Prevalence of EOD

Epidemiological findings about the prevalence of EOD are scarce and inconsistent (Moore and Buss, Reference Moore and Buss2004; McMurtray et al., Reference McMurtray, Clark, Christine and Mendez2006; Mercy et al., Reference Mercy, Hodges, Dawson, Barker and Brayne2008). Among the general population, the prevalence of EOD was found to range between 67 and 81 cases per 100,000 in those aged 45 to 65 years (Treves et al., Reference Treves1986; Hoffman et al., Reference Hoffman1991; Ratnavalli et al., Reference Ratnavalli, Brayne, Dawson and Hodges2002; Harvey et al., Reference Harvey, Skelton-Robinson and Rosser2003). Among patients with dementia, the prevalence rates of those experiencing EOD was found to range from 7% up to nearly 30% (Yokota et al., Reference Yokota2005; McMurtray et al., Reference McMurtray, Clark, Christine and Mendez2006; Shinagawa et al., Reference Shinagawa2007). These discrepancies may be partially explained by differences in the methodological approaches used in the different studies, such as whether the study was based on a retrospective review of patients' records (McMurtray et al., Reference McMurtray, Clark, Christine and Mendez2006) or on the assessment of a consecutive sample attending a memory clinic (Shinagawa et al., Reference Shinagawa2007).

Causes of EOD

Many diseases and conditions have been identified as causes of EOD, such as Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), cerebral vasculitis, Parkinson's disease, Huntington's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis (ALS), traumatic brain injury, HIV, chronic alcoholism, chronic drug abuse, and brain tumors (Gomez-Tortosa et al., Reference Gomez-Tortosa, Ingraham, Irizarry and Hyman1998; Nyenhuis and Gorelick, Reference Nyenhuis and Gorelick1998; Greicius et al., Reference Greicius, Geschwind and Miller2002; Sampson et al., Reference Sampson, Warren and Rossor2004; Yokota et al., Reference Yokota2005; Alzheimer's Association, 2006; Knopman et al., Reference Knopman, Petersen, Cha, Edland and Rocca2006; McMurtray et al., Reference McMurtray, Clark, Christine and Mendez2006; Mendez, Reference Mendez2006).

AD has been described as the most common dementia diagnosis even among young adults (Williams et al., Reference Williams, Dearden and Cameron2001; Harvey et al., Reference Harvey, Skelton-Robinson and Rosser2003; Yokota et al., Reference Yokota2005), followed by VaD (Fujihara et al., Reference Fujihara, Brucki, Rocha, Carvalho and Picccolo2004; McMurtray et al., Reference McMurtray, Clark, Christine and Mendez2006). Early onset Alzheimer's disease was found to be associated mainly with mutations in three genes: presenilin 1 (PSEN1, chromosome 14); presenilin 2 (PSEN2, chromosome 1); and amyloid precursor protein (APP, chromosome 21) (Filley et al., Reference Filley2007; Raman et al., Reference Raman, Lin, Suri, Hewitt, Contanitnescu and Phillips2007). However, these genes accounted for less than 0.1% of all early onset cases, pointing to the need for more research on the combination of genetic and environmental causes (Whalley, Reference Whalley2001).

Symptoms of EOD

The symptoms of EOD are diverse and include behavioral, cognitive, neurological and psychiatric symptoms (Sampson et al., Reference Sampson, Warren and Rossor2004). It should be noted that there are no specific symptoms or integration of symptoms that can be considered as absolute symptoms of the disease. In addition, some symptoms may emerge at the early stages of the disease, while others do not (Haase, Reference Haase2005).

Despite these differences, several common symptoms have been identified. These include memory loss, particularly loss of short-term memory, depression and anxiety. In a study conducted among caregivers of persons with EOD in Ireland, it was found that 56% of the persons with EOD experienced depression and 71% suffered from anxiety. Other symptoms include delusions and hallucinations, difficulties in finding the right words, and difficulties with concentration (Haase, Reference Haase2005). For example, in a study that examined 185 persons with EOD in the U.K., the most prevalent symptoms were non-cognitive and behavioral symptoms, with 53% of the participants experiencing delusions, 44% hallucinations, and 61% aggressive behavior (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998).

Diagnosis of EOD

EOD is a frequently misdiagnosed condition (Mendez, Reference Mendez2006), with 30–50% of cases reported as mistaken or uncertain diagnoses (Bentham and Fontaine, Reference Bentham and Fontaine2005). There are several reasons for these difficulties. First, the diagnoses of EOD are more diverse than the diagnoses of LOD. Second, in the case of AD, EOD may present salient cognitive deficits apart from loss of memory and convulsive paraparesis, spasms or myoclonus. Third, EOD frequently appears together with neuropsychiatric characteristics that are out of proportion to cognitive deficits (Mendez, Reference Mendez2006).

