NACC分数是一种用于评估老年痴呆症的常用工具。它由美国老年痴呆症协会（NACC）

开发，旨在帮助医生和研究人员评估患者的认知功能和日常生活能力。
如何计算NACC分数？
NACC分数由两部分组成：认知总分和日常生活能力总分。认知总分包括记忆、语言、
注意力、执行功能和视觉空间能力等方面的评估。日常生活能力总分则包括独立生
活能力、日常活动能力和社会功能等方面的评估。医生可以通过对患者进行测试和
观察，来评估其在每个方面的表现，并最终得出NACC分数。
为什么要关注NACC分数？
NACC分数可以帮助医生和研究人员更准确地评估老年痴呆症患者的病情和病程。它
可以帮助医生制定个性化的治疗方案，提高患者的生活质量。同时，研究人员也可以
通过NACC 分数来比较不同治疗方法的有效性，从而推动老年痴呆症的治疗和研究。
如何提高NACC分数？
虽然老年痴呆症目前还没有有效的治愈方法，但是通过一些方法可以帮助提高患者的
NACC分数。例如，保持良好的生活习惯、参加认知训练、进行物理锻炼等，都可以帮
助改善患者的认知功能和日常生活能力。
在HelpWriting.net上订购NACC分数评估
如果您或您的家人被诊断为老年痴呆症，或者您是一位研究人员，想要进行老年痴
呆症相关的研究，我们推荐您在HelpWriting.net上订购NACC分数评估。HelpWriting.net是
一个专业的医学论文写作平台，拥有经验丰富的医学专家团队，可以为您提供高质
量的NACC 分数评估服务。让我们一起为老年痴呆症患者的治疗和研究贡献一份力量
吧！
Copyright © Queen’s Printer and Controller of HMSO 2021. This work was produced by Richardson
et al. under the terms of a commissioning contract issued by the Secretary of State for Health and
Social Care. This issue may be freely reproduced for the purposes of private research and study and
extracts (or indeed, the full report) may be included in professional journals provided that suitable
acknowledgement is made and the reproduction is not associated with any form of advertising.
Applications for commercial reproduction should be addressed to: NIHR Journals Library, National
Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House,
University of Southampton Science Park, Southampton SO16 7NS, UK. Frailty is a dementia risk
factor commonly measured by a frailty index (FI). The standard procedure for creating an FI requires
manually selecting health deficit items and lacks criteria for selection optimization. We hypothesized
that refining the item selection using data-driven assessment improves sensitivity to cognitive status
and future dementia conversion, and compared the predictive value of three FIs: a standard 93-item
FI was created after selecting health deficit items according to standard criteria (FI s ) from the
ADNI database. A refined FI (FI r ) was calculated by using a subset of items, identified using factor
analysis of mixed data (FAMD)-based cluster analysis. We developed both FIs for the ADNI1 cohort
( n = 819). We also calculated another standard FI (FI c ) developed by Canevelli and coworkers.
Results were validated in an external sample by pooling ADNI2 and ADNI-GO cohorts ( n = 815).
Cluster analysis yielded two clusters of subjects, which significantly (p FDR
<
.05)
differed
on
26
health
items,
which
were
used
to
compute
FI
r
.
The
data-
driven
subset
of
items
included
in
FI
r
covered
a
range
of
systems
and
included
well-
known
frailty
components,
e.g.,
gait
alterations
and
low
energy.
In
prediction
analyses,
FI
r
outperformed
FI
s
and
FI
c
in
terms
of
baseline
cognition
and
future
dementia
conversion
in
the
training
and
validation
cohorts.
In
conclusion,
the
data
show
that
data-
driven
health
deficit
assessment
improves
an
FI's
prediction
of
current
cognitive
status
and
future
dementia,
and
suggest
that
the
standard
FI
procedure
needs
to
be
refined
when
used
for
dementia
risk
assessment
purposes.
Bruce
Miller—receives
research
support
from
NIH.
Education
is
one
of
the
most
important
service-
oriented
sectors
with
a
significant
number
of
clients.
In
India,
the
population
of
students
pursuing
higher
education
is
enormous,
and
the
number
of
Higher
education
institutes
(HEI)
is
significantly
higher,
resulting
in
fierce
competition
among
HEIs.
The
sustainability
of
private
HEIs
has
become
extremely
difficult
due
to
intense
competition.
Their
survival
is
mainly
determined
by
the
number
of
students
enrolled
each
year.
To
combat
competition
and
increase
enrolments,
institutions
must
enhance
the
elements
influencing
college
choice
decisions
by
students.
This
study
employs
a
two-
phased
strategy
to
understand
the
perceptions
of
both
stakeholders
and
administrators.
The
Best–Worst
method
(BWM)
is
used
in
the
first
phase,
followed
by
the
Two-
Way
assessment
technique
in
the
second
phase.
Results
are
validated
using
real-
life
data
sets
collected
from
the
HEIs
in
Delhi
NCR.
The
research
results
show
that
out
of
nine
factors,
Placement,
tuition
fee
and
travelling
time,
distance
and
boarding
facility
are
the
top
priority
for
college
choice
admissions.
A
Marquis
Media
Company
Association
between
changing
hypnotic
use
status
between
previous
and
current
visit
on
depression
(measured
by
GDS,
higher
scores
represent
more
depressive
symptoms)
scores
at
previous
and
current
visit
(a–c).
Mean
scores
stratified
by
current
hypnotic
use,
with
inverse
probability
weights
used
to
account
for
differences
in
prior
predictors
of
hypnotic
use
(d–f).
(a)
Z-
drug;
(b)
BZD;
and
(c)
antipsychotics.
Data
from
the
NACC
data
set.
Background:
Neuropsychiatric
symptoms
cause
significant
suffering
and
poor
quality
of
life
for
patients
and
their
caregivers.
They
are
not
considered
specific
to
frontotemporal
dementia
(FTD);
therefore,
their
clinical
role
and
impact
might
be
underestimated.
Objective:
The
aims
of
the
present
study
are
to:
1)
describe
the
prevalence
of
neuropsychiatric
symptoms
in
FTD
starting
from
the
prodromal
stage,
2)
define
their
association
with
disease
severity,
3)
identify
symptoms
which
are
unrelated
to
FTD-
specific
symptoms,
and
4)
assess
their
association
with
clinical
features
and
outcomes.
Results:
In
this
retrospective
study,
we
analyzed
data
of
461
FTD
patients,
including
behavioral
variant
of
FTD
(bvFTD,
n
=
318)
and
primary
progressive
aphasia
(PPA,
n
=
143).
