Brain Research New Zealand - Rangahau Roro Aotearoa, April 2021 conference abstracts
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proceedings
Brain Research
New Zealand – Rangahau
Roro Aotearoa, April 2021
conference abstracts
Supercharging priming effects of the inter- Prediction is
vention in a laboratory setting.
rehabilitation: difficult, especially
Aspects of this work included
neuroscience refining parameters to max- about the future
meets practice imise corticomotor excitabil- M-C Smith,1,2,3 PA Barber,1,3
D Taylor, S Olsen, I Niazi, G Alder,
1 1 2 1 ity and exploring effects on BJ Scrivener,1,3 CM Stinear1
U Rashid,1 M Jochumsen,3 P Kaur,1 impairments such as muscle 1
Department of Medicine,
N Kumari,2 N Signal1 weakness and voluntary acti- 2
Department of Exercise Sciences,
vation. The laboratory-based University of Auckland, Auckland,
1
Rehabilitation Innovation Centre,
system presented challenges 3
Neurology, Auckland District
Health and Rehabilitation Research
Institute, Auckland University of
to clinical translation due to Health Board, Auckland
Technology, Auckland. 2Centre size, technical set up, and the Background
for Chiropractic Research, New need for skilled operators. To Stroke affects around 10,000
Zealand College of Chiroprac- overcome these limitations we people in New Zealand each
tic, Auckland. 3Department of miniaturised the device, cre- year, with most experiencing
Health Science and Technology, ating a unique system for EEG impaired motor function. Motor
Aalborg University, Denmark. acquisition and analysis. The recovery is crucial for regaining
Recent and ongoing advances resulting wearable prototype independence, but difficult to
in technology offer huge poten- was a finalist in Callahan In- predict based on clinical judge-
tial to advance exercise-based novation’s national technology ment alone. Over the last de-
rehabilitation. However, we challenge. This work involved cade we have developed clinical
need to ensure these advances collaboration with a commer- tools that combine standardised
are based on sound evidence cial partner (Exsurgo Rehabil- assessments with biomarkers
and importantly have a good fit itation), as well as input from to accurately predict motor out-
with clinical practice. The trans- a team of clinicians, engineers, comes for individual patients.
lational link from neuroscience industrial designers, and peo- The PREP2 tool predicts hand
research to clinically feasible ple with stroke. A user-centred and arm outcome; the TWIST
rehabilitation interventions design approach was used to tool predicts both whether and
is a focus of our work. We are explore the acceptability and when a patient will be able to
currently investigating different usability of exciteBCI in a clin- walk independently again.
neuromodulatory approaches, ical setting. We are currently
Methods and results
including transcranial direct undertaking a dose-finding and
The Time to Walking Inde-
current stimulation and noisy technical feasibility study using
pendently after Stroke (TWIST)
galvanic vestibular stimulation exciteBCI combined with home-
tool was derived and internally
combined with exercise-based based physiotherapy for people
validated with a sample of 124
rehabilitation to determine their following stroke. We believe
patients (55 women, median age
feasibility and clinical effects. that this stepwise, user-centric
71 years; 89 non-ambulatory),
approach to rehabilitation
To exemplify our user-based recruited at two sites within
technology development is vital
translational approach to the 7 days of stroke. Cox hazard
prior to commercialisation and
transformation of a labora- regression analyses were used
clinical implementation of re-
tory-based system to a wear- to identify predictors and
habilitation technologies such
able rehabilitation device, we combine them as a TWIST score.
as exciteBCI.
present exciteBCI. This is a This score is calculated 7 days
non-invasive neuromodulatory We are grateful for financial after stroke using four routine
device which pairs an electro- support for this research from: bedside clinical assessments.
encephalography (EEG) signal, Brain Research New Zealand, The TWIST score predicts
the movement-related cortical Callaghan Innovation, Health the probability of achieving
potential, with peripheral elec- Research Council of New Zea- independent walking at 4, 6,
trical stimulation. land, AUT PBRF Funding, and the 9, 12, or 26 weeks after stroke
Medical Technologies Centre of for individual patients. The
Our initial research focused Research Excellence. internally validated model was
on understanding the cortical
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NZMJ 30 July 2021, Vol 134 No 1539
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www.nzma.org.nz/journalproceedings
at least 89% accurate for all time To further delineate the early A novel dopamine
points, except 4 weeks post- molecular events in HD we as- pathway:
stroke (82%). sessed gene expression changes
in the striatum of a prodromal
Characterization
Future directions
sheep model, OVT73, express- and implications for
The TWIST tool is being
validated and updated with an ing a full length human CAG-ex- Parkinson’s disease
ongoing study recruiting a new panded HTT cDNA transgene.
