# Frontotemporal dementia
## Frontotemporal Dementia

Dementia is an umbrella term given to a clinically recognised multifaceted syndrome characterised by progressive deterioration of cognitive, motor, behavioural and psychological functions, that impacts significantly upon quality of life and the capacity of the individual to remain independent and self-sufficient (McKeith & Cummings 2005); it is formally defined as an impairment of memory function and one other cognitive domain by the Diagnostic and Statistical Manual of Mental Disorders (cited in McKeith & Cummings 2005).
Prior to the age of 70 years, prevalence and incidence has been found to remain relatively low (Cutler et al 2010), after which they begin to increase up until the age of 90 to 95 years (Jorm 2002; Cutler et al 2010). This rise is hypothesised to continue a similar trend beyond this age as medical advances extend life expectancy (Jorm, Dear & Burgess 2005). The most recent incidence and prevalence prediction of dementia in 2010 estimated that approximately 257,000 people, or 1.2%, of the Australian population experiences some form of dementia (Cutler et al 2010); this is staggered across 3 main age periods, consisting of an incidence rate of 3.5% and 3.3% in 70-74 year-old males and females respectively, 21.1% and 24.4% prevalence in the 85-89 age group, and 37.2% and 47.4% in the 95 years and above cluster (Cutler et al 2010). Subject to the source of estimated population growth employed, it has been predicted that dementia incidence in Australia will rise to a figure ranging from 588,000 to 982,000 cases by 2050, an increase of more than 241% (Cutler et al 2010; Jorm, Dear, & Burgess 2005). Prevalence has been projected to rise at a significantly greater rate within the elderly age group in comparison to prevalence in the overall Australian population, reflecting the sub-group’s anticipated fast growth rate and a concurrent rise in prevalence rates (Jorm, Dear & Burgess 2005). However, due to the limited availability of Australian prevalence studies, predictions primarily draw upon international studies and meta analyses, which do not accurately reflect the unique Australian population dynamics that exist, which inadvertently influence dementia rates, primarily the consideration of the indigenous population and immigration trends (Jorm, Dear & Burgess 2005; Henderson & Jorm 1998, cited in Australian Institute of Health & Welfare [AIHW] 2006). By comparison, approximately 35.6 million people were estimated to suffer from dementia worldwide in 2010, with approximately 4.6 million new cases diagnosed each year, and incidences predicted to double every 20 years until 2040 on a global scale (Draper 2010; Ferri et al 2005). Wancata and colleagues (2003) estimated that there will be more than 1 million cases of dementia by 2050 in various western European countries, with an overall increase of 45%.
However, while statistical data provides a strong representation of the overall situation, the prevalence of the various dementia sub-types must also be considered due to the unique challenges that each present in relation to nursing care and integration into society (Edberg & Edfors 2008). These issues significantly impact upon the current health system and are likely to in the future unless effective preventive strategies, and ultimately a curative treatment, can be implemented (Ferri et al 2005). One such variant is frontotemporal dementia, also known as frontal lobe dementia, which is broadly characterised by detrimental changes in language, personality and social behaviour. It is the fourth most common form of dementia in Australia and United States, accounting for 5% and 5-8% of cases respectively (Cutler 2010; Salzbrenner et al 2009; Mendez 2011). The incidence of this dementia is further compounded by its tendency to occur within the 45 – 65 age group and is considered the second most common cause of young-onset dementia in the population after Alzheimer’s Disease (Piguet et al 2011; Johnson et al 2005), while appearing to remain a relatively rare occurrence above the age of 79 (Neary, Snowden & Mann 2005). The drop in prevalence with age has been theorised to be partly due to older adults not obtaining the degree of investigation needed to establish a positive frontotemporal dementia diagnosis or post-mortem analysis, and a lowered life expectancy due to earlier onset (Piguet et al 2011; Johnson et al 2005). Despite a relatively small prevalence of frontotemporal dementia, these percentages specifically represent one of a trio of syndromes that are collectively united by the physical location in which the degenerative changes first begin to occur.