Neuropsychiatric
symptoms
were
assessed
using
the
Neuropsychiatric
Inventory,
and
patients’
staging
and
global
disease
severity
were
estimated
using
the
Clinical
Dementia
Rating
plus
NACC
FTLD.
Results:
The
most
common
neuropsychiatric
symptoms
in
prodromal
FTD
were
irritability
(48%),
depression
(35%),
and
anxiety
(34%);
delusions
were
reported
in
6%of
prodromal
bvFTD
cases.
The
severity
of
most
neuropsychiatric
symptoms
increased
with
global
disease
severity.
Psychosis
(delusions
and
hallucinations)
and
mood
symptoms
(depression
and
anxiety)
were
mostly
independent
from
FTD-
specific
symptoms.
Psychosis
was
associated
with
older
age,
higher
disease
severity,
shorter
survival
rate,
and
was
higher
in
bvFTD
than
in
PPA.
Conclusions:
Neuropsychiatric
symptoms
are
common
in
patients
with
FTD,
also
in
the
prodromal
phase.
Psychosis
might
be
unrelated
to
FTD
pathology,
and
be
associated
with
worse
clinical
outcomes.
The
prompt
detection
and
treatment
of
these
symptoms
might
improve
patient’s
management
and
quality
of
life.
...
Neuropsychiatric
symptoms
such
as
delusions,
hallucinations,
anxiety,
and
depression
are
considered
not
specific
to
FTD,
even
though
recent
studies
suggest
that
they
are
relatively
frequent
in
this
patient
population
[6][7][8],
have
different
trajectories
through
the
disease
course
[9],
and
cause
significant
suffering
and
poor
quality
of
life
for
both
the
patients
[10,11]
and
their
caregivers
[11].
Therefore,
the
early
detection
and
treatment
of
these
symptoms
might
have
relevant
implications
for
the
management
and
quality
of
life
of
FTD
patients
and
their
caregivers.
...
Walter
Kukull—receives
research
support
from
NIH.
Reporting open: This review describes associations between dementia and loneliness on the
neurobiological and epidemiological levels according to the recent body of literature. The aim of this
study
was
to
highlight major lines of research in this field. Sociocognitive skills and social interactions present
complex interdependencies with dementia which may be explained by two theories. According to
the
first
one, not sufficiently engaging in social or cognitive activities results in brain atrophy. The second
one
claims that brain neurogenesis and synaptic density are being increased by social connections. The
relationship between loneliness and dementia could be mediated by sensory loss, including hearing
and
visual impairment, as well as depression and psychotic symptoms. Loneliness itself might cause a
depletion in sensory and cognitive stimulation which results in a decrease in neural reserve. Certain
changes in the structures of the brain caused by loneliness were found in imaging examination.
Loneliness appears to be a crucial risk factor for dementia in recent times due to the modern lifestyle
and
consequences of the outbreak of COVID-19. Additional studies are required to understand more
completely the key tenets of this topic and therefore to improve the prevention and treatment of
dementia. (a) Distribution of CDR-SOB with respect to dementia severity; (b) distribution of CDR-
SOB with respect to Z-drug use; (c) mean score over NACC visit, stratified by age group; and (d)
mean score over NACC visit, stratified by number of visits completed. ... Furthermore, a prospective
study
embedded within 7,439 U.S. community-dwelling older adults showed that frail individuals had
lower level (-0.03SD/ year, 95%CI: -0.04, -0.01) and steeper decline (-0.01SD/ year, 95%CI: -0.012,
-0.005) in global cognitive function than the robust [8]. In addition, a longitudinal study incorporated
14,490 participants aged 50 years and older from the National Alzheimer's Coordinating Centre
found that per 0.1 increment in FI was associated with elevated risk of developing MCI [HR
(95%CI) = 1.66 (1.55, 1.78)] [36]. In this study, we incorporated both frailty measures: FI and
dichotomised frailty status, which allows our results to be compared across a wider range of related
studies. ... Average NAcc responses for each subtype in anticipation period (a) and outcome period
(b)
with
standard
errors of mean. ... GSH is used for the reduction of ROS via glutathione peroxidase (GPX) and the
resulting
glutathione disulfide (GSSG) can be converted back to GSH via glutathione reductase (GR). NAC
has
been a target of interest primarily for its antioxidative role in a variety of disorders including neural
cell survival, cell signaling, neurodegenerative diseases, multiple sclerosis, traumatic brain injuries,
and
other psychotic disorders [24,25]. Its antioxidant effects can be extrapolated to play a role in the
redox balance in ASD. ... The scoring rules for determining the global CDR plus NACC FTLD score
support@naccchart.com Interpretation: The global scoring system we created for the CDR plus
NACC
FTLD is valuable for use in persons with FTLD syndromes. ... Since the result indicated that cGLM
is
preferred for RTP, the simulated RTP system implemented cGLM. We used this system for the RTP
simulation with resting-state fMRI data and rtfMRI neurofeedback task data targeting the left
amygdala activation (LA-NF) [26]. To evaluate RTP's benefit in noise reduction, we calculated the
amounts of variance explained by the motion and physiological noises in the real-time estimate. ...
Bradford Dickerson—receives research support from NIH. Future directions: The manuscript
proposes a framework for detecting early clinical changes of the FTLD spectrum diseases. Further
studies
to
address the utility of the CDR plus NACC FTLD should include: (a) longitudinal data showing
detection
capability of clinical decline or improvement, (b) optimizing the combination of neuropsychological
batteries with the CDR plus NACC FTLD, and (c) correlation with biofluid and/or neuroimaging
biomarkers. Walter Kremers—receives research funding from AstraZeneca, Biogen, Roche, DOD,
and
NIH.