PS Freestone, KL Todd, J Lipski
cohort of patients. This study Results were further explored
through metabolite and gene Department of Physiology,
will also identify barriers and Centre for Brain Research, Brain
facilitators to future imple- expression analyses in brain
Research New Zealand, Univer-
mentation of TWIST in routine tissue from HD cases.
sity of Auckland, Auckland
clinical care. Methods Aim
RNA-sequencing (RNA-seq) The precise timing and
Exploring urea was performed on striatal tis- location of dopamine release
sue from 5-y-old OVT73 sheep underlies many brain functions
cycle dysfunction (n = 6), with quantified gene ex- including motor, memory/learn-
as the origin of pression compared to matched ing and cognition processes.
neuropathogenesis in controls (n = 6). Based on the Recent anatomical evidence
Huntington’s disease RNA-seq results the metabolite suggests a novel dopamine
urea and genes involved in the pathway originating in the sub-
RR Handley,1 SJ Reid,1 R Brauning,2 urea cycle were assessed by stantia nigra pars lateralis (SNL)
P Maclean,2 ER Mears,1 I Fourie,1 enzymatic assay and quantita- and terminating in the most
S Patassini,3,4 M Grant,1 K Lehnert,1 tive real-time polymerase chain caudo-lateral part (tail) of the
GJS Cooper,1,4 SR Rudiger,5 reaction (qRT-PCR) respectively, striatum. Unlike neighboring
CJ McLaughlan,5 PJ Verma,5 in brain tissue from OVT73 and pars compacta (SNc) dopamine
JF Gusella,6 ME MacDonald,6 HD cases. neurons and their projection to
HJ Waldvogel,3 CS Bawden,5
Results and conclusions the dorso-lateral (center) stria-
RLM Faull,3 RG Snell1
We identified significantly tum, this novel pathway is yet to
1
Centre for Brain Research, School be functionally characterized.
increased levels of the urea
of Biological Sciences, The Universi-
ty of Auckland, Auckland, 2Invermay transporter SLC14A1 in the Methods
Agricultural Centre, AgResearch OVT73 striatum, along with Electrochemical detection
Ltd., Mosgiel, 3Centre for Brain other important osmotic reg- of basal and evoked dopamine
Research, Faculty of Medical and ulators. Further investigation release was conducted in the
Health Science, The University of revealed elevated levels of the striatum of anesthetized Wistar
Auckland, Auckland, 4Centre for metabolite urea in the OVT73 rats. Basal dopamine was mea-
Advanced Discovery and Experi- striatum and cerebellum, and sured at various depths in both
mental Therapeutics, Division of
post-mortem human brain the center and tail striatum.
Cardiovascular Sciences, School of
from HD cases, including those Evoked dopamine release was
Medical Sciences, Faculty of Biology,
Medicine and Health, University of with low-level neuropathology measured in these two striatal
Manchester, Manchester, United (Vonsattel grade 0/1). Urea is regions in response to electrical
Kingdom, 5Molecular Biology and the waste product of protein stimulation of key basal ganglia
Reproductive Technology Labora- catabolism, generated from nuclei.
tories, South Australian Research ammonia via the urea cycle. El-
and Development Institute, Results
evation of urea in the absence
Adelaide, Australia, 6Molecular Measurement of basal
of the overt cell loss is further
Neurogenetics Unit, Center for dopamine revealed distinct
evidence that protein catabo-
Genomic Medicine, Massachusetts dopamine domains in the dorsal
lism is increased in HD brain,
General Hospital, Boston, USA (330±60 nM) and ventral regions
possibly as an alternate energy
Aims of the center striatum (395±65
source given the generalized
Huntington’s disease (HD) is nM; n=6), and a single domain
metabolic defect in HD. Excess
a neurodegenerative disorder in the tail (249±31 nM; n=7).
urea or ammonia are known to
characterised by extensive Electrical stimulation of the me-
cause neurologic impairment in
loss of striatal neurons, with dial forebrain bundle contain-
other disease contexts. As such,
progressive chorea, dementia, ing projections to the striatum,
our findings indicate that ab-
and psychological disturbance. evoked dopamine release in
errant urea metabolism could
It is caused by an expanded the center and the tail striatum,
be the primary biochemical
polyglutamine repeat (CAG) albeit smaller in amplitude
disruption initiating neuro-
in the huntingtin gene (HTT). and less consistent in the latter
pathogenesis in HD.