The pathophysiology of frontotemporal dementia is primarily restricted to the frontal and temporal lobes during the initial and intermediate stages, a trait that has been found to be unique to the disease through various investigation methods. The frontal lobe is chiefly responsible for executive functions of motor tasks and regulating behaviour through inhibition of inappropriate actions with respect to social cues, which includes adjustment of emotional responses such as empathy (Marra et al 2007; Hodges et al 1999). Concurrently, the temporal lobe enables the use of language and semantic memory (Marra et al 2007; Hodges et al 1999). Neuropathological examinations across various studies have demonstrated significant atrophy in varying frontal lobe regions, including the medial, anterior and fronto-orbital sections, along with atrophy of the prefrontal and anterior temporal cortex, and basal ganglia (Starkein et al 1994; Marra et al 2007; Neary, Snowden & Mann 2005). Several additional studies (cited in Piguet 2011) have demonstrated atrophy infiltrating subcortical regions such as the hippocampus, caudate, striatum, putamen, amygdala, thalamus, and hypothalamus, with Barnes and colleagues (cited in Piguet 2011) establishing amygdala atrophy as an efficient differentiating factor between behavioural-variant frontotemporal dementia and Alzheimer’s disease. These disease-related atrophic changes may be significantly more aggressive, reaching an annual overall atrophy rate of up to 8% in comparison to the 0.3% p.a. rate noted in healthy controls (Piguet et al 2011). Hypoperfusion of the aforementioned lobes is another notable feature observed in studies, together a strikingly normal perfusion rate in the parietal and occipital lobes when compared to the control group (Neary et al; Miller et al, both cited in Starkein et al 1994). This pattern of perfusion deficit has been noted in other dementia subtypes presenting with challenging behaviour and poor social cue recognition (Kumar et al, cited in Starkein et al 1994). Several unique histological changes correlating with atrophic changes have been noted, including micro-vacuolation secondary to loss of neuronal cells and the presence of Pick’s bodies, which are tau protein deposits that infiltrate and enlarge neuronal cell bodies (Neary, Snowden & Mann 2005; Lund &Manchester groups, cited in Neary, Snowden & Mann 2005). The presence of abnormal tau proteins has suggested a genetic predisposition in some diagnoses due to known genetic mutations in the tau protein gene, and is associated with the rare form of familial frontotemporal dementia; however histological findings cannot differentiate frontotemporal dementia from the other variants of frontal lobe degeneration (Neary, Snowden & Mann 2005).
The earliest indications of frontal lobe changes are often expressed through gradual personality changes, with family members noting more frequent inappropriate remarks or less acceptable responses to social interactions, often with no appreciation of the nature or consequence of their reactions (Moretti et al 2005). Sufferers may also begin to find it increasingly challenging to organise and plan daily activities, struggle to apply reasoning to abstracts concepts and remain focused on activities or demonstrate flexibility to react and solve problems as they arise in the environment (Moretti et al 2005; Neary, Snowden & Mann 2005). Disease progression is marked by an increasing reduction in core emotions, like sadness, and deterioration of social cue recognition that allows them to infer the thoughts and emotions of others, with several studies noting progressively impaired ability to recognise facial and vocal emotions (cited in Neary, Snowden & Mann 2005). Snowden and colleagues (2001) noted that as personalities continue to change, sufferers become increasingly socially disinhibited, fatuous and overactive, or develop emotional blunting, apathy and become inactive. Towards the middle stages of the disease, frontal lobe functions are impaired to such a degree that stereotyped behaviour patterns begin to appear. Multiple studies have noted these to include motor mannerisms, development of complex mandatory routines, and eating habit alterations, with the development of gluttony, a preference for sweet food, and indiscriminate eating (cited in Neary, Snowden & Mann 2005). Language deterioration also marks significant levels of cortical decline with the development of speech stereotypy and declining self-expression capacity; concurrently, advancing frontal and temporal lobe deterioration produces echolalia and mutism in the later stages (Neary, Snowden & Mann 2005).