Published in Archives of Neurology 2010 Background Frailty indicators can operate in dynamic
amalgamations of disease conditions, clinical symptoms, biomarkers, medical signals, cognitive
characteristics, and even health beliefs and practices. This study is the first to evaluate which, among
these
multiple frailty-related indicators, are important and differential predictors of clinical cohorts that
represent
progression along an Alzheimer’s disease (AD) spectrum. We applied machine-learning technology
to
such
indicators in order to identify the leading predictors of three AD spectrum cohorts; viz., subjective
cognitive
impairment (SCI), mild cognitive impairment (MCI), and AD. The common benchmark was a cohort
of
cognitively unimpaired (CU) older adults. Methods The four cohorts were from the cross-sectional
Comprehensive Assessment of Neurodegeneration and Dementia dataset. We used random forest
analysis (Python 3.7) to simultaneously test the relative importance of 83 multi-modal frailty
indicators in discriminating the cohorts. We performed an explainable artificial intelligence method
(Tree Shapley Additive exPlanation values) for deep interpretation of prediction effects. Results We
observed strong concurrent prediction results, with clusters varying across cohorts. The SCI model
demonstrated excellent prediction accuracy (AUC = 0.89). Three leading predictors were poorer
quality
of
life
([QoL]; memory), abnormal lymphocyte count, and abnormal neutrophil count. The MCI model
demonstrated a similarly high AUC (0.88). Five leading predictors were poorer QoL (memory,
leisure), male sex, abnormal lymphocyte count, and poorer self-rated eyesight. The AD model
demonstrated outstanding prediction accuracy (AUC = 0.98). Ten leading predictors were poorer
QoL (memory), reduced olfaction, male sex, increased dependence in activities of daily living (n =
6), and poorer visual contrast. Conclusions Both convergent and cohort-specific frailty factors
discriminated the AD spectrum cohorts. Convergence was observed as all cohorts were marked by
lower quality of life (memory), supporting recent research and clinical attention to subjective
experiences of memory aging and their potentially broad ramifications. Diversity was displayed in
that, of the 14 leading predictors extracted across models, 11 were selectively sensitive to one
cohort. A morbidity intensity trend was indicated by an increasing number and diversity of predictors
corresponding to clinical severity, especially in AD. Knowledge of differential deficit predictors
across AD clinical cohorts may promote precision interventions. Sort by Citation Count Anti-
Ragging policy is strictly implemented in this institution. Based on the Guidelines of the UGC and
the
directions of the Hon’ble Supreme Court of India, all the steps and precautions to prevent ragging is
effected in our institutions. Any student studying or seeking admission should not involve or indulge
in
any sort of ragging in the campus, hostels or elsewhere. Ragging in any manner is a criminal offense
and
strictly policed & prohibited. Students found guilty of involving in ragging will be subjected to
severe punishment as offence under IPC leading to expulsion from the institute without any notice.
The
course
of
action for the students proven guilty in ragging will be as per the rules and regulations on prevention
of
ragging imposed from time to time by the Government / Apex Courts or any other competent
authorities. Features © 2008-2024 ResearchGate GmbH. All rights reserved. ... Additionally,
increased
spine densities in the NAc core and shell following cocaine administration are correlated with
increased
preference to be in the location with which cocaine is commonly paired (i.e. cocaine-induced place
preference; Marie et al. 2012). These results suggest that cocaineinduced changes in MSNs regulate
approach to contextual cues commonly paired with the US effects of cocaine. ...
Go
to
this
page
to
see
a
list
of
supported
browsers
Hilary
W.
Heuer—receives
research
support
from
NIH.
Julie
Fields—receives
research
support
from
NIH.
Longitudinal
change
in
depression
and
anxiety
in
asymptomatic
(CDR
plus
NACC
FTLD
global
score
of
0),
prodromal
(0.5)
and
symptomatic
(≥1)
mutation
carriers:
(A)
mean
severity
of
depression
(solid
line)
and
anxiety
(dotted
line)
within
all
carriers;
(B,
C)
Sankey
diagrams
showing
individual
change
in
depression
(B)
and
anxiety
(C)
scores.
CDR,
Clinical
Dementia
Rating;
NACC
FTLD,
National
Alzheimer's
Coordinating
Center
Behaviour
and
Language
Domains.
Andhra
Pradesh
-
531
001
John
Q.
Trojanowski—may
accrue
revenue
in
the
future
on
patents
submitted
by
the
University
of
Pennsylvania
wherein
he
is
coinventor
and
he
received
revenue
from
the
sale
of
Avid
to
Eli
Lily
as
coinventor
on
Aβ
amyloid
imaging-
related
patents
submitted
by
the
University
of
Pennsylvania.
He
receives
research
support
from
the
NIH
and
several
nonprofits.
Anakapalle,
Visakhapatnam
Dist.,
...
Light
fixation
of
brains
with
PFA
was
performed
as
previously
described
(Kim
et
al.,
2007;Marie
et
al.,
2012).
Briefly,
following
anesthesia,
tissues
were
fixed
with
intracardiac
perfusion
with
ice-
cold
1.5%
PFA
in
0.1
M
phosphate
buffer
for
15
minutes
with
a
peristaltic
pump
fixed
at
20
mL/
min.
...
Toji
Miyagawa—receives
research
support
from
the
Japanese
Society
of
Neurology,
SENSHIN
Medical
Research
Foundation,
and
Mitsukoshi
Health
and
Welfare
Foundation.
Association
between
changing
hypnotic
use
status
between
previous
and
current
visit
on
depression
(measured
by
GDS,
higher
scores
represent
more
depressive
symptoms)
scores
at
previous
and
current
visit
(a–c).
Mean
scores
stratified
by
current
hypnotic
use,
with
inverse
probability
weights
used
to
account
for
differences
in
prior
predictors
of
hypnotic
use
(d–f).
(a)
Z-
drug;
(b)
BZD;
and
(c)
antipsychotics.
Data
from
the
NACC
data
set.
Frontotemporal
dementia
(FTD)
is
one
of
the
most
common
causes
of
early
onset
dementia
and
an
umbrella
term
for
three
clinical
syndromes
which
present
with
behavioral/
social
disturbance
and/
or
language
impairment:
behavioral
variant
FTD
(bvFTD),
semantic
variant
primary
progressive
aphasia
(svPPA),
and
non-
fluent/
agrammatic
variant
PPA
(nfvPPA).
The
term
frontotemporal
lobar
degeneration
(FTLD)
is
usually
used
to
represent
neuropathological
diagnoses
associated
with
neurodegeneration
of
the
frontal
and
temporal
lobes
caused
typically
by
aberrant
accumulation
of
tau
or
TAR
DNA
binding
protein
(TDP-
43).
