Standardised diagnostic criteria for dementia

Our ageing population has led to an increase in the rates of dementia with an estimated one million people in the UK living with dementia by 2021, and with current costs to the economy of dementia care being around £23 billion a year.¹

The National Dementia Strategy has highlighted the benefits of early, accurate diagnosis of dementia and its subtypes, not just for early access to disease-specific treatments, such as acetyl-cholinesterase inhibitors for Alzheimer’s disease, but also because early diagnosis followed by education, signposting to services and planning, has been shown to significantly improve quality of life for patients and carers thereby delaying residential care, the most expensive aspect of dementia care.²

Despite this, only around 43% of people with dementia have been formally diagnosed, with wide regional variations, leading to an All Party Parliamentary Enquiry group being set up to improve dementia diagnosis rates.³ All primary care and most secondary care clinicians are going to see more people with dementia; hence it is important to have an understanding on how to diagnose dementia and its sub-types.

For most of the diseases causing dementia, definitive diagnosis can only be made by characteristic neuropathological changes on post-mortem examination or brain biopsy. However, there are several standardised clinical diagnostic criteria that have been shown to have good accuracy when compared with post-mortem changes.

Alzheimer’s disease is the most common type of dementia accounting for about 62% of all dementias with mixed (Alzheimer’s and vascular) dementia accounting for a further 10%.⁴ Alzheimer’s disease has an insidious onset and gradual progression with mean survival from diagnosis being 8-10 years.⁵ Typically, there is initial memory impairment accompanied by at least one of aphasia, apraxia, agnosia and disturbance in executive functioning, such that there is a progressive deterioration in the ability to carry out activities of daily living. There may also be behavioural changes including apathy, social withdrawal, agitation and psychotic symptoms. Other causes for cognitive impairment need to be excluded such as delirium, side-effects of medication, depression and intracranial conditions.

The 30-year-old National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria⁶ were well validated with a sensitivity of 81% and specificity of 70% compared to post-mortem changes⁷ and had been widely used in clinical trials and research. These criteria were updated, incorporating recent advances, in 2011 to the National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria⁸ that proposes diagnostic criteria for the three stages of Alzheimer’s disease: the pre-clinical or asymptomatic stage (mainly for research purposes); the prodromal or Mild Cognitive Impairment (MCI) stage; and the clinical or Dementia stage (Box 2).

It is worth noting that the NIA-AA criteria allows diagnosis of Alzheimer’s disease in the dementia stage to be made solely on clinical grounds without needing confirmatory tests like neuroimaging or neuropsychological testing.

It recognises atypical non-amnesic initial presentations such as Posterior Cortical Atrophy (visual variant Alzheimer’s disease)⁹ and it also allows diagnosis of mixed aetiology eg. Alzheimer’s and vascular dementia to be made under possible Alzheimer’s disease dementia.

The NIA-AA criteria allow the diagnosis of Alzheimer’s disease to be made in the prodromal or MCI stage. The clinical criteria for this are:

1.    Concern regarding change in cognition reported by patient, informant or clinician

2.    Objective evidence of impairment in one or more cognitive domains, typically memory

3.    Preservation of independence in functional abilities

4.    Not demented.

Meeting the clinical criteria and positivity for one or more of several biomarkers increases the predictability of MCI converting to the dementia stage. Clinically accessible biomarkers include markers of neuronal injury such as hippocampal atrophy on structural brain imaging; hypometabolism on FDG-PET brain scans and hypoperfusion on HMPAO-SPECT cerebral perfusion scans. Biomarkers currently being researched are markers of brain amyloid deposition such as cerebrospinal fluid amyloid assay and amyloid-labelled PET scans.

Vascular dementia due to significant cerebrovascular disease may account for about 17% of all dementia.¹⁰ The best validated and most widely used diagnostic criteria for Vascular dementia is the National Institute for Neurological Disorders and Stroke with the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN) criteria (Box 3), which requires demonstrating a relationship between the dementia and cerebrovascular disease.¹¹

Post-mortems studies have shown that vascular dementia commonly coexists with Alzheimer’s disease as a mixed dementia.¹¹ Further, vascular risk factors may also be risk factors for Alzheimer’s disease¹² and structural brain imaging changes of white matter ischaemia can also be seen in Alzheimer’s disease.

Dementia with Lewy bodies (DLB) is closely associated with Parkinson’s disease. It is characterised anatomically by the presence of Lewy bodies in post mortem brain histology. Clinically it is characterised by fluctuations in awareness, visual hallucinations and delusions, increased propensity to falls and Parkinsonism (rigidity, tremor, bradykinesia, poverty of expression). The average life expectancy from diagnosis is five to seven years.

There are three clinical phenotypes that  have been described: Parkinson’s disease (if the Lewy body pathology is predominantly in the subcortical structures); Parkinson’s disease dementia and dementia with Lewy bodies (where the Lewy body pathology is also seen in the cerebral cortex). The latter two can be distinguished by the timing of the onset of dementia. If the dementia occurs within a year of onset of motor symptoms the diagnosis is dementia with Lewy bodies, if it is after a year the diagnosis is Parkinson’s disease dementia. Dementia is very common in patients with Parkinson’s disease with up to 75% of individuals developing it during the course of the disease.¹³

The best validated diagnostic criteria for dementia with Lewy bodies is the Third DLB Consortium Consensus Criteria.¹⁴

Although Fronto-temporal dementia (FTD) accounts for only 2% of all dementias it is the second most common cause of dementia (after Alzheimer’s disease) in patients under 65 years, with the average age of onset being 54 years.¹⁵ There may be a positive family history and the prognosis is variable, with life expectancy from diagnosis ranging from two to 10 years. There are three recognised phenotypes:

• Behavioural variant Fronto-temporal dementia (previously known as Pick’s disease):  characterised by early personality and behavioural changes, loss of insight, disinhibition and lack of social awareness. These features usually predate memory impairment. Disturbance of mood, speech and continence often occur
• Progressive non-fluent aphasia: patients present with impaired fluency of speech due to articulation difficulty, phonation of speech and syntactic errors. Speech comprehension is preserved
• Semantic dementia: patients remain fluent with normal phonology and syntax but increasing difficulty with comprehension, especially single-word comprehension.

The clinical diagnostic criteria for behavioural variant Fronto-temporal dementia¹⁶ from 1998 were updated in September 2011 by the International Consensus Criteria and shown to have good sensitivity.¹⁷

It is important to diagnose dementia early and to differentiate its sub-types because the treatment options and prognosis for these diseases vary.¹⁷ As summarised in the text, most of the current, well-validated and widely used diagnostic criteria rely mainly on the clinical features, with diagnosis being supported by neuroimaging and neuropsychological testing. It is therefore important for all clinicians to have an understanding of these criteria in order to improve the diagnostic rates and to also be wary of diagnosis solely based on brain imaging and neuropsychological testing without clinical co-relation. Diagnostic criteria for the rarer sub-types of dementia are beyond the scope of this paper.

Conflict of interest: none declared

References

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17.          Rascovsky K, Hodges JR, Knopman D, et al., Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia, Brain 2011; 134(Pt 9): 2456-77