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Changing mood pin: apathy rather than depression is the early warning for vascular dementia

The number of people living with dementia worldwide is foreseen to triple by 2050, making early diagnosis and intervention increasingly important. Late-life cognitive functioning may be maintained by targeting modifiable factors such as cardiovascular risk, physical activity and diet. Hypertension, especially if lately diagnosed and poorly handled, seems to play a a particular predisposing role. Apathy, defined as a reduction in ‘goal-directed behaviour’, is a common neuropsychiatric symptom in SVD, and is distinct from depression, which is another symptom in SVD. Although there is some symptomatic overlap between the two, previous MRI research linked apathy, but not depression, with white matter network damage in SVD. Apathy offers an important early warning sign of dementia in individuals with cerebrovascular disease, but depression does not, new research led by the University of Cambridge suggests.  Depression is often thought to be a risk factor for dementia but this may be because some depression scales used by clinicians and researchers partially assess apathy.

The study, published in the Journal of Neurology, Neurosurgery & Psychiatry, is the first to examine the relationships between apathy, depression and dementia in individuals with cerebral small vessel disease (SVD). SVD may occur in one out of three elderly individuals, causes about a quarter of all strokes, and is the most common cause of vascular dementia.  The team studied two independent cohorts of SVD patients, one from the UK and the other from the Netherlands. Across both cohorts, they found that individuals with higher baseline apathy, as well as those with increasing apathy over time, had a greater risk of dementia. In contrast, neither baseline depression nor change in depression had any detectable influence on dementia risk. Over 450 participants – all with MRI-confirmed SVD – recruited from three hospitals in South London and Radboud University’s Neurology Department in the Netherlands, were assessed for apathy, depression and dementia over several years. In the UK cohort, nearly 20% of participants developed dementia, while 11% in the Netherlands cohort did, likely due to the more severe burden of SVD in the UK cohort.

In both datasets, patients who later developed dementia showed higher apathy, but similar levels of depression at baseline, compared to patients who did not. These findings were consistent despite variation in the severity of participants’ symptoms, suggesting that they could be generalised across a broad spectrum of SVD cases. The relationship between apathy and dementia remained after controlling for other well-established risk factors for dementia including age, education, and cognition. Recent MRI work suggests that similar white matter networks underlie motivation and cognitive function in SVD. Cerebrovascular disease, which can be caused by hypertension and diabetes, can lead to network damage, resulting in an early form of dementia, presenting with apathy and cognitive deficits. Over time, SVD-related pathology increases, which is paralleled by increasing cognitive and motivational impairment, eventually becoming severe enough to meet criteria for a dementia state. The study provides the basis for further research, including the mechanisms that link apathy, vascular cognitive impairment and dementia.

Dr. Jonathan Tay, Lead Author, from Cambridge’s Department of Clinical Neurosciences, explained: “There has been a lot of conflicting research on the association between late-life depression and dementia. Our study suggests that may partially be due to common clinical depression scales not distinguishing between depression and apathy. This implies that apathy is not a risk factor for dementia per sè, but rather an early symptom of white matter network damage. Understanding these relationships better could have major implications for the diagnosis and treatment of patients in the future. Continued monitoring of apathy may be used to assess changes in dementia risk and inform diagnosis. Individuals identified as having high apathy, or increasing apathy over time, could be sent for more detailed clinical examinations, or be recommended for treatment”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemsitry.

Scientific references

Tay J et al. J Neurol Neurosurg Psychiatry 2020 Jul 10.

Amin Al Olama A et al. Neurology 2020; 94(12):1294-1302.

Tay J et al. Neurology 2019 Mar 12; 92(11):1157-1167. 

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it