Psychiatry

Cognitive ageing

Cognitive, or thinking, ability is the product of:

‘Fixed intelligence’, the result of previous thinking, which often increases with age, ie ‘wisdom’
‘Fluid intelligence’, ie real-time information processing, which declines modestly in older age

There are structural changes in the brain with age (see

‘The ageing brain and nervous system’, p.152) but these correlate poorly with cognitive changes. Broadly, intellectual function is maintained until at least 80 years, but processing is slower. Non-critical impairments include forgetfulness, modestly reduced vocabulary, and slower learning of, eg, languages. These changes are to be expected, their consequences can be managed, and they do not cause significant reduction in functional level.

Three factors support a diagnosis of normal ageing rather than disease:

The ability to maintain function in normal life through aids (eg aidesmemoire: lists or calendars) or adaptations (of one’s environment or of one’s expectations)
Very long time scale of decline: 10-30 years, compared with months or a few years in disease
Relative decline, eg the academic who no longer holds his own at the graduates’ reunion

Impairments in cognitive function without dementia

Age-associated memory impairment (AAMI) or benign senescent forgetfulness

Older people learn new information and recall information more slowly, but given time their performance is unchanged. This is distinct from the impairment in dementia, in that in AAMI, overall function is unimpaired, and usually only less important facts are forgotten. It is often more bothersome to the patient than a concern to relatives (compare dementia, when often the family are much more concerned than the patient).

AAMI can present early (age 40s-50s) when high achievers become frustrated by modest deterioration in speed of new learning. It may be exacerbated by performance anxiety, creating a vicious cycle, and is often helped by psychological strategies to assist memory.

Minimal cognitive impairment(MCI) or cognitive impairment no dementia (CIND)

Impairments are more broad than memory alone, and are felt to be pathological (eg secondary to cerebrovascular disease), but the full criteria for a diagnosis of dementia are not met—eg because there is not yet significant impact on day-to-day functioning.

Progression to dementia occurs in between 5% (community studies) and 10% (memory clinic studies) annually. Thus with time, many patients do develop dementia, but many do not, and in some there is no deterioration.

Diagnosis is important in order to:

Reassure the patient (by distinguishing from dementia)
Modify risk factors for progression
Monitor deterioration such that intervention can begin promptly if progression occurs

Dementia: overview

Dementia is:

An acquired decline in memory and other cognitive function(s)
In an alert (ie non-delirious) person
Sufficiently severe to affect daily life (home, social function)

All three elements must be present in order to make the diagnosis.

Prevalence increases dramatically with age: 1% of 60-65 year olds, > 30% of over 85s. Over 50% of nursing home residents have dementia.

Major dementia syndromes (and proportion of cases in older people) include:

Mixed pathology—(especially Alzheimer’s and vascular) is the commonest type in postmortem studies
Dementia of Alzheimer type (60%)
Vascular dementia (30%)
Other neurodegenerative dementias (15%), eg dementia with Lewy bodies, Parkinson’s disease with dementia, frontotemporal dementia
Reversible dementias (<5%), eg drugs, metabolic, subdural, normal pressure hydrocephalus

Diagnostically, there are many false-positive and false-negative cases. Mild to moderate dementia is easy to miss on a cursory, unstructured assessment. Patients labelled incorrectly as having dementia may be deaf, dysphasic, delirious, depressed, or under the influence of drugs.

HOW TO … Distinguish delirium from dementia

The most common issue in diagnosing the older patient with confusion (‘brain failure’) is whether the patient has delirium alone, dementia alone, or a delirium superimposed on a pre-existing dementia.

Achieve this by combining information from the history with a physical and mental state examination.

▶The history is key. The duration of symptoms is most important.