FTLD
spectrum
disorders
include
three
subtypes
of
FTDs
(bvFTD/
svPPA/
nfvPPA),
progressive
supranuclear
palsy/
Richardson's
syndrome
(PSP-
RS),
corticobasal
syndrome
(CBS),
and
FTD
with
amyotrophic lateral sclerosis (FTD-ALS). Some clinical phenotypes of FTLD spectrum disorders are
associated
with
specific proteins; nfvPPA is most often associated with FTLD-tau and svPPA with FTLD-TDP. Each
FTD
subtype and other FTLD spectrum disorders present discriminative and unique clinical characteristics
depending on the anatomical area affected, but these FTLD spectrum disorders share many
characteristics that are different from Alzheimer's disease dementia (AD), with behavioral/social
disturbance
and/
or
language
impairment being predominant and memory (MEM) and orientation (ORI) being relatively preserved
in
the
early
phase. The number of participants continuing, stopping or starting Z-drugs, BZDs or antipsychotics
between
NACC
visits The CDR global rating of 0 = normal cognition/function was seen in > 25% of the MCI-beh,
MCI-cog, and nfvPPA participants despite their diagnoses. We previously reported that the mild
nfvPPA participants in the ARTFL/LEFFTDS Consortium study tended to have less frequent
impairment on the six domains of the CDR, resulting in difficulty in detecting clinical features by the
CDR.7 With the CDR plus NACC FTLD and the global scoring rules we developed, we were able
to
detect clinical impairment in all of the MCI-beh, MCI-cog, and FTD cases who had a global CDR
score
of
0. There was a higher frequency of a global rating of 3 = severe impairment seen in the bvFTD
participants than in the svPPA and the nfvPPA participants. One of the reasons for this result might
be that, although the ARTFL/LEFFTDS Consortium study targeted the mild phase of FTLD,
severely impaired FTD participants were sometimes registered in the study to co-register other
preclinical members of kindreds of the familial FTD. For this purpose, the bvFTD participants were
more
likely to have known FTLD-related gene mutations and to be enrolled in the study even if they were
severely impaired and untestable. Indeed, all of the bvFTD participants with the global CDR plus
NACC
FTLD
score
of
3 and who were rated on the FAQ had FAQ scores of 25 or more, which indicated severe functional
impairment. Background and Hypothesis Clinical high risk for psychosis (CHR-P) offers a window
of
opportunity for early intervention and recent trials have shown promising results for the use of N-
acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention
(IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of
CHR-P patients. Study Design In this double-blind, randomized, controlled multicenter trial, a 2 × 2
factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI
compared to psychological stress management (PSM). The primary endpoint was the transition to
psychosis or deterioration of CHR-P symptoms after 18 months. Study Results While insufficient
recruitment led to early trial termination, a total of 48 participants were included in the study.
Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI
+ NAC: 72.7 ± 13.4%, PSM + NAC: 72.7 ± 13.4%) as compared to patients receiving PLC (IPPI +
PLC: 56.1 ± 15.3%, PSM + PLC: 39.0 ± 17.4%). However, a log-rank chi-square test in
Kaplan–Meier analysis revealed no significant difference of survival probability for NAC vs control
(point hazard ratio: 0.879, 95% CI 0.281–2.756) or IPPI vs control (point hazard ratio: 0.827, 95%
CI 0.295–2.314). The number of adverse events (AE) did not differ significantly between the four
groups. Conclusions The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P
compared to controls could not be statistically validated in this trial. However, results indicate a
consistent pattern that warrants further testing of NAC as a promising and well-tolerated
intervention for CHR patients in future trials with adequate statistical power. Copyright © 2019. All
Rights Reserved. As demonstrated with our analysis, the CDR was not sensitive in detecting early
symptomatology of FTLD. The CDR was originally developed for assessing global functions and
cognition on AD dementia patients. While there were domains for MEM impairment and
disorientation typically seen in AD patients, there were no domains on behavioral disturbances or
language
impairment. Furthermore, the six domains of the CDR were not weighed equally in determining the
global
CDR score; the MEM domain was designated as the primary domain and the other five domains as
secondary. If only one domain, other than the MEM domain, is rated > 0, global CDR is calculated
to
be 0. In developing the scoring rules for the global CDR plus NACC FTLD rating, eight domains,
including the BEHAV and LANG domains, were weighted equally to determine the global score,
and
the
global
CDR plus NACC FTLD score will become > 0 if any of the eight domains were rated as > 0. Maria
C. Tartaglia—nothing to disclose. Edward Huey—receives research support from NIH.
www.marquis-media.com Jill S. Goldman—is serving as a consultant to the Novartis Alzheimer's
Prevention Advisory Board. She receives research support from NIH, HDSA, New York State
Department of Health (RFA # 1510130358). CONTACT ADDRESS ... controlled and uncontrolled
trials were conducted on various impulse control disorders including trichotillomania, skin picking
disorder and nail biting disorder (Table 13). ... The battle for NACC’s most-added album this week
was
a
nail biter between CHAI and Slaughter Beach, Dog. In the end, only one Top 10 Add separated the
two. And it was Slaughter Beach, Dog that came out on top with 59 Top 10 Adds. Initially begun in
2014 as a solo project for Modern Baseball co-frontman Jake Ewald, the band became a full-fledged
band and has enjoyed great success on the NACC 200 with their previous two albums reaching the
NACC
Top 10. Crying, Laughing, Waving, Smiling (Lame-O) is the band’s fifth LP and their second to take
‘most-added’ honors. Bradford Dickerson—receives research support from NIH. Copyright © 1999-
2024 John Wiley & Sons, Inc or related companies. All rights reserved, including rights for text and
data
mining and training of artificial technologies or similar technologies. Scott McGinnis—has served as
an
investigator for clinical trials sponsored by AbbVie, Allon Therapeutics, Biogen, Bristol-Myers
Squibb, C2N Diagnostics, Eisai Inc., Eli Lilly and Co., Genentech, Janssen Pharmaceuticals,
Medivation, Merck, Navidea Biopharmaceuticals, Novartis, Pfizer, and TauRx Therapeutics. He
receives
research
support
from
NIH.
...
analysis was performed only for the MDD subjects since there were no or very small variances in
these symptom scores for the HC group. Supplementary Fig. S3 shows the history of recursive
feature elimination and the distribution of the dis- criminant scores in the extraction of symptom
items associated with the NAcc subtypes (See Methods for detailed procedure). The best
classification score with a leave-one-out cross-validation was achieved with a set of 25 variables for
the
left and with nine variables for the right NAcc subtypes. ... Table 3 demonstrates the interrater
reliability study regarding two sites and 40 study participants, and the ratings for each case for each
of
the
sites are shown in the supporting information. Most participants were middle aged, and all were
white with nearly equal sex ratio and at least 12 years of education. All participants with the
diagnoses
of
CN, MCI-beh, and MCI-cog were members of familial FTD with either MAPT, c9orf72, or GRN
mutations. Twenty participants (50%) were CN; nine participants (22.5%) were either MCI-beh or
MCI-cog; eleven participants (27.5%) were diagnosed as FTD, ALS, or AD. Interrater reliability of
global
CDR plus NACC FTLD scores assessed by weighted kappa statistic was very good (weighted κ =
0.84 [95% confidence interval (CI) 0.72–0.96]) and comparable to the global CDR scores (weighted
κ = 0.84 [95% CI 0.72–0.97]). Interrater reliability of the CDR plus NACC FTLD-SB assessed by
ICC was also very good (ICC = 0.95 [95% CI 0.87–0.98]) and comparable to the CDR-SB (ICC =
0.95 [95% CI 0.86–0.98]).
