Image: Scene from the ADRC's Clinicopathological Correlation Conference
Read these snapshots of current research at the UW Alzheimer's Disease Research Center, spanning findings in neurology, precision medicine, genetic risk, and vascular brain health.
Neurology
Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration. A. Staffaroni et al. Alzheimer Disorders & Associated Disorders, July 2019 // Kimiko Domoto-Reilly, Christina Caso, Walter Kukull
Researchers recently made an important advance in characterizing a person’s risk of familial dementia, a dementia syndrome directly linked to a specific marker in a person’s genetic makeup, before symptoms arise. This research will help scientists identify those at risk early on, and help patients achieve the best possible outcomes by kickstarting interventions at the appropriate time point.
The study genetically tested 268 family members with a family history of frontotemporal lobar dementia (FTLD) and put subjects into categories based on whether or not they carried a pathogenic gene change. The researchers then used subjects’ brain atrophy patterns and severity to develop a model that categorizes an individual into asymptomatic or demented cognitive status. The scientists found that their model was 90% accurate at categorizing mutation-carrying subjects, so they tested their model on a different group of subjects, to see if it could predict whether or not other mutation carriers without significant cognitive symptoms would later progress to dementia. Researchers created dementia risk scores based on degree of atrophy for the asymptomatic or questionably symptomatic participants, and they found that the score predicted the risk for whether or not the subject would go on to develop dementia over the next 5 years.
The UW ADRC has previously demonstrated that there is a wide range of timing of symptom onset within FTLD families. This research shows that individualized brain atrophy patterns may have strong potential for predicting timing of dementia onset, and that such techniques could be useful in guiding treatment for neurodegenerative disease.
Precision Medicine Approaches
Associations Between Depression, Traumatic Brain Injury, and Cognitively-Defined Late-Onset Alzheimer’s Disease Subgroups. J. Bauman et al. Molecular Psychiatry, May 2019 // Shubhabrata Mukherjee, Emily Trittschuh, Mackenzie Moore, Susan McCurry, Wayne McCormick, Eric B. Larson, Paul K. Crane
ADRC researchers have been working for years to study the nuance in clinical presentations of Alzheimer’s disease-type dementia and define biological subtypes.
In previous work, ADRC researchers classified 4,050 Alzheimer’s cases, from several major prospective cohort studies in the country, into specific groups based on their most prominent type of cognitive symptoms at the time of diagnosis (including memory, executive functioning, language, and visuospatial functioning). The study also found a particularly strong relationship between a particular variant of the APOE gene and risk for the memory loss subgroup. The APOE e4 allele is a strong risk factor for developing late-onset Alzheimer’s for people with European ancestry.
For this study, the team investigated the occurrence of depressive symptoms and history of traumatic brain injury among these subtypes. They found that people with the memory subtype were less likely to report depression and restless sleep. The study found no differences in traumatic brain injury history across subtype groupings.
The discovery of these differences in risk for depression and restless sleep among these cognitive subtypes, along with their previous genetic findings, support the team’s hypothesis that subgroups of clinical Alzheimer’s disease have a biological basis. The group is now interested to further investigate the implications of restless sleep for dementia symptoms.
Resilience and Risk
Resistance and resilience to Alzheimer’s disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort. C. Latimer et al. Acta Neuropathologica Communications, June 2019 // Caitlin S. Latimer, Nicole F. Liachko, Mitchell D. Kilgore, Laura E. Gibbons, Jonathan Henriksen, Martin Darvas, Kimiko Domoto-Reilly, Suman Jayadev, Thomas J. Grabowski, Paul K. Crane, Eric B. Larson, Brian Kraemer, Thomas Bird, C. Dirk Keene
‘Resilience’ is the term for a person who had a high level of Alzheimer’s pathology in the brain, yet who stayed cognitively intact until death; while ‘resistance’ is a person who never develops any pathologic brain change. Previous UW ADRC research has shown that people were less likely to have been resilient during life if their brain tissue showed additional pathologies on top of the Alzheimer’s disease hallmarks of amyloid and tau. These included vascular injury and Lewy bodies. This research study, which used autopsy brain tissue resources from the Adult Changes in Thought study, focused on a pathology that can appear in aging brains called TDP-43. They found that people who had been resilient or resistant to Alzheimer’s disease pathology did not also show accumulations of TDP-43; yet almost all of the brains from age-matched people affected by symptoms of dementia during life did have TDP-43 pathology. This finding leads the team to suggest that TDP-43 undermines brain resilience and increases one’s risk of developing dementia later in life, and it provides impetus to further development of biomarker tests for TDP-43 in living people, potentially as part of developing preventative treatments.
Healthcare Economics
Cost of Dementia in Medicare Managed Care: A Systematic Literature Review. P. Fishman et al. The American Journal of Managed Care August 2019 // Paul Fishman, Lindsay White, Norma Coe, Paul K. Crane, Sungchul Park, Bailey Ingraham, Eric B. Larson
A recent systematic review that includes ADRC researchers found that most cost-analyses are backed by limited and dated evidence. Researchers identified and reviewed as many papers as possible from 1983 to 2018 that reported direct costs of older adults with Alzheimer’s disease or related dementias in Medicare managed care plans.
While more and more people are enrolling in Medicare managed care, few papers report the care costs that individuals with Alzheimer’s disease or related dementias can be expected to pay within these private health plans. Only a single study reports data less than 10 years old. These studies not only present out of date data, but also estimate annual costs for people with these forms of dementia with wide variability and use different study populations and methods. This makes comparisons between studies difficult, and relevance to policy less significant.
Medicare managed care enrollment is expected to continue to grow, and the cost of healthcare from individuals with Alzheimer’s and related dementias is large and rising. This review suggests that research into the cost of these disorders within managed care needs to be more consistent, up to date, and detailed to provide more useful insights.
*Only UW-affiliated researchers and collaborators are listed
