Lewy Body and Frontotemporal Dementia

Introduction

This article covers two dementia subtypes that are less common than Alzheimer's or vascular dementia but disproportionately important to recognise correctly, because misdiagnosis carries specific risks (dangerous drug reactions in Lewy body dementia) or because the presentation is easily mistaken for a different condition entirely (frontotemporal dementia mistaken for primary psychiatric illness). For general dementia assessment, see ¹.

Both are also under-diagnosed. DLB is thought to account for a substantially larger share of dementia than it is diagnosed as, with many cases labelled as Alzheimer's disease because the fluctuation and hallucinations are not specifically asked about. FTD is frequently missed for years while patients are managed by psychiatry for a presumed personality disorder, late-onset psychiatric illness, or a mid-life crisis. In both cases the diagnostic delay has real consequences - unnecessary antipsychotic exposure in DLB, and lost time for financial and family planning in FTD.

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the third commonest dementia subtype, caused by abnormal intracellular aggregates of alpha-synuclein (Lewy bodies) in the cerebral cortex and brainstem - the same underlying pathological process as Parkinson's disease, reflecting a shared 'Lewy body spectrum' of disorders.²

Core diagnostic features

• Fluctuating cognition, with pronounced variation in attention and alertness - sometimes hour to hour, more marked than the fluctuation seen in other dementias
• Recurrent, detailed visual hallucinations, typically well-formed (people, animals) and often not distressing to the patient, at least initially
• Spontaneous parkinsonism: bradykinesia, rigidity and/or rest tremor, arising in the context of the cognitive syndrome rather than induced by antipsychotic medication
• REM sleep behaviour disorder: acting out dreams during REM sleep - vocalising, punching, kicking - often preceding the cognitive syndrome by years and a strong supportive feature when present

Supportive features include severe antipsychotic sensitivity (see below), postural instability and falls, autonomic dysfunction (postural hypotension, constipation, urinary symptoms), and depression.

Neuroleptic sensitivity - the critical safety point

Investigations

• Standard dementia screening bloods and structural imaging as for dementia generally (see ¹)
• DaTscan (dopamine transporter SPECT imaging) - shows reduced striatal dopamine transporter uptake in DLB and Parkinson's disease, helping distinguish DLB from Alzheimer's disease where the clinical picture is unclear
• MIBG cardiac scintigraphy - reduced cardiac uptake supports Lewy body pathology, used in specialist practice
• Polysomnography - can confirm REM sleep without atonia, objectively establishing REM sleep behaviour disorder where the history is uncertain
• MRI - typically shows relatively preserved medial temporal lobe volume compared with Alzheimer's disease, which can be a useful discriminating feature

Autonomic and sleep features

Autonomic dysfunction is prominent in DLB and is a significant, treatable source of morbidity that is easily attributed to other causes. Postural hypotension causes falls and syncope, and is frequently worsened by the very drugs used to treat parkinsonism; constipation is near-universal and can itself precipitate delirium; urinary urgency and incontinence are common; and excessive daytime sleepiness compounds the fluctuating cognition. Recognising these as part of the disease, rather than as separate incidental problems, allows them to be managed proactively - checking lying and standing blood pressure at review, maintaining a bowel regimen, and reviewing contributory medication.

Management

• Cholinesterase inhibitors (donepezil, rivastigmine) have reasonable evidence in DLB, often more effective for both cognitive symptoms and hallucinations than in other dementia subtypes, and are generally used first-line
• Parkinsonism is treated cautiously with levodopa if significantly disabling, balancing motor benefit against the risk of worsening hallucinations or confusion
• Avoid antipsychotics as above; where hallucinations are non-distressing, reassurance and monitoring alone may be appropriate rather than pharmacological treatment
• Manage autonomic symptoms (postural hypotension, constipation) proactively, since they contribute significantly to falls and quality of life
• Falls assessment, given the combination of parkinsonism, cognitive fluctuation and autonomic instability - see ³

Frontotemporal dementia

Frontotemporal dementia (FTD) is a group of conditions caused by progressive atrophy of the frontal and/or temporal lobes, typically presenting at a younger age than other dementias (commonly 45-65), making it an important cause of young-onset dementia. Unlike Alzheimer's, memory is often relatively preserved early, while personality, behaviour or language are affected first.⁴