N-acetylcysteine is a precursor to L-cysteine, which in turn is a component of the endogenous
antioxidant glutathione, which is a tripeptide composed of glutamate, cysteine and glycine. The
objective of this review is to carry out a broad and exhaustive analysis of the available scientific
evidence on the role of N-acetylcysteine in the treatment of neurodegenerative diseases. The
administration of NAC was analyzed in patients with Alzheimer's disease, Parkinson's disease and
multiple sclerosis. In conclusion, comment that the intake of N-acetylcysteine has beneficial effects
on neurotransmission, oxidative stress, γ-secretase activity, letter fluency, immediate memory of
numbers, memory, the dopaminergic system, glutathione brain, malondialdehyde levels, anxiety,
brain glucose levels, cognition and attention. Bradford Dickerson—receives research support from
NIH. ... Although frailty and dementia are inter-related, they are distinct concepts and by including
dementia-related measures (e.g., certain activities of daily living, cognitive test results) into an FI, its
use in the prediction of dementia may become circular. While Ward and coworkers found a
significant association between FI and future dementia risk when adjusting for global cognition [12],
results across studies show, however, that the association between FIs and future dementia risk
weakens after removing deficits which might represent early core dementia symptoms [6,12]. How
to construct an optimal FI for dementia risk prediction purposes remains unknown. ... Anhedonia or
inability to experience pleasure is the sign of various neuropsychiatric conditions. Current treatment
options do not provide adequate control of anhedonia. The present study was conducted to evaluate
the protective effects of valproic acid (VPA) as a nonspecific histone deacetylase (HDAC) inhibitor
to reverse the effects of stress on induction of anhedonia and explore possible mechanisms. To
induce anhedonia, a rat model of chronic unpredictable mild stress (CUMS) was established.
Animals were assigned into no stress, stress (6 weeks of CUMS) and two treatment groups. VPA
treatment was carried out for 4 continuous weeks (200 mg/kg/day). Behavioral assessments were
performed using sucrose consumption (SCT) and new object recognition (NOR) tests. The
expression of genes was evaluated using qRT-PCR. The cell density was determined using Nissl
staining. Rats with CUMS showed depressive-like behaviors and impaired memory performance
compared with the non-stressed group (p < 0.01). Moreover, they had significantly higher levels of
HDAC3 and MC4R expression in the nucleus accumbens (NAc) compared to the non-stressed group
(p < 0.01). The NAc cell density was significantly higher in the non-stressed rats (p < 0.05).
Corticosterone plasma level was increased in the CUMS compared to the non-stressed group (p <
0.05). In the CUMS + VPA subgroup, the corticosterone (CORT) plasma level was lower compared
with the CUMS + Saline and/or the CUMS groups (p
<
0.05).
These
findings
suggest
that
VPA
can
improve
anhedonia
and
stress.
Although
the
protective
effect
of
VPA
might
link
to
decreasing
HDAC3
and
MC4R
genes
expression
in
NAc.
Association
between
changing
hypnotic
use
status
between
previous
and
current
visit
on
depression
(measured
by
GDS,
higher
scores
represent
more
depressive
symptoms)
scores
at
previous
and
current
visit
(a–c).
Mean
scores
stratified
by
current
hypnotic
use,
with
inverse
probability
weights
used
to
account
for
differences
in
prior
predictors
of
hypnotic
use
(d–f).
(a)
Z-
drug;
(b)
BZD;
and
(c)
antipsychotics.
Data
from
the
NACC
data
set.
...
provides
multiple
measures
of
cognitive
state,
in
addition
to
MMSE
and
MOCA.
The
cognitive
scores
typically
align
with
the
objective
diagnoses
or
functional
norm,
but
not
absolutely
(
Figure
6C).
An
assessment
by
a
trained
clinician
is
decisive
and
such
scores
are
NACCNORM
(clinical
norm
during
all
visits)
and
NACCUSDS
(1
-
norm,
2
-
pre-
MCI,
3
-
MCI,
4-
dementia).
...
Copyright
©
2019.
All
Rights
Reserved.
The
number
of
participants
continuing,
stopping
or
starting
Z-
drugs,
BZDs
or
antipsychotics
between
NACC
visits
SUBSCRIBE
to
NACC
to
view
the
full
top
30
charts
in
all
genres.
Your
eyes
don’t
have
to
be
the
only
way
you
experience
NACC’s
musical
highlights.
Follow
the
‘College
Radio
Weekly
Highlights’
playlist
on
Spotify
and
let
your
ears
in
on
the
action
too.
Patrick
Brannelly—employed
by
the
Rainwater
Charitable
Foundation.
We
extend
our
appreciation
to
Drs.
John
Hsiao
and
Dallas
Anderson
from
the
National
Institute
on
Aging,
Drs.
Marg
Sutherland
and
Codrin
Lungu
from
the
National
Institute
of
Neurological
Disorders
and
Stroke,
the
staff
of
all
centers,
and
particularly
our
patients
and
their
families
for
their
participation
in
the
ARTFL
and
LEFFTDS
protocols.
Kelley
Faber—receives
research
support
from
NIH.
Neill
Graff-
Radford—receives
royalties
from
UpToDate,
and
has
participated
in
multicenter
therapy
studies
by
sponsored
by
Biogen,
TauRx,
AbbVie,
Novartis,
and
Lilly.
He
receives
research
support
from
NIH.
...
NAC
(Figure
1)
is
considered
a
safe
and
well
tolerated
medication
that
has
been
used
worldwide
in
a
variety
of
medical
conditions
over
the
past
decades
[1].
Over
the
past
decade,
there
has
been
increasing
interest
in
the
use
of
NAC
to
treat
psychiatric
and
neurological
disorders
[1].
...
The
developed
scoring
rules
for
the
global
CDR
plus
NACC
FTLD
score
calculated
from
each
rating
of
the
eight
domains
of
CDR
plus
NACC
FTLD
are
shown
in
Figure 1.
Ratings
of
the
individual
eight
domains
were
determined
based
on
the
information
from
ADCS-
CGIC
semi-
structured
interviews
with
participants
and
their
informants
as
was
used
for
the
original
FTLD-
CDR
study.3,
5
Unlike
the
global
CDR
score
for
which
the
MEM
domain
is
regarded
as
the
primary
domain
and
the
others
secondary,
all
eight
domains
of
the
CDR
plus
NACC
FTLD
are
equally
weighted
in
calculating
the
global
CDR
plus
NACC
FTLD
score,
and
if
any
domain
has
rating
of
>
0,
the
global
CDR
plus
NACC
FTLD
score
is
at
least
0.5.
Better
functioning
nervous
system
stimulates
other
organs,
promoting
longevity.
As
a
trade-
off,
this
stimulation
may
result
in
enhanced
oncogenesis.