The pathogenic mechanism (center: 221±28 nM; tail: 24±4
resulting in cell dysfunction This work was kindly support- nM). As expected, stimulation
and death beyond the causative ed by the Cure Huntington’s Dis- of the SNc evoked release in the
mutation is not well defined. ease Initiative Foundation and center striatum (57±13 nM) but
Brain Research New Zealand. surprisingly none in the tail,
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while stimulation of the SNL Methods Aim
had the opposite effect (tail: Parkinsonian rats were Many people with Parkinson’s
24±9). Finally, stimulation of produced by unilateral injection disease experience hallucina-
the subthalamic nucleus evoked of 6-hydroxydopamine into tions and their development
release only in the tail striatum the medial forebrain bundle. associates with high caregiv-
(36±8), confirming the prefer- Glutamatergic Mthal neurons er-burden, hospital admissions
ential innervation of the SNL by were transduced to express and institutionalisation. Clini-
this nucleus. an opsin following injection cians have observed that hallu-
of an adeno-associated viral cinations often occur before the
Conclusion
vector (AAV.CaMKII.XXX.GFP). development of dementia, and
This study provides the first
Optogenetic stimulation was thus, are thought to increase
functional characterization of
applied with blue or orange dementia risk. The predictive
the novel dopamine pathway
light and forelimb akinesia was value of hallucinations and
and identification of distinct
assessed using skilled reaching, other neuropsychiatric symp-
dopamine domains in the stri-
and cylinder and step-tests. toms, however, have not been
atum. Given the role of the tail
Experimenters were blind to the compared to clinical and demo-
striatum in processing sensory
specific opsin used. graphic predictors of dementia.
information, findings from this
We aim to determine if they are
study may shed light on the Results and conclusion
Forelimb use significantly useful markers of dementia risk.
often overlooked and untreated
non-motor symptoms of Parkin- increased in the reaching test Methods
son’s disease. when orange light was applied 328 Parkinson’s participants
using 2 patterns—15 Hz tonic completed baseline neuropsy-
and a physiological pattern chiatric and cognitive assess-
Specific patterns of
previously recorded from a ments. Of these, 202 non-de-
optogenetic stimulation Mthal neuron in the healthy mented participants were
of glutamatergic motor state (control reaching, Pproceedings
PDQ-anxiety. In contrast, cogni- activities such as reading or for poorer hearing in adulthood.
tive ability (delta ELPD = 36 (SD watching movies. Finally, I will Combined with evidence that
8)) and age (delta ELPD = 11 (SD discuss ways in which my lab mid-life hearing loss is a signif-
5)) provided useful predictive is working towards making icant modifiable risk factor for
information of future PDD. these techniques more widely cognitive impairment, this sug-
Conclusion
available. Although infrared gests a potentially modifiable
Cognitive ability and age eye-tracking is increasingly in- trajectory from sensory to cog-
strongly out-performed neuro- corporated into consumer tech- nitive decline, that begins early.
psychiatric measures, including nologies such as virtual reality We aim to develop interventions
hallucinations, as markers of headsets, access to dedicated to improve sensory processing
developing dementia within hardware remains a barrier to and cognition that would be
four-years. Therefore, hallucina- adoption of eye-tracking as a feasible and acceptable for all
tions and other neuropsychiat- means of measuring behaviour. New Zealanders.
ric symptoms do not appear to I will describe how the built-in Method
be useful markers of dementia imaging capabilities of ubiq- Participants in Phase 1 assess-
risk. uitous technologies—such as ment study were adults with
tablets and smart phones—can suspected MCI, older healthy
be leveraged to provide basic controls and younger control.
Diagnosis and eye tracking for (eg, home-moni- Hearing, visual acuity and audi-
monitoring of neuro- toring applications). tory and visual processing were
degenerative disorders Conclusion assessed using behavioural,
using eye-tracking Eye-tracking then, provides a EEG and self-report measures.
means of objectively character- Feasibility of training, using
S Dakin
izing a whole range of patients’ in-person and online formats,
Department of Optometry day-to-day visually-guided has been explored in Phase 2.
