical dementias.

CSF sampling may be used to exclude infective, malignant & inflammatory conditions but is more typically done in the setting of rapid cognitive decline.

Analysis of CSF biomarkers such as β-amyloid & tau are increasingly mentioned in the literature and clinical trials but are not yet in routine clinical practice.

Management:

1.     Discuss the diagnosis.

2.     Treat any potential contributing factors- B12 deficiency, depression etc.

3.     Manage vascular risk factors.

4.     Address patient safety- is their current living situation appropriate for their needs? Are they safe to drive, manage their medications & finances, use the stove etc.  Does the patient wander? (think about a safely home alert bracelet, GPS devices). Are there behavioural problems?

5.     Consider medico-legal issues- have power of attorney or personal directive documents been created? This needs to be done whilst the patient still has capacity to name an agent.

6.     Is drug therapy a possibility? No cure exists yet but treatment to delay progression, help with word-finding, apathy and improve function is attempted using the acetylcholinesterase inhibitors. These increase cholinergic transmission at the synaptic cleft by preventing the breakdown of acetylcholinesterase, thereby inhibiting the breakdown of acetylcholine.

In the absence of contraindications, the cholinesterase inhibitors (donepezil, rivastigmine or galantamine) are used in the following dementias where cholinergic deficits are prominent:

• • • Alzheimer’s disease

    • Mixed Alzheimer’s & vascular dementia

    • Parkinson’s disease-related dementia 

    • Dementia with Lewy bodies

Contraindications to the cholinesterase inhibitors would include:

• • • Seizure disorder (they lower seizure threshold)                              

    • Angle closure glaucoma

    • Significant respiratory disease (they can cause bronchoconstriction)

    • Cardiac conduction problems (they can cause syncope or bradycardia)

    • Recent GI bleed (they increase gastric acid).

The main side effects of the cholinesterase inhibitors are nausea, vomiting or diarrhea. Obtaining an ECG prior to the initiation of therapy and with dose increases, is prudent given their potential to cause bradycardia and conduction problems.

Memantine is an NMDA receptor antagonist used in moderate-severe Alzheimer’s disease to counteract the effects of excess glutamate. It is used particularly in the presence of behavioural problems. Unfortunately, unlike the cholinesterase inhibitors, it is not covered by Blue Cross, so cost often precludes it’s use. Dizziness, diarrhea, headache and agitation are the main side effects. Caution is required in the presence of renal dysfunction or epilepsy.

When behavioural problems develop in the later stages of dementia, ensure that all potentially contributing factors have been addressed as agitation may be a manifestation of:                                                              

Medical illness     

Physical factors (constipation, poor sleep, pain, need for washroom, privacy..)          

Depression/anxiety or                                                   

Environmental factors (hot/cold environment, over/under-stimulation, poor approach by caregiver etc).

Ensure management of these conditions has been addressed. An ABC approach to identifying behavioural issues is often helpful.

• • • • • What are the Antecedents of the behaviour?

        • What is the Behaviour?

        • What are the Consequences of the behaviour?

After identifying the trigger for the behaviour, try to address the problem. For example, some patients with dementia will try and climb out of bed or scream when they need to toilet or have been incontinent. In this instance, having the nursing staff toilet the patient on a scheduled basis and changing them when they call out, can often help.

Other non-pharmacological approaches should be considered in the approach to management. This should be individualized e.g. some patients respond to reminiscence therapy, others to music though the evidence base for non-pharmacological management is limited.

In the setting of paranoid ideation or delusions that are distressing to the patient, antipsychotic medication is likely to be required. Use the lowest dose possible, preferably an atypical antipsychotic and ensure that it is not continued indefinitely as these problematic behaviours may not continue forever, but wane as the disease advances.

Other medications used in the management of behavioural problems in dementia include the SSRI antidepressants and trazodone.

6. Remember to consider the caregiver who is at increased risk of depression and often has had to curtail their own activities and frequently, their employment, to care for their loved one. Refer them to the Alzheimer’s society for support. 

Some of the more common types of dementia are described below:

Alzheimer’s disease:

This is the most common cause of dementia in Canada, accounting for 60-80% of cases. Classically, it is associated with gradually progressive memory loss. This is followed by visuospatial and executive difficulties but the memory loss is particularly prominent.

Atypical non-amnestic variants exist, though much less commonly, and present with language, visuospatial and executive problems.

Pathologically, it is characterized by amyloid plaques and neurofibrillary tau-containing tangles in addition to neuronal & synaptic loss with prominent cholinergic deficits. A progressive loss of nicotinic receptors has also been noted. Average survival from the time of diagnosis is around 10 years though this varies widely.