This
hypothesis
was
tested
by
analyzing
factors
reflecting
cognitive
score
and
academic performance, Educational performance emerged as a universal independent negative
correlate for most of comorbidit... Nupur Ghoshal—has participated in or is currently participating in
clinical trials of anti-dementia drugs sponsored by the following companies: Bristol Myers Squibb,
Eli Lilly/Avid Radiopharmaceuticals, Janssen Immunotherapy, Novartis, Pfizer, Wyeth, SNIFF (The
Study of Nasal Insulin to Fight Forgetfulness) study, and A4 (The Anti-Amyloid Treatment in
Asymptomatic Alzheimer's Disease) trial. She receives research support from Tau Consortium and
Association
for
Frontotemporal Dementia and is funded by the NIH. Join ResearchGate to find the people and
research
you
need to help your work ... The GENFI network has also developed several scale modules which
integrate the CDR Dementia Staging Instrument plus National Alzheimer's Coordinating Center
(NACC) Behavior and Language Domains (CDR plus NACC FTLD) [50], also known as FTLD-
CDR, to include neuropsychiatric [51] and motor symptoms [52]. Additionally, the revised version of
the
Cambridge Behavioural Inventory and the revised Self-Monitoring Scale have demonstrated
sensitivity to early behavioral alterations in genetic FTD, implying their potential utility in future
clinical trials [53][54][55]. ... Sort by Relevance Each study participant underwent neurological and
neuropsychological assessment according to the ARTFL/LEFFTDS Consortium study protocol.
Participants were evaluated using the Montreal Cognitive Assessment17 (lower score signifies more
impairment), Unified Parkinson's Disease Rating Scale18 (higher score signifies more motor
impairment), and Progressive Supranuclear Palsy Rating Scale19 (higher score signifies more motor
impairment). The Functional Activities Questionnaire20 (FAQ; higher score signifies more functional
impairment) and Neuropsychiatric Inventory Questionnaire21 (higher score signifies more
neuropsychiatric morbidity) were completed by interview with participants’ informants. Lead (Pb) is
a
heavy metal that can have harmful effects on the environment, which has severe cytotoxicity in many
animal tissues. N-acetylcysteine (NAC) has antioxidant activity, reducing lead-induced oxidative
stress and apoptosis, but its role in chicken cells is unknown. The current study explored the
antagonistic effect of NAC on lead-induced apoptosis and oxidative stress in chicken embryo
fibroblast (CEF). In this study, CEF was used as a model to measure the cytotoxic effects of lead
nitrate at different concentrations, demonstrating a dose-dependent effect on CEF activity.
Employing inverted microscopy, the investigation of morphological alterations in CEF cells was
conducted. Fluorescence staining methodology enabled the assessment of reactive oxygen species
(ROS) levels within CEF cells. Moreover, an enzyme-linked immunosorbent assay was utilized to
detect the presence of oxidative damage indicators encompassing superoxide dismutase (SOD),
glutathione peroxidase (GSH-Px), catalase (CAT) activity, malondialdehyde (MDA) content, and
total antioxidant capacity (T-AOC) within CEF cells. Furthermore, the determination of the
apoptosis rate of CEF cells was accomplished through the utilization of the Hoechst 33258 staining
method in combination with the Annexin V-FITC dual staining method. By using RT-qPCR for
detection, lead treatment increased expression of pro-apoptotic genes, caspase-3, and caspase-9, and
reduced expression of anti-apoptotic genes, Bcl-2, and BI-1. Reduced antioxidant capacity was
shown
by
increased ROS and MDA levels in CEF cells after lead treatment. The results showed that NAC
inhibited the expression of caspase-3 and caspase-9 in lead-treated CEF cells, while NAC had a
certain inhibitory effect on the relative expression of Bcl-2 and BI-1 mRNA in lead-induced CEF
cells. NAC significantly reduced lead-induced oxidative damage and apoptosis. Overall, our results
demonstrate a novel protective effect of NAC against lead-induced injury in chicken cells, providing
a
theoretical basis for future investigations of drugs that are effective in preventing lead poisoning in
animals. ... Reward process disturbance and dysfunction in regions within the reward-related network
were
also shown in MDD patients with SI symptoms (Misaki et al., 2016;Quevedo et al., 2017;Xie et al.,
2014). For example, MDD patients with SI failed to show any feedbackdependent caudate regulation
in
the
monetary incentive delay task (Xie et al., 2014). ... The frequency and distribution of global CDR
plus
NACC
FTLD
and
CDR
scores
of
the
diagnostic groups of MCI-beh, MCI-cog, and FTDs (bvFTD, svPPA, and nfvPPA) are shown in
Figure 2. All 970 participants were rated with both the CDR plus NACC FTLD and CDR. Among
the
FTDs, the bvFTD participants had the highest frequency of the maximum global rating (global score
of
3
= floor effects), 10% by CDR plus NACC FTLD and 5% by CDR. All bvFTD participants who
were
rated with a global CDR plus NACC FTLD score of 3 and were rated on the FAQ had FAQ scores
of
25 or more (max functional impairment: 30) and half of the participants were rated as 30. The
maximum global rating in the svPPA participants was seen in 1% by the CDR plus NACC FTLD and
0% by the CDR and maximum global rating in the nfvPPA participants was seen in 3% by both the
CDR
plus
NACC
FTLD
and
CDR. No MCI-beh or MCI-cog participant was rated as global score of 2 or 3 by CDR or CDR plus
NACC
FTLD. Despite their diagnoses of dementia or mild cognitive/behavioral impairment, 29% of the
MCI-beh, 23% of the MCI-cog, and 21% of the nfvPPA participants were rated normal (global score
of
0) by CDR. ... The current collection of factors represents standard frailty-related clusters, such as
disease syndromes, clinical symptoms, biomarkers, risk factors, medical signals, cognitive
characteristics, and health beliefs or practices [13]. Accumulating evidence indicates that progression
along fitness-frailty continua predicts an increased risk for exacerbated cognitive decline [71,72], as
well
as
SCI [2,3], MCI [4], and AD [5,6]. We are unaware of prior research that investigated the number and
profile of frailty factor signatures that optimize differential prediction of these prominent geriatric
conditions. ... Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has
been
diagnosed in an increasing number of children around the world. The existing data suggest that early
diagnosis and intervention can improve ASD outcomes. The causes of ASD remain complex and
unclear, and there are currently no clinical biomarkers for autism spectrum disorder. There is an
increasing
recognition that ASD might be associated with oxidative stress through several mechanisms
including abnormal metabolism (lipid peroxidation) and the toxic buildup of reactive oxygen species
(ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. This
open-label pilot study investigates the tolerability and effectiveness of oral supplementation with
OpitacTM gluthathione as a treatment for patients with ASD. The various aspects of glutathione
OpitacTM glutathione bioavailability were examined when administered by oral routes. The
absorption of glutathione from the gastrointestinal tract has been recently investigated. The results of
this
case series suggest that oral glutathione supplementation may improve oxidative markers, but this
does not necessarily translate to the observed clinical improvement of subjects with ASD. The study
reports a good safety profile of glutathione use, with stomach upset reported in four out of six
subjects. This article discusses the role of the gut microbiome and redox balance in ASD and notes
that
a
high baseline oxidative burden may make some patients poor responders to glutathione
supplementation. In conclusion, an imbalance in redox reactions is only one of the many factors
contributing to ASD, and further studies are necessary to investigate other factors, such as impaired
neurotransmission, immune dysregulation in the brain, and mitochondrial dysfunction. Phone: Maria
C. Tartaglia—nothing to disclose.
Jill
S.