and Vision Science, University
activities. This wealth of in- Results
of Auckland, Auckland
formation—when paired with The MCI group had greater
Aim
high throughput data analyses self-reported hearing difficul-
Understanding sensory defi-
now achievable with machine ties, and poorer auditory tempo-
cits associated with neuro-de-
learning—has the potential ral and visual motion percep-
generative disease is important
to support a patient-centred tion scores. Lower MoCA scores
both to illuminate the neural
approach to the diagnosis and were associated with greater
bases of these conditions and to
management of neuro-degener- self-reported hearing difficulties
improve how they are diag-
ative disease. and slower cortical auditory
nosed and treated. In this talk I
will describe how behavioural evoked potentials. Phase 2 train-
assessment based on eye Audition and vision: ing trials using auditory training
movements has the potential links with cognition and global motion perceptual
to transform assessment of not in older adults training highlight the need for
only visual but also cognitive training to be motivating and
function. SC Purdy,1,2,3 JH Leung,1,2,3 LM Hamm,4 for technology to be accessible
SC Dakin,2,4 OM Cañete,1,3 for older adults who have com-
In terms of vision, humans A Kuruvilla-Mathew,1,3 K Brewer,2,4 puter anxiety or low computer
rely on the oculomotor system TW Taki,1,2 LJ Tippett,1,2 PR Thorne2,3,4 self-efficacy. Preliminary data
to maintain a stable, sharp view School of Psychology, University
1 from younger participants
of the world. Having briefly of Auckland, Auckland, 2Brain suggest cognitive flexibility and
reviewed the main classes of oc- Research New Zealand—Rangahau executive function may improve
ulomotor dysfunction observed Roro Aotearoa, 3Eisdell Moore with auditory training.
in neurodegenerative disease Centre for Hearing and Balance
Research, 4Faculty of Medical Conclusion
(eg, saccade generation) I will
and Health Sciences, University Further work is needed to
discuss how eye-tracking para-
of Auckland, Auckland develop and trial engaging
digms (eg, saccadic remapping)
Aim training technology that is
can also help us explore general
Longitudinal studies and accessible and efficacious
brain processing “strategies”
metanalyses show associations for older adults, including
(eg, predictive coding). I will
between hearing and vision those experiencing auditory
next describe how eye-tracking
impairment and cognition. processing difficulties from
can be used to explore non-visu-
Clinical trials are assessing the other neurological conditions.
al brain function both through
efficacy of hearing treatment Research by our team (Purdy,
(a) targeted tests, such as cog-
in reducing cognitive decline Brewer, Taki) with Māori stroke
nitive assessment based wholly
in elders with hearing loss but survivors highlights that iwi
on fixation and (b) free-viewing
auditory/visual training effects are motivated and resourceful
paradigms: analysis of patterns
on cognition have not been and willing to engage with new
of fixation acquired while
determined. Poorer childhood technological solutions for their
patients engage in everyday
hearing appears to increase risk communities.
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Metaphorically This research was funded by relation between physical
speaking: exploring the BRNZ and Ageing Well National activity and cognition chron-
Science Challenge. ically, but not acutely in healthy
needs of Pacific families adults; behavioural regulation
affected by age-related of stress exposure is a key
Potential and pitfalls
cognitive impairment methodological consideration
with exercise and when studying and interpreting
V Symon, P Norris, R Richards, environmental stress cerebrovascular and cognitive
T Mapusua
for brain health effects of exercise and envi-
Centre for Pacific Health, ronmental stressors; effects of
University of Otago, Dunedin JD Cotter,1 TD Gibbons,1,2,3
aerobic fitness on cerebrovascu-
Aim KN Thomas,2 LC Wilson,3 L Machado4
lar function remain equivocal,
Pacific populations in New 1
School of Physical Education, Sport as does the identification of a
Zealand are aging, but little is and Exercise Sciences, 2Department
valid and sensitive measure of
known about Pacific people’s of Surgical Sciences, 3Department of
Medicine, 4Department of Psychol-
cerebrovascular health. None-
experiences of or views about theless, an inter-disciplinary
ogy, University of Otago, Dunedin
cognitive impairment and their approach has strong potential
experiences in the health care Aim
To briefly highlight (a) crucial to enhance brain health using
environment. The aim of this novel combinations of exercise
research is to explore the needs inter-dependencies between
brain health, physical activity, and environmental stress.
of Pacific peoples and their
families affected by age related and the stressors of natural
cognitive decline. environments, (b) the relevance Ka ora ai te iwi:
of cerebrovascular function, Māori whānau lived
Methods (c) methodological challenges
Six health care service pro- experiences of mate
and opportunities in research
viders with a focus on Pacific using human participants, and
wareware (dementia)
patients were interviewed to (d) gaps in knowledge for which J Wharewera-Mika (Ngāti Awa, Ngāi
determine services available our group could contribute. Tūhoe, Te Whānau ā Apanui)
to aged Pacific peoples, access
Methods University of Auckland, Auckland
to those services and whether
available services met Pacific We assess and manipulate Aim
people’s needs. cerebrovascular haemodynam- To explore the cultural ‘lived’
ics and its determinants (esp. experiences of Māori (Indige-
Results arterial CO2 and O2 pressures nous people of Aotearoa New
Barriers in accessibility of and hydrostatic pressure) in Zealand), directly impacted by
services, getting a diagnosis, response to acute and chron- mate wareware (dementia) and
communication and language ic exercise or environmental their wider support whānau (ex-
were identified as key concerns stressors, in healthy and tended family), to understand
by participants. Many Pacific diseased human cohorts. The whānau needs, and provide
people experienced a lack of cerebrovasculature responds advice for culturally responsive
information and therefore poor strongly to arterial CO2 pres- approaches to enhance ‘ka ora
access to services. The provision sure and thereby provides a ai te iwi’ (flourishing together).
