Alzheimer's disease

Currently most patients with Alzheimer's disease are seen in old age psychiatry clinics. Episodic memory deficit is usually the earliest and most prominent symptom, with behavioural and psychological symptoms of dementia (BPSD) more common in the later stages. Routine neurological examination is usually unremarkable: myoclonus and Parkinsonism may be seen (Box 4 gives a glossary of neurological terms used in this article), usually late in the disease course. In early-onset Alzheimer's disease, arbitrarily defined as onset at ≤65 years of age, such as those cases arising from mutations in the presenilin-1 gene, various neurological signs may be found, including myoclonus, Parkinsonism and, rarely, spastic paraparesis and cerebellar ataxia (Larner Reference Jozefowicz2013a). Variant forms of Alzheimer's disease may also have prominent neurological symptoms, such as the visual complaints in posterior cortical atrophy and language deficits in logopenic progressive aphasia (Dubois Reference Dubois, Feldman and Jacova2014), and more usually present directly to ophthalmologists and neurologists respectively.

Simple tests of limb praxis, the translation of an idea into action, may be of use in diagnosis of Alzheimer's disease. These include pantomiming learned actions, such as brushing the hair or striking and blowing out a match, or copying meaningless hand gestures or postures. Limb apraxia is relatively common at presentation in all the Alzheimer's disease variants (Ahmed Reference Ahmed, Baker and Thompson2016).

Frontotemporal dementia

Patients with the behavioural variant of frontotemporal dementia (bvFTD) are often, and understandably, referred for psychiatric assessment in the first instance. Neuropsychiatric manifestations include apathy, disinhibition, loss of insight, transgression of social norms, emotional blunting, and repetitive and stereotyped behaviours. Psychiatrists generally recognise that these symptoms do not fit any disorder recognised in the psychiatric classification. Of the linguistic variants of frontotemporal dementia – non-fluent (agrammatic variant of primary progressive aphasia) and fluent (semantic variant of primary progressive aphasia) – behavioural symptoms may be more prominent in the latter, because of the failure of comprehension. Non-fluent cases may sometimes be erroneously labelled as Alzheimer's disease or vascular dementia (Randall Reference Randall and Larner2020).

Neurological examination is usually unremarkable. Mild akinesia and Parkinsonian gait or posture may occur. Limb apraxia is less common than in Alzheimer's disease, with the possible exception of non-fluent progressive aphasia (Ahmed Reference Ahmed, Baker and Thompson2016), and the cumulative probability of myoclonus is lower than in Alzheimer's disease or dementia with Lewy bodies (Beagle Reference Beagle, Darwish and Ranasinghe2017). Motor sequencing deficits may be found with frontal pathology, as shown with the Luria three-step test: a repeated series of hand movements (fist, edge, palm) is shown to the patient, who is then asked to reproduce them. Environmental dependency behaviours such as imitation behaviour and utilisation behaviour may occur or be provoked in people with bvFTD (Ghosh Reference Ghadiri-Sani and Larner2013). Imitation behaviour is the unbidden reproduction by the patient of gestures (echopraxia) or utterances (echolalia) made by the examiner in the patient's presence. Utilisation behaviour, in which seeing an object implies that it should be used, may be tested by handing the patient a cup or a pair of glasses without comment or instruction, and seeing whether the items are appropriately used.

Psychotic symptoms (delusions, hallucinations) are generally rare in frontotemporal dementia, with the possible exception of that with concurrent motor neuron disease (FTD+MND). In one series of patients with FTD+MND, over two-thirds were under the care of a psychiatrist at the time of neurological diagnosis, some with provisional diagnoses of hypomania or depression, and all were receiving either antidepressant or antipsychotic medications (Sathasivam Reference Sanders and Keshavan2008). FTD+MND sometimes manifests an early psychotic phase characterised by hallucinations and delusions, which may be dramatic and bizarre (Larner Reference Larner2013b; Ziso Reference Zeman2014) but is often transient. FTD+MND is often genetic, a consequence of hexanucleotide repeat expansions in C9orf72, which may also present as obsessive–compulsive disorder or bipolar disorder. Examination of the motor system may be useful here, sometimes disclosing focal wasting and weakness, with muscle fasciculation, particularly in the shoulder girdle musculature; indeed, such signs may alert clinicians to the need for revision of pre-existing psychiatric diagnoses (Ziso Reference Zeman2014). A combination of upper and lower motor neuron signs, particularly in the same muscle (e.g. biceps spasticity and brisk reflex in a fasciculating and weak muscle), is highly suspicious for concurrent MND.

Vascular dementia

Vascular dementia or cognitive impairment has multiple types (Skrobot Reference Sathasivam, Doran and Larner2017). That consequent on large vessel infarction may be attended with obvious focal neurological signs, such as spastic hemiparesis with hemiparetic gait, aphasia or visual field defect, dependent on the affected arterial territory. Hemisensory dysfunction may also be a feature. More likely to be encountered in psychiatric practice is vascular cognitive impairment due to small vessel ischaemic disease, in which behavioural features such as emotional lability may be prominent, along with a subcortical pattern of cognitive deficits typified by slow information processing, apathy and difficulty sustaining attention. A gait disorder characterised by short steps and a broad base but with relative preservation of upright stance (compare with Parkinson's disease, where stooped posture is common), and sometimes termed marche à petit pas, may be seen in subcortical ischaemic vascular cognitive dementia or impairment. Limb rigidity of Parkinsonian type, often more evident in the lower limbs, may also occur (Staekenborg Reference Skrobot, O'Brien and Black2008).