Goldman—is
serving
as
a
consultant
to
the
Novartis
Alzheimer's
Prevention
Advisory
Board.
She
receives
research
support
from
NIH,
HDSA,
New
York
State
Department
of
Health
(RFA
#
1510130358).
Copyright
©
1999-
2024
John
Wiley
&
Sons,
Inc
or
related
companies.
All
rights
reserved,
including
rights
for
text
and
data
mining
and
training
of
artificial
technologies
or
similar
technologies.
David
Jones—receives
research
support
from
NIH
and
the
Minnesota
Partnership
for
Biotechnology
and
Medical
Genomics.
Support
Hours:
Content
may
be
subject
to
copyright.
Background
Efforts
to
develop
neuroimaging-
based
biomarkers
in
major
depressive
disorder
(MDD),
at
the
individual
level,
have
been
limited
to
date.
As
diagnostic
criteria
are
currently
symptom-
based,
MDD
is
conceptualized
as
a
disorder
rather
than
a
disease
with
a
known
etiology;
further,
neural
measures
are
often
confounded
by
medication
status
and
heterogeneous
symptom
states.
Methods
We
describe
a
consortium
to
quantify
neuroanatomical
and
neurofunctional
heterogeneity
via
the
dimensions
of
novel
multivariate
coordinate
system
(COORDINATE-
MDD).
Utilizing
imaging
harmonization
and
machine
learning
methods
in
a
large
cohort
of
medication-
free,
deeply
phenotyped
MDD
participants,
patterns
of
brain
alteration
are
defined
in
replicable
and
neurobiologically-
based
dimensions
and
offer
the
potential
to
predict
treatment
response
at
the
individual
level.
International
datasets
are
being
shared
from
multi-
ethnic
community
populations,
first
episode
and
recurrent
MDD,
which
are
medication-
free,
in
a
current
depressive
episode
with
prospective
longitudinal
treatment
outcomes
and
in
remission.
Neuroimaging
data
consist
of
de-
identified,
individual,
structural
MRI
and
resting-
state
functional
MRI
with
additional
positron
emission
tomography
(PET)
data
at
specific
sites.
State-
of-
the-
art
analytic
methods
include
automated
image
processing
for
extraction
of
anatomical
and
functional
imaging
variables,
statistical
harmonization
of
imaging
variables
to
account
for
site
and
scanner
variations,
and
semi-
supervised
machine
learning
methods
that
identify
dominant
patterns
associated
with
MDD
from
neural
structure
and
function
in
healthy
participants.
Results
We
are
applying
an
iterative
process
by
defining
the
neural
dimensions
that
characterise
deeply
phenotyped
samples
and
then
testing
the
dimensions
in
novel
samples
to
assess
specificity
and
reliability.
Crucially,
we
aim
to
use
machine
learning
methods
to
identify
novel
predictors
of
treatment
response
based
on
prospective
longitudinal
treatment
outcome
data,
and
we
can
externally
validate
the
dimensions
in
fully
independent
sites.
Conclusion
We
describe
the
consortium,
imaging
protocols
and
analytics
using
preliminary
results.
Our
findings
thus
far
demonstrate
how
datasets
across
many
sites
can
be
harmonized
and
constructively
pooled
to
enable
execution
of
this
large-
scale
project.
The
CDR
global
rating
of
0
=
normal
cognition/
function
was
seen
in
>
25%
of
the
MCI-
beh,
MCI-
cog,
and
nfvPPA
participants
despite
their
diagnoses.
We
previously
reported
that
the
mild
nfvPPA
participants
in
the
ARTFL/
LEFFTDS
Consortium
study
tended
to
have
less
frequent
impairment
on
the
six
domains
of
the
CDR,
resulting
in
difficulty
in
detecting
clinical
features
by
the
CDR.7
With
the
CDR
plus
NACC
FTLD
and
the
global
scoring
rules
we
developed,
we
were
able
to
detect
clinical
impairment
in
all
of
the
MCI-
beh,
MCI-
cog,
and
FTD
cases
who
had
a
global
CDR
score
of
0.
There
was
a
higher
frequency
of
a
global
rating
of
3
=
severe
impairment
seen
in
the
bvFTD
participants
than
in
the
svPPA
and
the
nfvPPA
participants.
One
of
the
reasons
for
this
result
might
be
that,
although
the
ARTFL/
LEFFTDS
Consortium
study
targeted
the
mild
phase
of
FTLD,
severely
impaired
FTD
participants
were
sometimes
registered
in
the
study
to
co-
register
other
preclinical
members
of
kindreds
of
the
familial
FTD.
For
this
purpose,
the
bvFTD
participants
were
more
likely
to
have
known
FTLD-
related
gene
mutations
and
to
be
enrolled
in
the
study
even
if
they
were
severely
impaired
and
untestable.
Indeed,
all
of
the
bvFTD
participants
with
the
global
CDR
plus
NACC
FTLD
score
of
3
and
who
were
rated
on
the
FAQ
had
FAQ
scores
of
25
or
more,
which
indicated
severe
functional
impairment.
...
Neuropsychiatric
symptoms
such
as
delusions,
hallucinations,
anxiety,
and
depression
are
considered
not
specific
to
FTD,
even
though
recent
studies
suggest
that
they
are
relatively
frequent
in
this
patient
population
[6][7][8],
have
different
trajectories
through
the
disease
course
[9],
and
cause
significant
suffering
and
poor
quality
of
life
for
both
the
patients
[10,11]
and
their
caregivers
[11].
Therefore,
the
early
detection
and
treatment
of
these
symptoms
might
have
relevant
implications
for
the
management
and
quality
of
life
of
FTD
patients
and
their
caregivers.
...