Information from medical records, carers, and family will help determine whether dementia was present before onset of delirium. ‘When was his memory last as good as yours?’ (Table 9.1)

Table 9.1 Features distinguishing delirium from dementia

Feature	Delirium	Dementia
Mode of onset	Acute or subacute	Chronic or subacute
Reversibility	Often reversible	Rarely reversible
Fluctuation	Diurnal or hour-to-hour fluctuation common	Generally little diurnal variation, although some deteriorate during the evening; ‘sundowning’. Day-to-day fluctuation more common in Lewy Body dementia
Poor attention	Yes (but variable hour-to-hour)	In severe dementia
Conscious level	Usually affected but may be subtle and variable	Normal
Hallucinations and misinterpretations	Common	Usually occurs late in the disease. Visual hallucinations earlier in the disease, especially when symptoms fluctuate, suggests in Lewy Body dementia
Fear, agitation, aggression	Common	Uncommon in early stages
Disorganized thought, unreal ideas	Common	Late. Often poverty of thought
Motor signs	Tremor, myoclonus, asterixis common	Late only
Speech	May be dysarthric, dysnomic	Normal
Dysgraphia	Often present	Usually late
Short and long term memory	Poor	Long-term memory often normal until late

Dementia: assessment

The most important component of assessment. Obtain information from both patient and family/friends. Note onset, speed of progression, symptoms. Take a careful drug history, including over-the-counter drugs and recreational drugs (especially alcohol). Also ask about a family history of early dementia and a personal psychiatric history of, eg, depression.

Usually there is a progressive decline in cognitive function over several years, ending with complete dependency and death (usually due to dehydration, malnutrition, and/or sepsis).

Deterioration may be

Insidious and gradual (eg Alzheimer’s)
Stepwise (suggesting stroke/vascular aetiology)
Abrupt (after a single critical stroke)
Rapid over weeks/months, suggesting a drug, metabolic, or structural cause (eg tumour, subdural)

Abnormalities occur in:

Retention of new information (eg appointments, events, working a new household appliance); short-term memory loss is often severe, with repetitive questioning
Managing complex tasks (eg paying bills, cooking a meal for family)
Language (word-finding difficulty with circumlocution, inability to hold a conversation)
Behaviour (eg irritability, aggression, poor motivation, wandering)
Orientation (eg getting lost in familiar places)
Recognition (failure to recognize first acquaintances, then friends or distant family, then close family, eg spouse)
Ability to self-care (grooming, bathing, dressing, continence/toileting)
Reasoning: poor judgement, irrational or unaccustomed behaviours
Ability to recognize familiar objects, people, and places (agnosia)
Ability to carry out complex, coordinated movements (apraxia)

Physical examination

To determine possible causes of a dementia syndrome, including reversible factors
Look for vascular disease (cardiovascular, peripheral vascular and cerebrovascular), neuropathy, parkinsonism, thyroid disease, malignancy, dehydration, (alcoholic) liver disease
In advanced dementia of any type primitive reflexes (eg grasp, suckling, palmar-mental) and global hyperreflexia with extensor planters may occur

Mental state

Exclude delirium. Features include agitation, restlessness, poor attention and fluctuating conscious level (see Appendix, ‘CAM’, p.692)
Exclude depression. Features include low affect, poor motivation and a negative perspective. Perform a GDS (see Appendix, ‘Geriatric Depression Scale’, p.687)
Measure cognitive function. Serial testing may be helpful in borderline cases—is there evidence of progression? Many measurement tools are available, eg MMSE, Mini-Cog, number of animals named in 1min, clockdrawing test (see ‘Measurement instruments’, p.78, Appendix, ‘The abbreviated mental test score’, p.690, and Appendix, ‘Clockdrawing and the Mini-Cog™’, p.693)

Full neuropsychological assessment (detailed, prolonged assessment by a specialist psychologist) may be helpful in:

Distinguishing between dementia and depression
Distinguishing between different subtypes of dementia
Distinguishing between AAMI and early dementia
Distinguishing between focal impairments (eg aphasic or amnesic syndromes) and dementia
Measuring progression and response to treatment

Disclosure of dementia diagnosis

Each case should be considered individually, but in general the diagnosis should be revealed. Disclosure:

Is consistent with the patient’s right to know (autonomy). Most older people say that they would want to know the diagnosis
Facilitates medical, financial, and care planning, eg advance directives, powers of attorney, living arrangements
Allows for consent to treatment and facilitates participation in research
Facilitates discussion between patient and carer

Arguments against disclosure include a possible depressive reaction, accentuated by a perceived lack of effective treatments. Such a reaction is minimized by sensitive multidisciplinary support that emphasizes the positive therapeutic solutions available.