Diagnosis is especially problematic among persons who have a history of functional psychiatric disorder. Moreover, cultural and linguistic influences on test implementation may make analysis difficult when working with persons from ethnic minority groups (Bentham and Fontaine, Reference Bentham and Fontaine2005).

Since precise diagnosis is essential to management as well as to the patients' and family caregivers' planning, several steps have been recommended for securing an accurate diagnosis in the majority of EOD disorders. These steps include obtaining a clinical history, including the history of dementia, estimating the risk factors for dementia, carrying out a neurological examination, and employing MRI and other tests as needed (Sampson et al., Reference Sampson, Warren and Rossor2004; Mendez, Reference Mendez2006). In order to assist clinicians in the assessment and diagnosis of EOD, the use of clinical positron emission tomography (PET) has recently been recognized as an efficient method for the diagnosis of early onset AD (McMurtray et al., Reference McMurtray, Licht, Yeo, Krisztal, Saul and Mendez2008).

The clinical difficulties encountered in the diagnosis of EOD are intensified by the time that elapses between the appearance of the first signs of dementia and the diagnosis, which typically exceeds that of LOD. This might be attributable to the inability of younger persons and their family members even to consider the possibility of dementia at a young age, resulting in a delay in seeking help. Additionally, since dementia is generally age-related, primary care physicians might be less inclined to consider a diagnosis of dementia in young patients. Indeed, a study of 61 cases of EOD in Ireland showed that in only 10 cases were the consulting general practitioners able to make a definitive diagnosis (Haase, Reference Haase2005). The most common misdiagnoses were depression, stress, burnout and menopausal changes (Harris and Keady, Reference Harris and Keady2004; Haase, Reference Haase2005).

Given the diagnosis difficulties of primary care physicians, the majority of patients with suspicious EOD are referred to specialists. A study of 132 persons with dementia under the age of 65 conducted in the U.K. showed that 37% were referred to a psychiatrist, 28% to a neurologist, 11% to a psychogeriatrician, and 11% to a liaison psychiatrist (Williams et al., Reference Williams, Dearden and Cameron2001).

Treatment of EOD

Relatively little research has focused on the treatment of EOD (Sampson et al., Reference Sampson, Warren and Rossor2004; Bentham and Fontaine, Reference Bentham and Fontaine2005). Although there are few specific therapies available for the majority of the disorders of EOD, the treatment of EOD can be divided into pharmacological and non-pharmacological interventions. Pharmacological treatment includes donepezil, galantamine, rivastigmine and memantine (Bentham and Fontaine, Reference Bentham and Fontaine2005). Non-pharmacological interventions include a variety of treatments, such as environmental modification, occupational therapy and speech therapy (Sampson et al., Reference Sampson, Warren and Rossor2004).

Differences between EOD versus LOD of the AD type

As previously noted, AD is the most common type of dementia associated with EOD (Koedam et al., Reference Koedam2008). Therefore, some research attention has been devoted to examining the differences between early onset and late onset AD. Early studies reported considerable clinical differences between both types of dementia. Compared to persons with late onset AD, persons with early onset AD were found to have more focal cortical deficits, such as visuospatial and language impairments, and fewer memory impairments (Loring and Largen, Reference Loring and Largen1985; Mayeux et al., Reference Mayeux, Stern and Spanton1985; Filley et al., Reference Filley, Kelly and Heaton1986). More recent studies, however, show that these differences are mainly age related and not unique to early or late onset (Licht et al., Reference Licht, McMurtray, Saul and Mendez2007).

Costs of care for people with EOD

Although limited attention has been devoted to the costs of care for people with EOD, findings show that the overall cost of dementia care for younger persons is almost equal to the cost for older adults with the disease and may be even higher. In a study examining the cost of care for younger adults with dementia in the U.K., it was found that the direct cost for a single person during one year was £7,868. Most of the expenses were related to institutional care (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998). However, since the study did not examine indirect costs, such as morbidity and mortality, it can be assumed that the actual costs would be even higher.

In addition, younger persons with EOD and their families endure a double economic strain because they often lose their income while at the same time not being eligible for financial assistance. EOD is not categorized as a disability or a terminal illness and therefore does not qualify younger patients to receive the same benefits as those available to older persons (Haase, Reference Haase2005).

Psychological and social challenges faced by individuals with EOD

The onset of dementia is always accompanied by serious psychological and emotional difficulties for the persons afflicted with the disease, as well as their families. These difficulties are increased in the case of patients younger than 65 years old. First, they experience a loss of independence as the result of not being able to perform everyday tasks. Second, this loss of independence leads to a change in their relationships with partners and other family members. For example, in many cases the onset of the disease and its progress is accompanied by a reversal in roles, with children becoming the caregivers of their own parents, even at a relatively young age (Haase, Reference Haase2005). Third, when EOD results in the loss of employment, the consequences often extend beyond the loss of family income and may have a devastating impact on the individual's self-esteem and sense of efficacy and self-worth (Alzheimer's Association, 2006).

