Elsevier

Cortex

Volume 73, December 2015, Pages 36-61
Cortex

Review
Behavioural and psychological symptoms of dementia in Down syndrome: Early indicators of clinical Alzheimer's disease?

https://doi.org/10.1016/j.cortex.2015.07.032Get rights and content

Abstract

Behavioural and Psychological Symptoms of Dementia (BPSD) are a core symptom of dementia and are associated with suffering, earlier institutionalization and accelerated cognitive decline for patients and increased caregiver burden. Despite the extremely high risk for Down syndrome (DS) individuals to develop dementia due to Alzheimer's disease (AD), BPSD have not been comprehensively assessed in the DS population. Due to the great variety of DS cohorts, diagnostic methodologies, sub-optimal scales, covariates and outcome measures, it is questionable whether BPSD have always been accurately assessed. However, accurate recognition of BPSD may increase awareness and understanding of these behavioural aberrations, thus enabling adaptive caregiving and, importantly, allowing for therapeutic interventions. Particular BPSD can be observed (long) before the clinical dementia diagnosis and could therefore serve as early indicators of those at risk, and provide a new, non-invasive way to monitor, or at least give an indication of, the complex progression to dementia in DS. Therefore, this review summarizes and evaluates the rather limited knowledge on BPSD in DS and highlights its importance and potential for daily clinical practice.

Section snippets

Introduction: Down syndrome (DS) and Alzheimer's disease (AD) – a disruptive marriage

Intellectual disability, previously referred to as mental retardation, is defined as ‘a significantly reduced ability to understand new or complex information and to learn and apply new skills’ (World Health Organization, 2014) and reaches a prevalence of approximately 1% in the Western population (Maulik, Mascarenhas, Mathers, Dua, & Saxena, 2011). The most common genetic cause of human intellectual disability is DS, caused by the triplication of the human chromosome 21 (HSA21). DS, or trisomy

BPSD

BPSD, or in a narrower sense also known as neuropsychiatric symptoms (NPS), are defined as ‘a heterogeneous range of psychological reactions, psychiatric symptoms and behaviours resulting from the presence of dementia’ (Finkel, 2001, Lyketsos et al., 2011). Even though BPSD have been intensively studied during the last two decades, they are far from being a newly recognized entity. Already in 1906, Alois Alzheimer described hallucinations, delusions, paranoia and agitation in his famous 51-year

Diagnosis of BPSD in DS: a challenging endeavour

Whereas the dementia field largely uses the terminology of BPSD or NPS to address behavioural and psychological changes, reports on demented DS subjects referred to them in numerous ways: from behavioural disturbances (Prasher & Filer, 1995), behavioural changes (Adams et al., 2008, Duggan et al., 1996), behavioural deficits and excesses (Adams and Oliver, 2010, Adams et al., 2008, Millichap et al., 2003) to psychiatric symptoms (Moss and Patel, 1995, Urv et al., 2010), maladaptive behaviour (

Cross-sectional approaches

The first paper to report on BPSD in a series of demented DS individuals was published by Dalton and Crapper-McLachlan (1986). They summarized a total of 35 reported cases that were described between 1946 and 1985. Neuropathological confirmation of AD was available in 33 cases. Clinical dementia was present in 25 individuals. Common reported features were personality changes and apathy/inactivity (Table 2), while depression, disorientation and hallucinations/delusions were less prevalent.

Behavioural and psychological phenotypes in DS

Since Langdon Down's ‘Observations on an Ethnic Classification of Idiots’ (1866) and Mitchell's notes on sixty-two cases of ‘kalmuc idiots’ (1876), clinicians and researchers have tried to describe and define a typical behavioural phenotype of DS (Collacott et al., 1998, Down, 1995, Fraser and Mitchell, 1876). Is there indeed a characteristic behavioural phenotype of DS, and if so, which recurrent symptoms are generally present? Such pre-morbid symptoms are particularly relevant to take into

Clinical implications and future perspectives

BPSD are associated with increased suffering, accelerated cognitive decline, earlier institutionalization and an increased mortality risk for patients, increased caregiver burden and higher costs (Finkel, 2000). In that context, accurate and early recognition of BPSD in DS may increase awareness and expand our understanding of the behavioural aberrations, thus enabling adaptive caregiving and, importantly, allowing for therapeutic interventions.

However, assessment of BPSD in DS is currently

Neurobiology of BPSD in DS

Unravelling the underlying neurobiological mechanisms of BPSD in DS would contribute to the general understanding of these burdensome behavioural and psychological changes and aid the development of targeted therapeutic, and possibly preventive, interventions. An increasing number of studies addressed the mechanisms of BPSD in AD, for instance pointing at specific dysregulated monoaminergic neurotransmitter systems (Vermeiren et al., 2014a, Vermeiren et al., 2014b). In agreement, we recently

Conclusion

In conclusion, BPSD are a core symptom of dementia in addition to cognitive decline and impaired activities of daily living, and are extensively studied in MCI and AD patients in the general population. Despite the extremely high risk to develop AD and the lack of early (bio)markers with limited invasiveness to predict the onset of AD in DS, most dementia research in the DS population did not comprehensively assess BPSD. The great variety of cohorts, diagnostic methodologies, covariates and

Conflict of interest

The authors herein declare no conflict of interest.

Acknowledgements

This work was supported by the Alzheimer Research Center of the University Medical Center Groningen (UMCG), a subsidy from the Gratama-Stichting/Stichting Groninger Universiteitsfonds (2015-04), the Interuniversity Poles of Attraction (IAP Network P7/16) of the Belgian Federal Science Policy Office, a Methusalem excellence grant of the Flemish Government, agreement between Institute Born-Bunge and University of Antwerp, the Medical Research Foundation Antwerp, the Thomas Riellaerts research

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