A decreased pain response, as a consequence of motivational and emotional dampening, hypersensitivity to neutral stimuli, and an overall alteration of sensory stimuli responses are another subset of features that have been ascribed to frontotemporal dementia, although the low sensitivity in studies prevents inclusion among features typically attributed to frontotemporal dementia (Snowden et al 2001). Initially there are no physical signs, however with disease progression, the development of incontinence, akinetic-rigid syndrome and tremor, and emergence of primitive reflexes become increasingly common (Neary, Snowden & Mann 2005). Interestingly, spatial skills remain markedly well preserved, and as such frontotemporal dementia sufferers are able to navigate the environment, localise and manipulate objects, and retain memory and basic visual perception capacity (Neary, Snowden & Mann 2005).
As with a lot of neuro-degenerative diseases, the collection of signs and symptoms expressed in the early stages of frontotemporal dementia lack definitive presentation patterns, requiring multimodal approaches and expert clinicians to obtain a precise diagnosis (Marra et al 2007). Furthermore, distinguishing frontotemporal dementia from other dementias and frontotemporal lobe degeneration subtypes, whilst taking into account individual variations within the disease itself, is often challenging in the early stages (AIHW 2006). Consequently, screening of individuals who stand to benefit from more intensive assessment is generally done by a general practitioner on detection of cues via routine examinations or based on concerns reported by carers (Bridges-Webb & Wolk 2003, cited in AIHW 2006). Further investigations involve neuroimaging techniques, neuropsychological profiling and cognitive testing, done with the intention of excluding alternative causes of reversible dementia-like symptoms, and culminating with frontotemporal dementia as a final differential diagnosis (AIHW 2006; Marra et al 2007). Structural MRI may demonstrate cortical atrophy associated with frontotemporal dementia, while the visual rating scale developed by Kipps and colleagues can quantify these atrophic changes (2007, cited in Piguet et al 2011). Early hypoperfusion and hypometabolic changes have been reliably detected by functional neuroimaging techniques that employ single-photon emission computed tomography (SPECT) and Fluorodeoxyglucose(FDG)-PET (Piguet et al 2011); these changes occur earlier than cortical atrophy, allowing for earlier diagnosis. Signs and symptoms also play part in diagnosis from a neuropsychological aspect, and are assessed through performance in tests designed to target certain functional areas of the cortex. Frontotemporal dementia tends to perform poorly in executive function tests, failing to adhere to established rules, remain focused upon the task, have a tendency to lack concreteness of thought and respond impulsively when answering (Neary et al 1988, Snowden et al 1996, all cited in Neary, Snowden & Mann 2005). These deficits also compromise performance in tasks designed to test other cognitive domains such as memory, where decreased attention span and difficulty engaging high-level thought processes impair recall, while poor organisation skills affect the ability to reproduce figures in drawing tests (Neary, Snowden & Mann 2005). Conversely, unremarkable results have been consistently found in visuoconstructional and spatial tests, which are significantly different to the result patterns presented by Alzheimer’s disease and other dementia forms (Medez et al 1996, cited in Neary, Snowden & Mann 2005). In regards to quantifying test results, Marra and colleagues (2007) and others (Thompson et al 2005 & Pachana et al 1996, cited in Neary, Snowden & Mann 2005) have suggested that qualitative approaches to behavioural and neuropsychological disturbances present greater benefit for differential diagnosis, as reliance on test scores alone may mask qualitative differences. Currently there is insufficient evidence to determine ideal monitoring frequency and mode, however it is practical for carers to remain observant and as with any other progressive disease, consistent medical reviews are required as signs and symptoms change (Buntix et al 2011). Progression and emergence of signs and symptoms should prompt reviews of the environment, nutrition and medications to ensure these remain appropriate (Cotter 2007). Early diagnosis presents significant benefits for families and carers, as well as the subject themselves as it allows planning of future care, accommodation, treatment and support to commence. It also provides the person with the opportunity to establish legal representatives who respect and instigate their wishes when they are no longer able to make sound decisions (AIHW 2006).
