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Biomarkers and Alzheimer’s Disease: What Will the Future Bring for ‘The Worried Well’?

Published online by Cambridge University Press:  04 June 2021

Luis Fornazzari*
Affiliation:
Department of Neurology, Memory Disorder Clinic, St Michael’s Hospital, University of Toronto, Toronto, Canada
Corinne E. Fischer
Affiliation:
Department of Psychiatry, St Michael’s Hospital, University of Toronto, Toronto, Canada
*
Correspondence to: Luis Fornazzari, Department of Neurology, Memory Disorder Clinic, St Michael’s Hospital, University of Toronto, Toronto, Canada. Email: [email protected]
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Abstract

Type
Editorial
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

The field of dementia research and clinical practice is paved with good intentions and Subjective Cognitive Impairment (SCI) or more colloquially the ‘worried well’ (WW-SCI) is one of them. Its consistency resists the passage of time and the different fashions affecting the practice and research of Modern Medicine.

The term worried well has elements that may overlap with psychiatric disorders. There, the common day to day human experience of worrying becomes excessive and uncontrollable, and there are constant verbal thoughts of impending disaster. The ‘worried well’ in the dementia field, on the contrary, is characterized by a preoccupation with concern about progressive deterioration of their cognitive functions on their day to day activities. Worries in general according to some authorities correspond to a cognitive phenomenon intimately associated to affective, physiological, and to the inter-intrapersonal behavioral processReference Borkovec, Ray and Stuber1 and its pathophysiology corresponds to a deficit in the attention control, a constituent of the working memory.Reference Nazanin and Eysenck2

The ‘worried well’ usually refer themselves to Memory Clinics for further assessment. The history of the ‘worried well’ is rather recent in the field of dementia. Its definitions fluctuates regarding its nature, from a psychiatric perspective in cases of depressionReference Cooney, Joorman, Eugene, Dennis and Gotieb3 to a minor cognitive deficit focusing on impairments in attention, language, and memory.Reference Nasiri, Mashiadi, Bigodeli and Ghama Nabad4 Regardless of these definitions and conceptualizations, the WW-SCI has been an important and challenging group of patients in research and in the day to day clinical evaluation of cognitive impairment, as it is often impossible to distinguish patients who are cognitively normal from those who will ultimately progress to cognitive impairment.

The prevention and evaluation of dementia is also relatively new in the clinical neuroscience field. Evaluation of the WW-SCI is done through clinical assessment, neuropsychological testing, functional and behavioral evaluation, and in particular repeated clinical follow-ups.Reference Mitchell5 These patients are an important group to study and should always be included in the early diagnosis of cognitive impairment, as reported in the notable paper in this issue of the Canadian Journal of Neurological Sciences by Sutherland et al. from the Rural and Remote Memory clinic from the University of SaskatchewanReference Sutherland, Kirk, Karunanayake, O’Connell and Morgan6 with the gradual but sustained appearance of biomarkers, we see positive rewarding days, not only for the ‘worried well’ but for all the disciplines associated with cognitive disorders, particularly those with neurodegenerative conditions. They started with the first imaging biomarkers in the 1980s, allowing us to visualize the structural brain damage with MRI (1992) and detection of in vivo of brain deposits of abnormal proteins including AB PET(2004) and Tau PET (2013). This was then followed by more invasive CSF markers like AB protein, tau, phosphorylated tau, and neuro filament light, followed by the critically needed blood-based biomarkers. These have been used in the research field only since 2017, with AB42/AB40, serum Nfl, tau 181, ptau 217, and the most recent, plasma detection of p-tau231, perhaps the easiest accessible biomarker of the most incipient disease pathology.Reference Ashton, Pascoal and Karikari7 Another exciting development is the use of the latest mouth swab test where calculating polygenic risk score offers a simple and effective way to select mildly cognitively impaired individuals who are most likely to decline cognitively over the next 4 years.Reference Daunt, Ballard and Creese8

As per other markers in the daily clinical practice, such as blood sugar in diabetes mellitus, blood pressure for hypertension, these new serum markers could detect abnormal brain deposits years before the first clinical manifestations characteristic of Alzheimer’s disease. This would help memory clinics to further characterize this important group of Worried Well-Subjective Memory Impairment individuals to discover if the worries are the product of a healthy aging process or an emerging neurodegenerative disorder that is in progress, affording an opportunity for prevention and early treatment.

Disclosures

The authors have no conflicts of interest to declare.

References

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