of information solely via online key indicator of cerebrovas-
fora exacerbated the economic Methods
cular function. Parameters of
disadvantages some faced, due Kaupapa Māori research
stress—esp. intensity, duration,
to a lack of access to a computer methods and ethics informed
pattern—all impact on cere-
or the internet. Diagnosis was and guided this study. We in-
brovascular function; these can
often made difficult by inconsis- terviewed 20 whānau impacted
be manipulated independently
tent access to general practi- by mate wareware in the Ngāti
and in combination (eg, static
tioners in lower socio-economic Awa region (of Whakatāne).
resistance exercise with(out)
areas and long wait times. Thematic and participatory-ac-
a Valsalva manoeuvre, and/or
Communication was hindered tion approaches were utilized to
heat stress with(out) exercise or
by lack of access to information analyse narratives and collabo-
orthostatic/gravitational stress).
in Pacific languages that incor- ratively develop advice.
porated a Pacific world view. Results and conclusion
Results
There was also a lack of health As examples: Exercise and en- Commonly Māori care for
workers across all sectors who vironmental stressors modulate whānau with mate wareware
spoke Pacific languages, and cerebral and cerebrovascular for the full duration of illness of-
understood their cultural needs. function via local, humoral and ten navigating the journey with
systemic mediators but their limited specialist support. The
Common themes noted by all dose-vs-response relations are
collective caring role is not ex-
of the participant healthcare minimally determined, even perienced as burdensome how-
providers and support services for singular stressors; habitual ever was often a distressing ex-
indicated the needs of aged physical activity and fitness are perience particularly during the
Pacific people experiencing related but distinct constructs; later stages of illness. Preven-
cognitive decline were often not cerebrovascular function tion and cure were considered
being met. appears to partly mediate the important however the priority
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for whānau was for increased co-design approach. Two focus Is a dementia
access to mātauranga Māori groups were held; one with prevalence study
mate wareware information, kaumātua (Māori elders) and
opportunities to connect with one with rangatahi (younger
feasible in Aotearoa
other mate wareware whānau, Māori) to ascertain what mate- New Zealand?
access supports to manage and rial should be included in the S Cullum,1,2 A Martinez-Ruiz,1,2,3
cope with the illness progres- app. The focus groups were au- S Yates,1,2 M Dudley,1,2 G Cheung,1,2
sion and culturally-responsive dio-recorded and transcribed. R Krishnamurthi,1,4 F Fa’alau,1,2
respite care options. Service Data were analysed to identify E Ma’u,2 C Rivera-Rodriguez,1
provision enhancing ‘ka ora recurring ideas and themes; D Exeter,1,2 L Tippett,1,2 N Kerse,1,2 and
ai te iwi’ requires a whānau these were used to guide the the Living with Dementia in Aotearoa
ora (collective ‘whole whānau’ design and development of (LiDiA) Research Group
wellbeing) approach to care, the mobile app. Whānau had 1
Brain Research New Zealand,
embracing tikanga-based prac- ongoing input during app de- 2
The University of Auckland,
tices responsive to the cultural velopment. Auckland, 3National Institute of
and spiritual needs of Māori Results Geriatrics of Mexico, Mexico City,
alongside physical and psycho- The analyses identified Mexico, 4Auckland University
logical health needs. In addi- important aspects of mate ware- of Technology, Auckland
tion to increasing the cultural ware that should be included Aim
capability of supports, specialist in the app. These included: (1) New Zealand requires accu-
care may be best placed within the physical, emotional and psy- rate data regarding the extent
existing whānau ora health and chological aspects of dementia, of dementia and impact on
wellbeing structures. (2) the availability of diagnostic people and whānau living with
Conclusion services and the diagnostic dementia to help inform a na-
Māori suffer many health and process, (3) coping strategies, (4) tional dementia plan, but to date
social inequities and those car- information regarding dementia there has never been a national
ing for whānau with mate ware- management and care services, dementia prevalence study. Our
ware are likely to be disadvan- and (5) insight from different study aims to assess the feasi-
taged twofold. A systems level generations in the whānau to bility of conducting a communi-
approach advocating Te Tiriti ensure the app would appeal ty-based dementia prevalence
o Waitangi-based partnership to all ages. The researchers study in the major NZ ethnic
and collaboration is necessary identified three target audiences groups, using the 10/66 demen-
to address exacerbated health for the app: (1) whānau living tia assessment protocol which
inequity. with mild cognitive impairment, measures dementia and its psy-
(2) the caregivers of whānau chological and financial impact
Acknowledgements: Eru on family carers.