Behavioural variant FTD

The commonest presentation, driven by frontal lobe involvement, characterised by early, prominent changes in personality and social conduct rather than memory:

• Disinhibition: socially inappropriate behaviour, impulsivity, loss of usual social tact
• Apathy: loss of motivation and initiative, often mistaken for depression
• Loss of empathy and interpersonal warmth, sometimes distressing for family who describe the person as 'not themselves' in personality terms
• Perseverative, stereotyped or ritualistic behaviour
• Hyperorality and dietary change: altered food preferences, overeating, or putting inedible objects in the mouth
• Executive dysfunction, often out of proportion to relatively preserved memory and visuospatial skills early on

Primary progressive aphasia

The language-led presentation of FTD, itself divided into two main variants:

Investigations

• Standard dementia screening bloods, as for dementia generally
• MRI brain: characteristic frontal and/or temporal lobe atrophy, often asymmetric, in contrast to the medial temporal predominance of Alzheimer's
• Neuropsychological assessment, showing a disproportionate executive/behavioural or language deficit relative to memory
• A minority of cases are genetically driven (e.g. MAPT, GRN, C9orf72 mutations), relevant where there is a strong family history, and genetic counselling may be appropriate

Management

There is no licensed disease-specific cognitive drug for FTD, and cholinesterase inhibitors and memantine are generally not effective and are not recommended, unlike in Alzheimer's disease - a frequently examined negative point.

• Behavioural management is the mainstay: structured routine, environmental modification, and managing specific behaviours (disinhibition, dietary change) with practical strategies
• SSRIs are sometimes used for behavioural symptoms (disinhibition, repetitive behaviours, dietary change), with modest evidence of benefit
• Speech and language therapy for primary progressive aphasia, including communication strategies and, where relevant, augmentative communication aids
• Carer support is especially important in FTD, given the younger age of onset (with implications for work, finances and dependent children) and the particular distress caused by personality change in a previously well-known family member
• Capacity and legal/financial planning should be addressed early, since executive dysfunction and impaired insight can affect decision-making capacity earlier and more unpredictably than in Alzheimer's

Managing behavioural symptoms without antipsychotics

Because antipsychotics are hazardous in DLB and of limited benefit in FTD, both conditions force a reliance on non-pharmacological management of distress and behavioural disturbance - which is, in any case, first-line in all dementias. A structured approach identifies what the behaviour is communicating rather than treating it as a symptom to be suppressed.

1. Describe the behaviour precisely - what happens, when, where, who is present, and what happens immediately before and after it
2. Exclude a physical cause: pain, constipation, urinary retention, infection, hunger, thirst, or a medication side effect are extremely common triggers and are often the whole explanation
3. Exclude an environmental trigger: noise, overstimulation, unfamiliar surroundings, a change of carer, poor lighting causing misperception
4. Consider unmet psychological need: boredom, loneliness, fear, loss of autonomy, or a need for meaningful occupation
5. Modify what can be modified - routine, environment, communication approach, activity - and review whether the behaviour changes
6. Only then consider medication, at the lowest effective dose, for the shortest time, with a planned review date

Comparing the subtypes

Red flags

Prognosis

Both conditions are progressive, without disease-modifying treatment currently available. DLB carries additional risk from falls, autonomic instability and the specific danger of neuroleptic exposure, which can precipitate a sudden, severe decline if mismanaged. FTD, given its younger age of onset, has a particularly significant impact on families, employment and dependants, making early, proactive planning and support especially important alongside symptomatic management.

DLB generally progresses somewhat faster than Alzheimer's disease, with median survival from diagnosis typically shorter, driven partly by the added burden of falls, aspiration from parkinsonian swallowing difficulty, and autonomic instability. FTD survival varies considerably by variant, with the behavioural variant generally progressing faster than the primary progressive aphasias; where FTD coexists with motor neurone disease - a recognised overlap, particularly with C9orf72 mutations - the prognosis is substantially worse and is determined largely by the motor neurone disease.