Caregiving in EOD

Several studies have examined the influence of EOD on the informal caregivers of young adults with dementia (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998; Luscombe et al., Reference Luscombe, Brodaty and Freeth1998; Freyne et al., Reference Freyne, Kidd, Coen and Lawlor1999; Moore and Buss, Reference Moore and Buss2004; Kaiser and Panegyres, Reference Kaiser and Panegyres2007). The majority (82%) of patients with EOD were found to have an informal caregiver providing the assistance needed (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998). Regarding the characteristics of informal caregivers, it was found that they tended to be relatively young, in their 50s (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998; Freyne et al., Reference Freyne, Kidd, Coen and Lawlor1999), male as well as female (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998; Williams et al., Reference Williams, Dearden and Cameron2001).

Similar to family members caring for elderly persons with AD, caregivers of persons with EOD reported it to be a difficult task, associated with physical and emotional burdens. For example, a study comparing caregivers of persons with EOD and LOD found that the caregivers of persons with EOD reported higher levels of burden than the caregivers of those with LOD (Freyne et al., Reference Freyne, Kidd, Coen and Lawlor1999). Another study found that the majority (66%) of caregivers of persons with EOD perceived their emotional well-being as poor or very poor (Williams et al., Reference Williams, Dearden and Cameron2001). These high levels of stress among caregivers of persons with EOD might stem from the long duration of caregiving and the lack of formal and informal support (Arai et al., Reference Arai, Matsumoto, Ikeda and Arai2007). An additional explanation for the high strain reported by caregivers of persons with EOD relates to their young age, which might find them inadequately prepared for the role of caregiving (Arai et al., Reference Arai, Matsumoto, Ikeda and Arai2007).

Anxiety and depression disorders were also found to be common consequences of caring for persons with EOD. In a study examining the frequency of anxiety disorders among caregivers of persons with EOD, as many as 60% reported feeling anxious, with higher rates observed among female caregivers (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998). Depression was also found to be very prevalent among caregivers of persons with EOD, especially among spouses (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998; Kaiser and Panegyres, Reference Kaiser and Panegyres2007). In addition to the stress associated with caregiving in LOD, EOD is also associated with strains related to the unique characteristics of presenile dementia, including financial insecurity, high stigmatization, and negative effects on marital quality.

EOD typically affects persons who are still actively employed and productive and who may serve as the providers for their families. Consequently, the impact that a diagnosis of EOD has on the family's financial security might be more severe than in the case of LOD. Moreover, those afflicted with EOD might still be parents of relatively young children or may have dependent parents who are still alive. Additionally, since persons with EOD are still relatively young and mostly married (Haase, Reference Haase2005), the effect that the disease has on their marital quality might be detrimental (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998). Finally, since EOD is not as common as LOD, caregivers might feel excluded and socially isolated, particularly if there is a lack of appropriate services available (Freyne et al., Reference Freyne, Kidd, Coen and Lawlor1999, Kaiser and Panegyres, Reference Kaiser and Panegyres2007).

A final note should be added regarding the unique anxiety and burden associated with the development of the disease by first-degree at-risk relatives of persons with EOD. As previously stated, several genes have been identified as responsible for autosomal dominant early-onset familial AD (Filley et al., Reference Filley2007). Predictive genetic testing is clinically available for mutations in these genes in at-risk adults. Although the goal of genetic testing is to identify at-risk individuals early and start effective treatments in symptomatic persons and strategies for delaying the onset of the disease in presymptomatic ones, several negative arguments are associated with the use of genetic testing presymptomatically and as a diagnostic tool (Schutte, Reference Schutte2006). These include psychological consequences such as anxiety and depression. To minimize these negative consequences it is advised to provide specific information and knowledge to family members about genetic testing and to develop psychosocial support services specially geared to their needs (Schutte, Reference Schutte2006).

Services for persons with EOD

Existing services for people with EOD include community/home support, day care, residential and nursing care. Although the number of support groups for caregivers and individuals with EOD is growing progressively, these services are still relatively scarce and their availability is not always recognized. For example, a study conducted in Ireland among 61 persons with EOD showed that less than two-fifths of the participants utilized any of these services. The lack of special services for younger people with dementia may also be attributed to the fact that professional staff in general psychiatric services frequently lack adequate knowledge and training to recognize and treat these disorders. At the same time, elder care services (such as day care and assisted living facilities) are inappropriate for younger persons with dementia.

Studies of home care services are very scant in comparison to those of long-term residential care services (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998; Moore and Buss, Reference Moore and Buss2004). In a study conducted in the U.K., it was found that 30% of 185 patients with EOD did not live in their own homes. Consequently, it was predicted that five residential care facilities and 10 nursing homes or long-stay hospital beds would be required for persons with EOD among the 100,000 people at risk for developing dementia (Harvey et al., Reference Harvey, Rossor, Skelton-Robinson and Garralda1998).