living with mate wareware,
Thompson Postdoctoral Research
and (3) healthy younger people. Methods
Fellowship, Brain Research New
Further criteria for the compo- First, we evaluated the
Zealand.
sition of the app were: (1) the diagnostic accuracy of adapt-
utilisation of te reo Māori and ed/translated 10/66 dementia
Te Ōranga Ō te Roro: Māori-friendly language, (2) assessment protocols in older
a phone app for mate Māori characterisation using people (≥65 years) from Māori*,
wareware (dementia) Māori audio and graphics, and Samoan, Tongan, and Fijian
(3) inclusion of video interviews Indian communities. Then we
M Dudley,1,2 M King,3,4 H Spooner,5 with Māori health workers assessed meshblock sampling
S Olsen,5 S Cullum,1,2 A Merkin,5 and whānau living with mate methods and the accuracy and
E Ramirez-Rodriguez,6 B Nepia,7 wareware. acceptability of the 10/66 tool
B Kaa,7 A Martinez,1,2 C Reihana,1 in these same populations (in
Conclusion
S Yates1,2 addition to Chinese and NZ Eu-
The ‘mate wareware’ web-
Brain Research New Zealand,
1
based app provides information ropean people aged 65+) living
2
The University of Auckland, in two areas of South Auckland
about the possible prevention,
Auckland, 3 MedTech, 4Callaghan (Favona North and Mission
Innovation, 5Auckland Univer-
diagnosis, and management of
mate wareware for whānau. Heights).
sity of Technology, Auckland, 6
Victoria University of Wellington, The app will be further devel- Results
Wellington, 7Counties Manukau oped and enhanced as future 1278/1607 (80%) houses
District Health Board, Auckland funding becomes available. answered the door and 272/1278
Aim The address to access the cur- (21%) houses had occupants
To develop a Māori-friendly rent web-based app is: www. aged 65+ (377 people aged
mobile app that provides infor- matewareware.co.nz 65+ in total). 2018 census data
mation about mate wareware. overestimated Māori and NZ
This study was funded by
Methods European 65+ populations,
Brain Research New Zealand and
This research utilised a and underestimated Asian
MedTech Centres of Research
combined kaupapa Māori and 65+ populations several fold.
Excellence
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The response rate was 30% for tion of thalamic head direction 1
Department of Anatomy and
in-person interviews conducted cells and hippocampal place Medical Imaging, 2Centre for Brain
simultaneously with participant cells. Likewise, hearing loss has Research, 3School of Psychology,
4
School of Optometry and Vision
and informant, but 70% when also been associated with an
Science, 5Department of Ophthal-
conducted with participant increased risk of dementia. The
mology, University of Auckland,
only. Interview response rate aim of this study was to explore Auckland, 6Department of Anatomy,
was T),
A number of studies in hu- relationship between age-relat- or non-carrier controls. We en-
mans have reported that spatial ed spatial memory deficits and rolled 25 participants between
memory impairment with cVEMP deficits in humans. 15 April 2016 and 19 Septem-
aging is significantly predicted ber 2018. Participants have
Supported by a grant from the
by deficits in cervical vestibu- undergone annual assessments
Marsden Fund to PFS and YZ.
lar-evoked myogenic potentials consisting of medical history,
(cVEMPs), indicative of saccular neurological and physical exam-
function. Age-related cVEMP The NZ Genetic inations, a comprehensive neu-
deficits have also been linked Frontotemporal ropsychological battery, tests
statistically to hippocampal Dementia Study of autobiographical memory
atrophy and an increased risk of
(FTDGeNZ): the and social cognition, structural
Alzheimer’s Disease. These re- and functional MRI, olfactory
sults are consistent with animal first 5 years
testing, retinal imaging, and
studies that have demonstrated B Ryan,1,2,8 A Baker,2,3,8 C Ilse,2,8 collection of blood samples for
that mice without otoconia, but KL Brickell,2,8 HM Kersten,4 analyses of microRNA and pro-
with normal semi-circular canal HV Danesh-Meyer,5 JM Williams,6,7,8 tein fluid biomarkers. We have
function, exhibit spatial mem- DR Addis,3,9,10 LJ Tippett,2,3,8 developed an online journaling
ory deficits as well as dysfunc- MA Curtis1,2,8 platform for participants to
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record their lived experiences of research in the future, will be New and emerging
genetic FTD. discussed. magnetic resonance
Results DPRC participants undergo imaging techniques
Genotyping has identified detailed clinical, neuropsycho- in mild cognitive
6 pre-symptomatic mutation logical, neuroimaging, lifestyle
carriers and 19 non-carrier
impairment and
evaluations and blood dona-
controls in the cohort. Baseline tions, which also inform clinical
Alzheimer’s disease.