HOW TO … Investigate a patient with dementia

Cases of reversible dementia are uncommon, but their identification is important, as effective treatment may reverse the impairment and prevent progression. Therefore screen for them.

Blood tests

The following are generally considered useful: FBC, ESR, B₁₂, folate, U,C + E, calcium, LFTs, TSH, CRP, random glucose

Request syphilis and HIV serology only if there are atypical features or special risks.

ECG and CXR

(Evidence of heart disease, occult malignancy.)

Neuroimaging

It is arguable whether every person with dementia should undergo brain imaging. Imaging is indicated where there is:

Early onset (<60 years)
Sudden onset or brisk decline
High risk of structural pathology (eg known cancer, falls with head injury)
Focal CNS signs or symptoms

In more typical cases suggestive of either Alzheimer’s, vascular, or mixed (Alzheimer’s-vascular) dementia, the diagnostic yield is very low. Thus, in most cases, imaging does not alter the clinical management based on history, examination, and lab tests alone. If a patient or carer is particularly anxious (eg fear of brain tumour), imaging may help allay fears, although of course dementia is a far from a benign diagnosis.

CT is the usual imaging modality
MRI identifies posterior circulation vascular pathology with much greater sensitivity
SPECT is used rarely, usually in specialist centres, to more reliably differentiate between Alzheimer’s and vascular dementia

Additional testing as clinically indicated:

EEG is used for suspected frontotemporal dementia or Creutzfeldt-Jakob disease (CJD), or where seizure activity is a possibility
Lumbar puncture where CNS infection is considered

Dementia: common diseases

Alzheimer’s disease (dementia of Alzheimer type)

The most common cause of a dementia syndrome
Diagnosis is made clinically, based on the typical history, mental state examination, and unremarkable physical examination
History—insidious onset, with slow progression over years. Early, profound short-term memory loss progresses to include broad, often global cognitive dysfunction, behavioural change and functional impairment. Behavioural problems are common, usually occurring in moderate to severe dementia, but sometimes preceding overt cognitive impairment
Physical examination—normal
Neuroimaging—demonstrates no other causes of dementia (eg tumour or infarct) and may show disproportionate medial temporal lobe atrophy
Treatment with acetylcholinesterase inhibitors may be indicated (see ‘Dementia: acetylcholinesterase inhibitors’, p.224)
Early-onset Alzheimer’s disease (<65 years) is uncommon, has a stronger genetic component, and is more rapidly progressive

Vascular dementia

The next most common cause
Suggested by vascular risk factors, eg diabetes mellitus, hypertension, smoking or other vascular pathology, with other supporting evidence on history, examination, or tests
History—cognitive impairment may be patchy, compared with the more uniform impairments seen in Alzheimer’s disease. Onset is often associated with stroke, or the deterioration is abrupt or stepwise, however, using ‘multi-infarct dementia’ as a synonym for vascular dementia is imprecise and its use should be discouraged. Frontal lobe, extrapyramidal, pseudobulbar features, and emotional lability are common. Urinary incontinence and falls without other explanation are often early features. Other features may be mostly cortical (mimicking Alzheimer’s disease) or subcortical (eg apathy, depression)
Physical examination often shows:
- Focal neurology suggesting stroke or diffuse cerebrovascular disease (hyperreflexia, extensor plantars, abnormal gait, etc.)
- Other evidence of vascular pathology, eg AF, peripheral vascular disease
Neuroimaging shows either:
- Multiple large vessel infarcts
- A single critical infarct (eg thalamus)
- White matter infarcts or periventricular white matter changes
- Microvascular disease, too fine to be seen on neuroimaging, may cause a significant proportion of vascular dementia, apparent only post-mortem

Differentiating between Alzheimer’s and vascular dementia

The importance of differentiating between Alzheimer’s and vascular dementia can be overemphasized. Their presentations overlap, and pathologies commonly coexist. Increasingly it is believed that much Alzheimer’s disease pathology has a vascular component.

