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94 Abstracts / Journal of the Neurological Sciences 455 (2023) 121173
Montréal, Department of Medicine, Montreal, Canada, cUniversity of British
Columbia, Medicine, Victoria, Canada, dUniversity of British Columbia,
Medicine, Prince George, Canada, eMcMaster University, Department of
Family Medicine, Kitchener, Canada, fDalhousie University, Department of
Psychiatry, Halifax, Canada, gUniversity of Alberta, Medicine (Neurology),
Edmonton, Canada, hNova Scotia Health Authority, Department of
Psychology, Halifax, Canada, iMcGill University, Department of Family
Medicine, Montreal, Canada, jBaycrest Hospital, Research, Toronto,
Canada, kBaycrest Center, Behavioural Neurology, Toronto, Canada,
l
University of Saskatchewan, Psychology, Saskatoon, Canada, mUniversity
of Saskatchewan, Canadian Center for Health & Safety in Agriculture,
Medicine, Saskatoon, Canada, nMcGill University, Mcgill Center for Studies
in Aging, Verdun, Canada, oBrigham and Women’s Hospital, Psychiatry and
Neurology, Boston, United States of America
Background and aims
Remote cognitive and behavioral assessment offers numerous
potential benefits, including improved access to care. Nevertheless,
telemedicine has limitations, and may be most appropriate for certain
patients. Currently, evidence-based guidance on virtual assessment
readiness is lacking. Patient, caregiver, and environmental factors may
help stratify patients. Our goal is to develop a set of clinical indicators
or “red flags”, using the Delphi method, to determine a patient's
suitability for undergoing remote cognitive and behavioral diagnostic
assessment.
Methods
The Delphi process is an iterative group consensus method, used
here to synthesize expert opinions from a multidisciplinary team of
behavioral neurologists, neuropsychiatrists, neuropsychologists, social
workers, geriatricians, persons with lived experience, and family
practitioners, under the auspices of a workgroup within the Canadian
Consortium on Neurodegeneration in Aging (CCNA). The process
consists of anonymized data collection in three rounds, culminating in
grading red flags on effectiveness, reproducibility, and efficiency.
Consensus is achieved when red flags receive an overall mean score of
4/5 or above.
Results
In the first round, 11 respondents, with an average of 12.4 years of
clinical experience, generated 77 unique potential red flags. Seven
respondents completed the second round, and the third round is
underway.
Conclusions
The Delphi method was used to synthesize expert opinions regarding
patient suitability for remote cognitive diagnosis into a set of red flags.
These flags could serve as a framework to guide clinical decision-
making regarding individual patients' virtual assessment readiness.
Future directions include incorporation of patient and caregiver
perspectives to further enhance decision making.
doi:10.1016/j.jns.2023.121392
121393
Brain extracellular vesicles in psychoticism display novel
molecular clues associated to higher prevalence of age-related
dementia
Fenghe Zhanga, Cristina Lorcaa, Jose Sánchezab, María Muletab, Julia
Lisaab, Aida Serra Maquedaab, Xavier Gallart-Palaua, aBiomedical
Research Institute of Lleida Dr. Pifarré Foundation (IRBLLEIDA), Lleida,
Spain, bUniversity of Lleida (UDL) - Biomedical Research Institute of Lleida
https://www.tarjomano.com https://www.tarjomano.com
Dr. Pifarré Foundation (IRBLLEIDA), Department of Medical Basic Sciences,
Lleida, Spain
Background and aims
Individuals with schizophrenia (SCHZ) display an increased risk for
the development of dementia as they age, however, the molecular
implications behind this condition remain poorly explored. Extracellular
vesicles (EVs) are vastly implicated in brain pathology,
neurodegeneration and dementias but their role(s) in SCHZ is still
unknown. Here, we use state-of-the-art systems biology to elucidate the
molecular composition of brain EVs in SCHZ aiming to uncover
molecular singularities associated to the development of dementia in
SCHZ.
Methods
In this work, discovery-driven clinical neuroproteomics was used to
define at proteome-wide level the compositions of brain EVs from post-
mortem brain tissues (prefrontal cortex, caudate and hippocampus) of
subjects with SCHZ and matched controls (n = 30) obtained by
PROSPR. Bioinformatics was used to pinpoint molecular signs
associated to neurodegeneration and dementia in brain EVs from SCHZ
subjects.
Results
Our data indicated presence of altered molecular mechanisms of
neuroinflammation in brain EVs from SCHZ subjects. These alterations
were previously reported to be associated to neurodegeneration and
dementias. The dementia-associated proteome observed in brain EVs of
SCHZ subjects revealed abnormal modulation of key proteins such as
DPYSL2, GFAP and MBP (p b 0.001).
Conclusions
Identification of altered molecular mechanisms of neuronal insult
associated to neuroinflammation in neurodegenerative dementias and
in SCHZ may provide novel insights in the development of new
therapeutic strategies for these events and may help to prevent or
ameliorate neurodegeneration in SCHZ patients.
doi:10.1016/j.jns.2023.121393
121394
Input of neurologists to the world Alzheimer report 2021 on the
diagnosis of dementia
Serge Gauthiera, Stijn Servaesa, José Moraisb, Claire Websterb, Pedro
Rosa-Netoa, aMcGill University, Center for Studies in Aging, Montreal,
Canada, bMcGill University - Division of Geriatric Medicine, Dementia
Education Program, Montreal, Canada
Background and aims
Input from clinicians was essential to write the World Alzheimer
Report 2021 about current and future diagnosis of dementia.
Methods
On-line 35 questions survey between March and June 2021, sub-
analysis of answers from neurologists.