Vascular dementia:

This has a variable presentation depending on the location of the lesion. There is often early executive loss, personality and mood changes, gait and continence problems with less predictable memory involvement than would be expected in Alzheimer’s disease at a similar stage. It can develop gradually or in a stepwise pattern. There should be a temporal association with stroke or TIA, or evidence of neurologic deficits with neuroimaging evidence of large vessel infarcts, strategic infarcts, hemorrhage, extensive lacunar infarcts or white matter disease.

Frequently, vascular pathology coexists with Alzheimer’s pathology. It is then referred to as mixed dementia.

Frontotemporal dementia:

The patient presents earlier, often in the 6th decade. Men are affected more than women and there is progressive atrophy of the frontal or temporal lobes or both. FDG-PET  scans can be helpful diagnostically.

Frontotemporal dementia comprises 3 different clinical syndromes associated with progressive changes in behaviour and language. Memory and visuospatial skills are preserved early on.

1. behavioural variant (50% cases)-prominent early  changes in behaviour and personality - either disinhibited & socially inappropriate or passive & withdrawn. Each patient tends to be at one end of this spectrum though less commonly, they can fluctuate between the 2 extremes. Patients typically lack empathy towards others and insight into their deficits.

2. primary progressive aphasia, nonfluent variant- effortful, nonfluent speech. This may begin as a stutter& grammatical errors but word-finding difficulty becomes increasingly prominent.

3. primary progressive aphasia semantic variant- fluent aphasia, impaired word comprehension and semantic memory (memory for meaning). The patient’s speech is often empty and they seem very vague and their conversation doesn’t seem to make sense.

Be aware of the potential association of frontotemporal dementia with motor neuron disease, progressive supranuclear palsy and corticobasal degeneration.

Cholinesterase inhibitors are avoided in this condition as they often make the psychiatric difficulties worse. For pharmacological management of behavioural problems in frontotemporal dementias, a combination of SSRI antidepressants and/or trazodone is trialled.

Lewy body dementia:

This includes Parkinson’s-disease related dementia and Dementia with Lewy bodies. They are distinguished based on which comes 1st, the movement disorder (PD-related) or the cognitive deficits (DLB). Pathologically, it is characterized by Lewy bodies containing misfolded α-synuclein, a loss of dopamine and acetylcholine-producing cells and concomitant AD pathology.

In addition to a dementia characterized by prominent deficits in attention, visuospatial function & executive function (less memory problems early on), core features include fluctuating cognition, recurrent complex visual hallucinations & parkinsonism. REM sleep behaviour disorder is commonly present too.

These patients are very sensitive to the effects of neuroleptics so great caution is required in their prescription.

Alcohol-related dementia:

Executive, visuospatial & memory difficulties resembling Alzheimer’s Disease are seen but language function is usually spared. This usually occurs after years of alcohol abuse.

Cognitive improvement/ maintenance over time can occur with abstinence.

Parenteral thiamine should be administered to those with alcohol misuse disorders or suspected Wernicke-Korsakoff syndrome.

Other less common dementias may be seen in Normal pressure hydrocephalus (triad of cognitive impairment, urinary incontinence and gait difficulties), HIV, PSP and other neurodegenerative conditions.

Mild cognitive impairment or Mild Neurocognitive Disorder (DSM V):

Modest cognitive decline in one or more cognitive domains based on:

A.  1. Concern about mild decline, expressed by individual or reliable informant, or observed by clinician

     2. Modest impairment, documented by objective cognitive assessment

B. No interference with independence in everyday activities, although these activities may require more time and effort, accommodation, or compensatory strategies.

C. Not exclusively during delirium

D. Not better explained by another mental disorder

The cognitive domain most commonly affected is that of memory though non-amnestic MCI is also seen.

Although many with MCI remain stable over time, or even improve cognitively, annually, MCI progression to dementia is around 5-10%. There is currently no treatment for the disorder; trials of the cholinesterase inhibitors were not beneficial in several randomized controlled trials. Management of factors that may aggravate cognition- depression, certain medications etc- is useful.

Dementia is a devastating condition for the patient, caregiver and the health care system. It is likely to be encountered in all aspects of medical practice so understanding the condition and having an approach to it’s management is  important. Although no cure exists, addressing the patient’s care needs and identifying where support is required, is crucial. Many patients will need their physician to advocate on their behalf to ensure that optimal quality care is provided for them.

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