analyses of retinal imaging classifications by multidisci- C Morgan,1,2,3 T Manson,4 V Suresh,4,5
data revealed no differences plinary teams. Amyloid PET J Govender,2 D Jansson,6 D Thomas,7
in retinal layer thickness or (florbetaben, FBB) is a recent X Shao,8 D Wang,8 M Günther,9
perfusion between carriers and addition. In January 2021, 321 M Dragunow,2,10,* L Tippett1,2,*
non-carrier controls. To date, participants had been assessed, 1
School of Psychology and Centre for
19 participants have completed with 261 enrolled (227 clinical Brain Research, University of Auck-
3 annual assessments, which is participants: Subjective cogni- land, 2Brain Research New Zealand
designated as our first longitudi- tive decline = 62; mild cognitive - Rangahau Roro Aotearoa, 3Centre
nal dataset. impairment (MCI) = 128; early for Advanced MRI, University of
Conclusion dementia = 26). APOE genotyp- Auckland, 4Auckland Bioengineering
ing further characterises our Institute, University of Auckland,
We have established the 5
Department of Engineering Science,
first longitudinal study of FTD sample.
University of Auckland, Auckland,
in NZ. Longitudinal analyses Department of Psychiatry and
Current research studies 6
of this cohort will contribute aim to identify biomarkers Behavioural Sciences, University of
to the search for the earliest Washington, USA, 7University College
predicting worsening MCI (eg,
pre-symptomatic biomarkers London, United Kingdom, 8University
blood-proteins, microRNAs, neu-
of FTD. of Southern California, USA, 9Fraun-
roimaging analyses combined hofer Institute for Digital Medicine,
with neuropsychology, use of Bremen, Germany, 10Department of
Faull lecture: the LTP, EEG and dynamic causal Pharmacology, University of Auck-
journey of the Dementia modelling). A secondary objec- land, Auckland. *Joint senior authors
Prevention Research tive is to identify mechanisms Aim
underlying these conditions (eg, The blood-brain barrier (BBB)
Clinics and their faulty blood-based barrier, iron is a specialised structure that
people: past, present deposition), and to understand selectively restricts the entry of
and the future the experience of individuals potentially toxic components
and their whānau (eg, factors into the brain. Evidence to date
LJ Tippett1,2,3,4 and the Dementia
influencing well-being). Finally, supports BBB “leakage” as an
Prevention Research Clinics,
two intervention studies are early event in the development
New Zealand
underway to test novel methods and progression of neurode-
1
Centre for Brain Research, to delay progression of MCI to generative disorders such as
University of Auckland, Auckland,
dementia. Parkinson’s, motor neuron and
2
School of Psychology University
of Auckland, Auckland, 3Dementia Alzheimer’s disease (AD). Mag-
Many challenges will be dis-
Prevention Research Clinics, netic resonance imaging (MRI)
cussed, including the COVID-19
4
Brain Research New Zealand— is commonly used to measure
pandemic, and how, despite
Rangahau Roro Aotearoa BBB function with contrast
guidance from kuia Dr Waiora
Aim agents that cannot cross an in-
Port, we have not yet engaged
Over the last five years the tact barrier. Our aim was to test
sufficient Māori participants,
Dementia Prevention Research and further develop a new MRI
with participation from Pasifika
Clinics (DPRCs) have trans- method that tracks the move-
communities even lower.
formed from an aspiration ment of water molecules as
into a multi-centre, multi-disci- The heart of the DPRCs are they permeate across the BBB,
plinary, longitudinal research its people: the dedicated, highly providing a safer and potential-
study. The aim is to identify expert staff; and most centrally ly more sensitive marker of BBB
factors underlying the develop- the participants, who volunteer dysfunction.
ment and progression of mem- to be part of this journey, and to Methods
ory problems and dementia in be partners in this research. Arterial spin labelling (ASL)
the unique cultures and ethnic- MRI magnetically “labels”
Acknowledgements: Partic-
ities of Aotearoa. Each of the arterial blood and by subtracting
ipants, research and clinical
clinics (Auckland, Christchurch, labelled and unlabelled images,
staff of the Dementia Prevention
Dunedin) has its own flavour, perfusion maps are generated.