Results
From the 1110 clinicians who answered the survey, the majority
(32.6%) were neurologists, from 110 countries. The main difficulty they
encountered in their practice for the diagnosis of dementia is the belief
by many other physicians that nothing can be done and/or their lack of
knowledge about diagnosis. Access to imaging facilities for structural
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Abstracts / Journal of the Neurological Sciences 455 (2023) 121173
imaging was good (79%), FDG-PET modest (37%) and amyloid PET low
(24%). Many performed lumbar punctures themselves (49%) or referred
to a colleague with more practical experience (26%) for amyloid and
tau levels. Most (60%) felt comfortable in disclosing the diagnosis of
dementia to the patient, but some (33%) to the accompanying family
member only. Most were open to using new plasma biomarkers such as
pTau isoforms (64%), validated algorithms on-line to obtain a
probability score on the etiology of cognitive decline (58%) and
validated cognitive tests performed remotely (67%). The major
challenges they foresaw in the diagnosis of dementia are the growing
needs due to population ageing and availability of new disease
modifying therapies.
Conclusions
Neurologists around the world have contributed significantly to
acquire important knowledge about needs for current and future
diagnosis of dementia and are open to the use of new on-line resources
as well as plasma biomarkers as a complement to their usual clinical
assessment.
doi:10.1016/j.jns.2023.121394
121395
Steroid-responsive encephalopathy associated with autoimmune
thyroiditis
T.L.N. Geethaa, Azma Mohammedb, N.V. Sundaracharyb, aGuntur
Medical College, Department of Neurology, Guntur, India, bGovernment
General Hospital, Neurology, Guntur, India
Background and aims
Steroid-Responsive Encephalopathy Associated with Autoimmune
Thyroiditis (SREAT), or Hashimoto's Encephalopathy, is a rare and
underdiagnosed condition characterized by encephalopathy in the
presence of autoimmune thyroid disease. Aims: This case report aims
to increase awareness of SREAT and its management by presenting a
detailed case of a 75-year-old male with progressive cognitive decline,
behavioral abnormalities, and neurological findings.
Methods
This case report presents a 75-year-old male veterinary assistant who
experienced progressive memory disturbances and behavioral
abnormalities over a three-month period.
Results
Based on the clinical presentation, laboratory results, and
neuroimaging findings, the patient was diagnosed with Steroid-
Responsive Encephalopathy Associated with Autoimmune Thyroiditis
(SREAT). The treatment plan involved initiating pulse-dose
methylprednisolone (1 g/day for five days) followed by oral
prednisolone (40 mg/day), in addition to thyroxine replacement
therapy. A gradual tapering of steroids over a period of six weeks was
planned. The patient demonstrated significant improvement in
cognitive function, behavior, and mood within one week of initiating
treatment. He became more alert, regained the ability to recognize
relatives, and showed improved interest in his surroundings. Sleep-
related behavioral abnormalities resolved, and visuospatial orientation
improved.
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95
Conclusions
This case report highlights the importance of considering Steroid-
Responsive Encephalopathy Associated with Autoimmune Thyroiditis
(SREAT) as a potential diagnosis in patients presenting with
encephalopathy, particularly those with high anti-thyroid peroxidase
antibody titers. Prompt diagnosis and initiation of glucocorticoid
therapy, along with thyroxine replacement, can lead to significant
clinical improvement in cognitive function, behavior, and mood.
doi:10.1016/j.jns.2023.121395
121396
Brain-derived tau in blood as a biomarker for Alzheimer's disease-
type neurodegeneration
Fernando Gonzalez-Ortiza, Thomas Karikarib, Henrik Zetterberga, Kaj
Blennowa, aGothenburg University, Sahlgrenska University Hospital,
Mölndal, Sweden, bGothenburg University, Sahlgrenska University Hospital,
Mölndaln, Sweden
Background and aims
Blood-based biomarkers for amyloid-beta (Aꞵ) and phosphorylated-
tau (p-tau) show good diagnostic accuracies and agreements with their
corresponding cerebrospinal fluid (CSF) biomarkers in the amyloid/tau/
neurodegeneration (AT(N)) framework for Alzheimer's disease (AD).
However, the blood-based neurodegeneration marker neurofilament
light (NfL) is not specific to AD while t-tau shows no correlation with
CSF t-tau. Recent studies suggest that blood t-tau originates principally
from peripheral, non-brain sources.
Methods
We generated an anti-tau antibody that selectively binds brain-
derived tau (BD-tau) and avoids the peripherally-expressed “big tau”
isoform. We develop an ultrasensitive blood-based assay for BD-tau, and
validated it in five independent cohorts (n = 609) from various settings
including a blood-to-autopsy cohort, CSF biomarker-classified AD and
controls, and memory clinic cohorts.
Results
In paired samples, serum and CSF BD-tau were significantly correlated,
while serum and CSF t-tau were not. Blood-based BD-tau showed
equivalent diagnostic performance as CSF t-tau and CSF BD-tau to separate
biomarker-positive AD participants from biomarker-negative controls.
Plasma BD-tau accurately distinguished neuropathologically-confirmed
AD from non-AD controls while NfL did not. These performances were
independent of the presence of concomitant pathologies. Plasma BD-tau,
but not NfL, was associated with global and regional amyloid-plaque and
neurofibrillary-tangle counts. These results were further verified in two
memory clinic cohorts where BD-tau correlated with NfL in AD but not in
non-AD neurodegenerative disorders.
Conclusions
BD-tau is a novel blood-based biomarker that outperforms plasma t-tau
and, unlike NfL, shows specificity to AD-type neurodegeneration. BD-tau
completes the AT(N) scheme in blood, and will be useful to evaluate AD-
dependent neurodegenerative processes for clinical and research purposes.
doi:10.1016/j.jns.2023.121396