Correct diagnosis is essential for appropriate management of incurable diseases such as frontotemporal dementia; however lack of imaging technology limited the distinction of frontotemporal dementia from other subtypes and hence appropriate treatment and management strategies. In the mid 1970s, Sylh and colleagues (1976) discussed the ‘Homes for Special Care’ program that was implemented to manage high numbers of long-stay mental disorder patients in hospitals requiring nursing or residential care but unlikely to benefit from further inpatient treatment, particularly those lacking social support to remain in the community. This program, set up in Ontario and replicated in a similar manner in Australia, functioned as minimalist-style care facilities where the staff often lacked training required to manage and address issues unique to the population; a mixture of chronic or terminal illnesses and mental disorders, with no recognition of individual needs of each subgroup (Sylh et al 1976). Residents received a narrower band of treatment options in comparison to other facilities and were often denied treatments such as psychotherapy, ECT, industrial and occupational therapy which were the mainstream treatment options for mental disorders. During this period, pharmacology was advocated to allow for easier behaviour management, and in these hospices medications were rarely adjusted since initial prescription yet were routinely supplied (Sylh et al 1976). In essence these places were designed to simply house those with frontotemporal dementia and provide basic nursing care, without application of strategies that are recommended in current literature. By comparison, recent literature promotes the use of medications to facilitate daily function by aiding better executive planning in the early to moderate stages of the disease, and to manage behaviour that poses a risk to either the patient themselves or to carers, but prescribed only with informed consent (AIHW 2006). Psychosocial interventions are habitually used in conjunction with pharmacology and involve comprehensive evaluation to locate possible behaviour triggers and subsequent environment modification (Curtin 2010). Implementation of strategies such as music and reminiscence therapies has been shown to have positive impacts (Hulme et al 2009). Current living environments, private or institutional, aim to maximise quality of life and functional status through the support of trained staff and by providing support to carers, emphasising individual-specific care (Curtin 2010); all literature stresses the importance of continual access to social interaction and supportive environments, regardless of disease progression (Hulme et al 2009).
The incurable aspect of frontotemporal dementia means that prevention must be a focal part of healthy ageing strategies. The most recent literature review suggests that promoting intellectual endeavours, physical activity and remaining socially active may aid in prevention but establish that these are not solid prevention strategies (Savica & Pettersen 2011). Links to specific predisposing factors have been suggested to include use of anticholinergic drugs, hypertension, type II diabetes and its associated precursors, poor cardiovascular health, and poor diet, suggesting that environmental and lifestyle modification may play a significant part in preventing frontotemporal dementia (Jessen et al 2010; Staessen et al 2011; Luchsinger 2010; Thoenen et al 2005; Cutler et al 2010). Other promising fields include lithium, used in the treatment of bipolar disorder, which may prevent tau protein progression although the biochemical mechanism is unknown (Thoenen et al 2005). As the age of onset for frontotemporal dementia is often earlier than other dementia subtypes, prevention strategies must be promoted to middle age adults well before retirement age in order to deter detrimental changes, particularly as cortical changes may be present for up to 20 – 30 years prior to symptom onset (Harman 2006, cited in Millard, Kennedy & Baune 2011).
Overall, the small prevalence frontotemporal dementia makes it a minority among the dementia variants, however its clinical manifestations present novel challenges for clinicians due to its early age of onset and individual variations. While diagnosis is reasonably clear-cut, management strategies are not definitive in practice and at present, prevention must be a key aspect of 21st century health promotion for the older Australian.