It should of course be remembered that concurrence of vascular and Alzheimer type pathology, mixed dementia, is relatively common in older people, and that vascular changes on brain imaging do not automatically equate to vascular dementia or vascular cognitive impairment (although they increase the risk of later dementia and mandate the treatment of vascular risk factors). The presence of such neuroimaging appearances in people with functional cognitive symptoms may also be a particular issue, leading to incorrect initial diagnoses or undermining patient confidence in the diagnosis of functional disorder. The key, as ever, is to base the diagnosis on the patient's symptoms, not neuroimaging in isolation.

Dementia with Lewy bodies

Visual hallucinations are one of the core diagnostic criteria of dementia with Lewy bodies (DLB) (McKeith Reference Madan2017), often taking the form of complex images of people or animals. Insight that these are not real is often preserved (hence they are sometimes referred to as ‘pseudo-hallucinations’) and there is often a lack of associated distress, two features that may help to distinguish these visual hallucinations from those occurring in psychiatric disorders. A sensation of a presence, someone standing beside the patient (anwesenheit), is another symptom that may prompt psychiatric referral, although visual hallucinations are atypical for psychiatric disorders and auditory hallucinations are not a recognised feature of DLB. Diagnostic clues may include the pattern of cognitive decline, which is fluctuating and with attention and visuospatial function affected more than memory and orientation. Parkinsonian motor features may be subtle or absent in the early stages of disease. There is reported to be a higher cumulative probability of developing myoclonus in DLB than in Alzheimer's disease (Beagle Reference Beagle, Darwish and Ranasinghe2017). Enquiries for a prior history of rapid eye movement (REM) sleep behaviour disorder (‘dream enactment’) or of anosmia may also be of value in reaching a diagnosis of DLB.

Prion diseases

Psychiatric features are relatively frequent in sporadic Creutzfeldt–Jakob disease (sCJD), the most common of the human prion diseases, but these are not adequately encompassed within current diagnostic criteria (Ali Reference Ali, Barborie and Larner2013). Sporadic CJD can sometimes have a long ‘psychiatric’ prodrome with features suggestive of depression, and one of the rare molecular subtypes of sCJD (VV1) can present with prominent psychiatric features in young people. Visual hallucinations may sometimes occur in sCJD, usually elemental forms (colours, shapes) in contrast to the formed visual hallucinations of DLB (Du Plessis Reference Du Plessis and Larner2008). Psychiatric features are also common in the early stages of variant CJD, including dysphoria, social withdrawal and anxiety. Limb myoclonus may be an early clue to the diagnosis of sCJD, but other neurological signs may also occur, including cerebellar ataxia, pyramidal (spasticity, hyperreflexia) and extrapyramidal (akinesia, rigidity) signs (Nakatani Reference Morris and Grattan-Smith2016).

Functional neurological disorder – cognitive subtype

Cognitive symptoms of functional origin are commonly encountered in clinics dedicated to cognitive disorders, prompting the development of diagnostic criteria akin to other functional neurological disorders (Ball Reference Ball, McWhirter and Ballard2020). The ‘attended alone’ sign may be suggestive of this diagnosis (Bharambe Reference Bharambe and Larner2018), likewise the provision of a written list of symptoms, la maladie du petit papier (Randall Reference Ojagbemi, Emsley and Gureje2018), both signs indicative of the inconsistencies between self-reported symptoms and everyday function which typify functional disorders (Ball Reference Ball, McWhirter and Ballard2020). A detailed description of episodes of forgetting is also indicative of internal inconsistency, and contrasts with the inability of individuals with amnesia to give any such account (Bailey Reference Bailey, Poole and Blackburn2018). Limb praxis may be preserved in patients diagnosed with subjective cognitive impairment (Ahmed Reference Ahmed, Baker and Thompson2016).

Parkinson's disease and other Parkinsonian syndromes

Although patients with the typical motor features of Parkinson's disease (akinesia, rigidity, rest tremor, stooped posture) are unlikely to present initially to psychiatrists, the emergence of visual hallucinations, either spontaneous or with dopaminergic therapies, suggestive of the development of cortical Lewy body disease, may prompt psychiatry referral, as might progression of Parkinson's disease to cognitive impairment and dementia.

The applause sign, clapping more than three times in imitation of the examiner's demonstration of three claps, was first described in progressive supranuclear palsy (PSP) and later in other disorders, such Alzheimer's disease and frontotemporal dementia, although less frequently than in PSP and DLB (Isella Reference Ghosh, Dutt and Bhargava2013). The applause sign is a motor perseveration, probably indicative of frontal lobe dysfunction.

Huntington's disease

The behavioural features of Huntington's disease, including irritability, apathy, depression and schizophrenia-like features, along with subcortical-type cognitive decline, may prompt initial psychiatric referral. Observation of chorea may suggest the diagnosis, although these movements can be subtle.