Alzheimer’s disease is the most common type of dementia. In patients aged 65 years or older, who have some kind of cognitive decline, it accounts for over 50% of cases. Progression to full dementia may take several years following the signs of mild cognitive impairment (MCI) at the early stage of AD [Linn, 1995; Petersen, 1999]. The pathological mechanism of AD and associated dementia is proposed in Figure 1.

The criteria for the clinical diagnosis of AD is shown in Table 2. Diagnosis of AD is aided by neuroimaging studies (see Assessment and diagnosis); however, definitive diagnosis can only be confirmed using histopathological evidence of amyloid plaques and neurofibrillary tangles from biopsy or autopsy [Mirra, 1991, Perl, 2000].

Rare genetic mutations can cause early-onset autosomal dominant familial AD, whereby mutations in the presenilin genes (presenilin I and II) and the amyloid precursor protein (APP) gene affect the APP and its metabolism. The amyloid cascade hypothesis suggests that accumulation of beta-amyloid, by overproduction or failure to break down APP, leads to amyloid deposition resulting in amyloid plaques, neurofibrillary tangles and cell death [Plassmam, 2000].

Apolipoprotein E (ApoE) – a protein involved in lipid and cholesterol transport – has been identified as a genetic determinant of susceptibility to late-onset AD, although it is not causative in disease onset. There are three common alleles for the ApoE gene: e2, e3 and e4. The e4 allele confers an increased risk of AD, whereas the e2 allele may be protective [Poirier, 1993].

Vascular dementia is the second most common cause of dementia. It results from vascular or circulatory lesions or from diseases of the cerebral vasculature leading to ischaemia or infarction.

Clinical features supporting the diagnosis of vascular dementia are shown in the Hachinski Ischaemic Score (see Table 3). Items are weighted according to their importance and should not be part-scored. A score of 7 or more is considered to be suggestive of vascular dementia.

The NINDS–AIREN criteria for the clinical diagnosis of vascular dementia [Roman, 1993] are shown in Table 4.

Evidence suggests that vascular dementia can co-exist with AD leading to diagnostic confusion and mixed forms of dementia. Vascular lesions may also contribute to the severity of AD [Snowdon, 1997]. The presenting clinical features in Table 3 show that differentiating AD from vascular dementia can be clinically difficult. Neuroimaging studies showing cerebrovascular disease – infarcts or deep white matter ischaemia – support the diagnosis of vascular dementia (see Neuroimaging).

Dementia with Lewy bodies (DLB) is an increasingly recognized cause of dementia in elderly patients. The typical presenting features of DLB include fluctuating dementia with prominent deficits in attention, frontal executive tasks and visuospatial abilities. The cognitive profile of DLB contains both cortical and subcortical features (see Table 5).

The characteristics of cortical and subcortical dementias are shown in Table 5.

Fronto-temporal dementia (FTD) – sometimes called Pick’s complex – is characterized by focal frontal atrophy with personality and behavioural disturbances, or temporal atrophy with either progressive aphasia or semantic dementia [Hodges, 1992; Neary, 1998]. Onset of FTD is observed in a younger age group than other dementias and diagnosis may be difficult in the early stages of disease.

Routine neuropsychological assessment procedures such as the Mini-Mental State Examination (MMSE) are usually insensitive at detecting frontal abnormalities, therefore more extensive neuropsychological testing is required to establish frontal deficit in patients suspected with FTD. The clock drawing test may be helpful.

Pathological causes for FTD include Pick’s disease – characterized by large ballooned neuronal cells, called Pick’s bodies, fronto-temporal dementia lacking distinct histopathology [Knopman, 1990]; and FTD with parkinsonism, associated with abnormal tau protein and chromosome 17 mutation [Knopman, 1990]. Approximately 20% of FTD cases are familial, demonstrating an autosomal dominant pattern of inheritance [Cummings, 1992].

More than 100 types of dementias have been documented and reviewed [Perry, 1990; Cummings, 1992; Pryse-Phillips W; Morris, 1994]. Apart from the four main types discussed above, other less common dementias result from:

A number of potentially reversible causes of dementia include thyroid deficiency or excess, vitamin B₁₂ deficiency, abnormal calcium levels and intracranial space-occupying lesions.