Pragmatically:

In cases where vascular risk factors and/or signs exist, treat vascular risk factors aggressively, whether or not there is significant cerebrovascular pathology on brain imaging
A trial of acetylcholinesterase inhibitors (effective in Alzheimer’s but much weaker evidence in vascular dementia), is probably worthwhile where vascular risk factors and/or pathology exists, but Alzheimer’s may be contributing to the presentation

Dementia and parkinsonism

Dementia with Lewy bodies and Parkinson’s disease with dementia may be considered as extremes of a continuum. In the latter, motor impairments precede cognitive impairments and are more severe. In dementia with Lewy bodies, cognitive and behavioural impairments precede motor phenomena and are more severe. There are frequently additional contributions from Alzheimer’s or vascular pathology. There are believed to be common pathological processes in all these dementia syndromes.

Dementia with Lewy bodies

A gradually progressive background dementia, with insidious onset
Shorter-term fluctuations in cognitive function and alertness
Prominent auditory or visual hallucinations, often with paranoia and delusions
Parkinsonism is commonly present, but often not severe
Typical antipsychotics (eg haloperidol) are very poorly tolerated, leading to worsening confusion or deterioration of parkinsonism. Atypical antipsychotics (eg risperidone, and especially quetiapine) may be better tolerated, but great caution is advised in their use
Levodopa or dopamine agonists may worsen confusion
Anticholinergics (eg rivastigmine) are effective, especially for hallucinations and behavioural disturbance

Note that several features are common to both dementia with Lewy bodies and delirium, eg fluctuations, effect of drugs, perceptual, and psychotic phenomena. When comparing the two, the following is true of dementia with Lewy bodies:

Onset is insidious and progression gradual
No precipitating illness (eg infection) is found
Hallucinations are complex and not the result of misperception of stimuli
Delusions (commonly complex auditory or visual) are well-formed and may be persistent
Syncope frequently occurs
Antipsychotics worsen status (not indicated as a diagnostic trial)

Parkinson’s disease with dementia

People with Parkinson’s disease are much more likely to develop dementia, especially older people, those in the later stages of the disease and those who become confused on Parkinson’s medication
Typical motor features of Parkinson’s disease are present, and may be severe
The presentation and neuropathology is variable, and may resemble Alzheimer’s disease, vascular dementia, or dementia with Lewy bodies
By definition, if features of Parkinson’s precede dementia by more than a year, then the diagnosis is of Parkinson’s disease with dementia, not dementia with Lewy bodies. This applies even if the dementia syndrome is otherwise typical of dementia with Lewy bodies
Multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration also present with both parkinsonism and dementia

Minimal cognitive impairment in Parkinson’s disease

Many patients with PD have subtle impairments of cognition, too mild to justify a diagnosis of dementia. Slowed thinking and deficits in visuospatial, attention and executive function are commonly seen.

Normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) classically presents with the triad:

Gait disturbance (wide-based)
Incontinence of urine
Cognitive impairment (psychomotor slowing, apathy, appear depressed)

▶Most patients with this triad have other (unrelated) causes, or have diffuse cerebrovascular disease.

Assessment

Neuroimaging

Shows ventricles that are enlarged disproportionately compared with the degree of cerebral atrophy
Neuroimaging for unrelated reasons (eg TIA) may reveal ventricular enlargement that appears disproportionate to the degree of cerebral atrophy, suggesting possible NPH. In the absence of clinical features of NPH, the diagnosis cannot be supported, and the patient may be reassured.

Lumbar puncture

Diagnostic and therapeutic procedure
Usually performed if clinical and radiological findings suggestive of NPH
Before the procedure, assess baseline gait (eg timed walk) and cognition (eg MMSE, clock-drawing test)
Opening pressure is normal in NPH
Remove 20-30mL of cerebrospinal fluid (CSF)
Check for improvement in gait and cognition after 1-2hr

Treatment

Ventriculoperitoneal shunting is effective for some, but many do not benefit. Gait is more likely to improve than is cognition.

It is a major procedure, and complications are common, eg infection and subdural haematoma. Decision to proceed requires:

A confident diagnosis (may require specialist neurological review)
Support of patient and carer for the procedure
An assessment that the likelihood of benefit is high

Benefit is more likely in those who:

Have a short history (days or weeks)
Have a known cause—usually trauma or subarachnoid haemorrhage
Have normal brain substance on neuroimaging
Have no significant comorbidities. Cerebrovascular disease is especially relevant
Benefit from lumbar puncture and large volume CSF removal