Research Clinics. Funding from
challenges and successes. This By collecting data at a range of
Alzheimer’s New Zealand Char-
lecture provides an overview of times after labelling, it is possible
itable Trust, The Angus Trust,
DPRC development, their cur- to model the intra- and extra-
Brain Research New Zealand
rent state including associated vascular components of the ASL
and the New Zealand Dementia
research projects, and opportu- signal and derive a transfer rate,
Prevention Trust
nities provided by the DPRCs for
93
NZMJ 30 July 2021, Vol 134 No 1539
ISSN 1175-8716 © NZMA
www.nzma.org.nz/journalproceedings
Kw, of labelled water molecules 1
Centre for Brain Research, with the Australian Imaging
across the BBB. We have imple- University of Auckland, 2Dementia Biomarker and Lifestyle group.
mented two different approach- Prevention Research Clinics, 3Brain
Research New Zealand—Rangahau Methods
es most suited to clinical use, To establish the blood bio-
Roro Aotearoa, 4University of
“T2-ASL” and “diffusion-ASL” marker profile within the DPRC,
Gothenburg, Sweden, 5University
and collected data from Demen- College London, London, United samples from 425 visits were se-
tia Prevention Research Clinic Kingdom, 6UK Dementia Research lected from the Auckland, Dune-
participants, with mild cognitive Institute at UCL, London, United din and Christchurch DPRCs,
impairment (MCI), early AD and Kingdom, 7Department of Anatomy, to enable investigation of
age matched controls. School of Biomedical Sciences,
longitudinal trends within 205
University of Otago, Dunedin,
Results and conclusion 8
Brain Health Research Centre,
DPRC participants. In collabora-
Surprisingly, with both University of Otago, Dunedin tion with Professor Zetterberg
methods we find lower Kw in Aim (University of Gothenburg) the
the MCI and AD group com- The pathological hallmarks levels of six neurodegenerative
pared to controls, counter to of Alzheimer’s disease (AD) are blood markers (Aβ1-40, Aβ1-42,
our hypothesis of higher Kw in accumulation of amyloid-beta t-tau, p-tau181, NfL and GFAP)
the presence of a “leaky” BBB. (Aβ), hyperphosphorylated tau will be assessed using the SiMoA
The aquaporin 4 (AQP4) system and neuronal cell loss. Early technology.
at the BBB interface regulates detection of these pathologies Conclusions
water transfer and exchange is critical to timely delivery of Measurement of these blood-
between the cerebrospinal and treatment strategies. Inter- based markers of neurodegen-
interstitial fluids. AQP4-deficient national studies support the eration in DPRC participants’
mice display reduced clearance clinical utility of blood biomark- samples will provide essential
of amyloid-β and separately, ers for early detection, diagnosis characterization of the DPRC
a lower Kw than wild type and monitoring progression of cohort, allowing comparison
animals, using the same T2-ASL AD. Advances in ultra-sensitive and disease-staging with other
method we present. These re- immunoassay methods such as internationally recognised
sults combined, suggest that our Single Molecule Array (SiMoA) biomarker studies. The gleaned
new ASL-MRI water-transfer now allow the assessment of the biomarker information will be
method could be sensitive to an key markers of AD pathology correlated with other forms
alternative mechanism of BBB (Aβ, total-tau (t-tau), phos- of participant information
dysfunction in MCI and AD. phorylated tau (p-tau) species, including neuropsychological
neurofilament light (NfL) and and clinical data, neuroimaging,
Blood biomarkers glial fibrillary acidic protein APOE genotype and other blood-
for the detection and (GFAP)). Our aim is to establish based biomarkers. Together
prediction of disease a longitudinal biomarker profile this information will give an
for the participants of the integrated view of the extent of
progression in Mild Dementia Prevention Research neurodegeneration occurring
Cognitive Impairment Clinics (DPRC). The DPRC Tissue in our cohort and how this
and Alzheimer’s Disease Biobank comprises of serum, changes over the progression of
plasma (EDTA or heparin), disease.
EE Cawston,1,2,3 L Griner,1,2,3
platelets, red and white blood
CYE Wong,1,2,3 C Marais,1,2,3 H This study is funded by Brain
cells prepared from participants
Zetterberg,4,5,6 JM Williams,2,3,7,8 Research New Zealand—Ranga-
according to strict standard op-
L Tippett,1,2,3 Dementia Prevention hau Roro Aotearoa.
erating procedures which align
Research Clinics NZ2,3
URL:
www.nzma.org.nz/journal-articles/brain-research-new-zealand-rangahau-roro-aotearoa-
april-2021-conference-abstracts
94
NZMJ 30 July 2021, Vol 134 No 1539
ISSN 1175-8716 © NZMA
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