Lab

Michael Hornberger's Lab

Featured projects (1)

Project
To explore potential markers of preclinical vascular cognitive impairment (VCI). The research examines differing ERP and connectivity presentations between middle-age individuals at risk of vascular cognitive impairment compared to healthy age-matched controls using EEG.

Featured research (4)

Detection of incipient cognitive impairment and dementia pathophysiology is critical to identify preclinical populations and target potentially disease modifying interventions towards them. There are currently concerted efforts for such detection for Alzheimer's disease (AD). By contrast, the examination of cognitive markers and their relationship to biomarkers for Vascular Cognitive Impairment (VCI) is far less established, despite VCI being highly prevalent and often concomitantly presenting with AD. Critically, vascular risk factors are currently associated with the most viable treatment options via pharmacological and non-pharmacological intervention, hence early identification of vascular factors have important implications for modifying dementia disease trajectories. The aim of this review is to examine the current evidence of cognitive marker correlates to VCI pathology. We begin by examining midlife risk factors that predict VCI. Next, discuss preclinical cognitive hallmarks of VCI informed by insights from neuropsychological assessment, network connectivity and ERP/EEG experimental findings. Finally, we discuss limitations of current cognitive assessments and the need for future cognitive test development to inform diagnostic assessment. As well as, intervention outcome measures for preclinical VCI. In turn, these tests will inform earlier detection of vascular changes and allow implementation of disease intervention approaches.
Docosahexaenoic acid is the main long-chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30-40% of fatty acids in the grey matter of the human cortex. Although the influence of docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer's disease. We investigated the cross-sectional relationship between docosahexaenoic acid levels and the major structural and cognitive markers of preclinical Alzheimer's disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum docosahexaenoic acid (DHA, including lysophosphatidylcholine DHA) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non APOΕ ε4 carriers. APOE also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and APOE on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for Alzheimer's disease in an independent population of APOE genotyped adults (n = 46). APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against cognitive decline should consider APOE ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on Alzheimer's disease progression in APOE ε4 carriers.
The Virtual Supermarket Task (VST) and Sea Hero Quest detect high-genetic-risk Alzheimer`s disease (AD). We aimed to determine their test-retest reliability in a preclinical AD population. Over two time points, separated by an 18-month period, 59 cognitively healthy individuals underwent a neuropsychological and spatial navigation assessment. At baseline, participants were classified as low-genetic-risk of AD or high-genetic-risk of AD. We calculated two-way mixed effects intraclass correlation coefficients (ICC) for task parameters and used repeated measures ANOVAS to determine whether genetic risk or sex contributed to test-retest variability. The egocentric parameter of the VST measure showed the highest test-retest reliability (ICC = .72), followed by the SHQ distance travelled parameter (ICC = .50). Post hoc longitudinal analysis showed that boundary-based navigation predicts worsening episodic memory concerns in high-risk (F = 5.01, P = 0.03), but in not low-risk, AD candidates. The VST and the Sea Hero Quest produced parameters with acceptable test-retest reliability. Further research in larger sample sizes is desirable.
Path integration spatial navigation processes are emerging as promising cognitive markers for prodromal and clinical Alzheimer’s disease (AD). However, such path integration changes have been less explored in Vascular Cognitive Impairment (VCI), despite neurovascular change being a major contributing factor to dementia and potentially AD. In particular, the sensitivity and specificity of path integration impairments in VCI compared to AD is unclear. In the current pilot study, we explore path integration performance in early-stage AD and VCI patient groups and hypothesize that: (i) medial parietal mediated egocentric processes will be more affected in VCI; and (ii) medial temporal mediated allocentric processes will be more affected in AD. This cross-sectional study included early-stage VCI patients (n = 9), AD patients (n = 10) and healthy age-matched controls (n = 20). All participants underwent extensive neuropsychological testing, as well as spatial navigation testing. The spatial navigation tests included the virtual reality “Supermarket” task assessing egocentric (body-based) and allocentric (map-based) navigation as well as the “Clock Orientation” test assessing egocentric and path integration processes. Results showed that egocentric integration processes are only impaired in VCI, potentially distinguishing it from AD. However, in contrast to our prediction, allocentric integration was not more impaired in AD compared to VCI. These preliminary findings suggest limited specificity of allocentric integration deficits between VCI and AD. By contrast, egocentric path integration deficits emerge as more specific to VCI, potentially allowing for more specific diagnostic and treatment outcome measures for vascular impairment in dementia.

Lab head

Michael Hornberger
Department
  • Norwich Medical School

Members (7)

Eneida Mioshi
  • University of East Anglia
Emma C Flanagan
  • University of East Anglia
Gillian Coughlan
  • Harvard Medical School, Massachusetts General Hospital
Vaisakh Puthusseryppady
  • University of East Anglia
Stephen Jeffs
  • University of East Anglia
Ellen Lowry
  • University of East Anglia
Celina Dietrich
  • University of East Anglia