Secondary Prevention of Dementia: Combining Risk Factors and Scalable Screening Technology

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia. Over a third of dementia cases are estimated to be due to potentially modifiable risk factors, thus offering opportunities for both identification of those most likely to be in early disease as well as secondary prevention. Diabetes, hypertension and chronic kidney failure have all been linked to increased risk for AD and dementia and through their high prevalence are particularly apt targets for initiatives to reduce burden of AD. This can take place through targeted interventions of cardiovascular risk factors (shown to improve cognitive outcomes) or novel disease modifying treatments in people with confirmed AD pathology. The success of this approach to secondary prevention depends on the availability of inexpensive and scalable methods for detecting preclinical and prodromal dementia states. Developments in blood-based biomarkers for Alzheimer's disease are rapidly becoming a viable such method for monitoring large at-risk groups. In addition, digital technologies for remote monitoring of cognitive and behavioral changes can add clinically relevant data to further improve personalisation of prevention strategies. This review sets the scene for this approach to secondary care of dementia through a review of the evidence for cardiovascular risk factors (diabetes, hypertension and chronic kidney disease) as major risk factors for AD. We then summarize the developments in blood-based and cognitive biomarkers that allow the detection of pathological states at the earliest possible stage. We propose that at-risk cohorts should be created based on the interaction between cardiovascular and constitutional risk factors. These cohorts can then be monitored effectively using a combination of blood-based biomarkers and digital technologies. We argue that this strategy allows for both risk factor reduction-based prevention programmes as well as for optimisation of any benefits offered by current and future disease modifying treatment through rapid identification of individuals most likely to benefit from them.

Docking and Molecular Dynamics-Based Identification of Interaction between Various Beta-Amyloid Isoforms and RAGE Receptor

“…At the same time, phosphorylation can reduce the pathogenic effect of the isomerized isoform [ 41 , 42 ]. The Aβ 40 isoform is considered to be more physiological than Aβ 42 , and the Aβ 40 /Aβ 42 ratio is used as one of the AD markers [ 27 ]. Hence, an increase in the level of modified Aβ 42 isoforms in the brain can affect the severity of AD.…”

“…There are Aβ isoforms in the body, which differ in the number of amino acid residues and in their modifications. One of the methods for diagnosing AD is based on the assessment of the ratio of Aβ 40 and Aβ 42 concentrations [ 8 , 9 , 27 ] in blood plasma. According to experimental data, the binding constant values of Aβ 40 and Aβ 42 are close.…”

Neurodegenerative disease of the brain: a survey of interdisciplinary approaches

“…However, a major challenge is in trying to identify this phase before it happens in pre-clinical cognitively healthy people where the amyloid level is often not detectable. Digital technologies allow remote, continuous and affordable monitoring in a participant's own environment, potentially detecting small changes in cognition before clinical symptoms are identified; this may be particularly valuable in people known to be at high risk of dementia [45].…”

Benzo[g]coumarin‐benzothiazole hybrid: A fluorescent probe for the detection of amyloid‐beta aggregates

“…Amyloid‐beta (Aβ) aggregates (called Aβ plaques) caused by unusual accumulation of Aβ40 and Aβ42 in the brain have been considered as the most important biomarker in the pathogenesis of Alzheimer's disease (AD) 1–3 . AD is a neurodegenerative disease and the most common cause of dementia among older adults 4–6 . To date, there has been no perfect cure to reverse or stop the passage and only a few medicines could reduce the AD symptoms 7,8 .…”

“…[1][2][3] AD is a neurodegenerative disease and the most common cause of dementia among older adults. [4][5][6] To date, there has been no perfect cure to reverse or stop the passage and only a few medicines could reduce the AD symptoms. 7,8 In this regard, early diagnosis of AD and the corresponding care are crucial to treat and alleviate the disease.…”