Background:
Neuropsychiatric
symptoms
cause
significant
suffering
and
poor
quality
of
life
for
patients
and
their
caregivers.
They
are
not
considered
specific
to
frontotemporal
dementia
(FTD);
therefore,
their
clinical
role
and
impact
might
be
underestimated.
Objective:
The
aims
of
the
present
study
are
to:
1)
describe
the
prevalence
of
neuropsychiatric
symptoms
in
FTD
starting
from
the
prodromal
stage,
2)
define
their
association
with
disease
severity,
3)
identify
symptoms
which
are
unrelated
to
FTD-
specific
symptoms,
and
4)
assess
their
association
with
clinical
features
and
outcomes.
Results:
In
this
retrospective
study,
we
analyzed
data
of
461
FTD
patients,
including
behavioral
variant
of
FTD
(bvFTD,
n
=
318)
and
primary
progressive
aphasia
(PPA,
n
=
143).
Neuropsychiatric
symptoms
were
assessed
using
the
Neuropsychiatric
Inventory,
and
patients’
staging
and
global
disease
severity
were
estimated
using
the
Clinical
Dementia
Rating
plus
NACC
FTLD.
Results:
The
most
common
neuropsychiatric
symptoms
in
prodromal
FTD
were
irritability
(48%),
depression
(35%),
and
anxiety
(34%);
delusions
were
reported
in
6%of
prodromal
bvFTD
cases.
The
severity
of
most
neuropsychiatric
symptoms
increased
with
global
disease
severity.
Psychosis
(delusions
and
hallucinations)
and
mood
symptoms
(depression
and
anxiety)
were
mostly
independent
from
FTD-
specific
symptoms.
Psychosis
was
associated
with
older
age,
higher
disease
severity,
shorter
survival
rate,
and
was
higher
in
bvFTD
than
in
PPA.
Conclusions:
Neuropsychiatric
symptoms
are
common
in
patients
with
FTD,
also
in
the
prodromal
phase.
Psychosis
might
be
unrelated
to
FTD
pathology,
and
be
associated
with
worse
clinical
outcomes.
The
prompt
detection
and
treatment
of
these
symptoms
might
improve
patient’s
management
and
quality
of
life.
It
is
well
established
that
cocaine
induces
an
increase
of
dendritic
spines
density
in
some
brain
regions.
However,
few
studies
have
addressed
the
role
of
this
neuroplastic
changes
in
cocaine
rewarding
effects
and
have
often
led
to
contradictory
results.
So,
we
hypothesized
that
using
a
rigorous
time-
and
subject-
matched
protocol
would
demonstrate...
Systematic
review:
The
authors
reviewed
the
literature
using
traditional
(eg,
PubMed)
sources
and
meeting
abstracts
and
presentations.
The
CDR
plus
NACC
FTLD
(previously
called
FTLD-
CDR)
was
developed
in
2008
to
improve
characterization
of
cognitive
and
global
function
in
FTLD,
although
there
had
been
no
global
rating
scale
for
it.
These
relevant
citations
are
appropriately
cited.
Also
reaching
the
NACC
Top
10
is
Frankie
And
The
Witch
Fingers.
Containing
neither
a
person
named
Frankie
nor
members
with
witch
fingers
(that
we
know
of
anyway),
the
band
began
in
Bloomington,
IN
as
a
solo
project
for
Dylan
Sizemore
in
2013.
Now
based
in
Los
Angeles,
Frankie
And
The
Witch
Fingers
is
a
quartet
and
have
released
seven
LPs,
including
their
latest,
Data
Doom
(RAS/Greenway), which climbs 14-9, giving them their first Top 10 on the NACC 200. Also reaching
the
Top
10
this
week is a band we featured a few weeks ago: Deeper. They rise 13-7 for their first NACC 200 Top
10
as
well. The fronto-striatal circuitry, involving the nucleus accumbens, ventral tegmental area, and
prefrontal cortex, mediates goal-directed behavior and is targeted by both drugs of abuse and HIV-1
infection. Acutely, both drugs and HIV-1 provoke increased dopamine activity within the circuit.
However,
chronic exposure to drugs or HIV-1 leads to dysregulation of the dopamine system as a result of
fronto-striatal adaptations to oppose the effects of repeated instances of transiently increased
dopamine. Specifically, chronic drug use leads to reduced dopaminergic tone, upregulation of
dopamine transporters, and altered circuit connectivity, sending users into an allosteric state in which
goal-directed behaviors are dysregulated (i.e., addiction). Similarly, chronic exposure to HIV-1, even
with
combination antiretroviral therapy (cART), dysregulates dopamine and dopamine transporter
function
and
alters connectivity of the fronto-striatal circuit, contributing to apathy and clinical symptoms of HIV-
1 associated neurocognitive disorders (HAND). Thus, in a drug user also exposed to HIV-1,
dysregulation of the fronto-striatal dopamine circuit advances at an exacerbated rate and appears to
be
driven by mechanisms unique from those seen with chronic drug use or HIV-1 exposure alone. We
posit that the effects of drug use and HIV-1 infection on microglia interact to drive the progression
of
motivational dysfunction at an accelerated rate. The current review will therefore explore how the
fronto-striatal circuit adapts to drug use (using cocaine as an example), HIV-1 infection, and both
together; emphasizing proper methods and providing future directions to develop treatments for
pathologies disrupting goal-directed behaviors and improve clinical outcomes for affected patients.
[Figure not available: see fulltext.]. © 2020, Springer Science+Business Media, LLC, part of Springer
Nature. Background: Chronic morphine treatments produce important morphological changes in
multiple brain areas including the nucleus accumbens. Methods: In this study, we have investigated
the
effect of chronic morphine treatment at a relatively low dose on the morphology of medium spiny
neurons in the core and shell of the nucleus accumbens in rats 1 day after the last injection of a
chronic morphine treatment (5 mg/kg once per day for 14 days). Medium spiny neurons were labeled
with
1,1' dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate crystal and analyzed by confocal
laser-scanning microscope. Results: Our results show an increase of thin spines and a decrease of
stubby spines specifically in the shell of morphine-treated rats compared with control. Since
morphine-treated rats also presented an elevation of corticosterone level in plasma, we explored
whether spine alterations induced by morphine treatment in the nucleus accumbens could be affected
by
the
depletion of the hormone. Thus, bilaterally adrenalectomized rats were treated with morphine in the
same conditions. No more alteration in stubby spines in the shell was detected in morphine-treated
rats with a depletion of corticosterone, while a significant increase was observed in mushroom
spines
in
the
shell and stubby spines in the core. Regarding the thin spines, the increase observed with morphine
compared with saline was lower in adrenalectomized rats than in nonadrenalectomized animals.
Conclusion: These results indicate that dendritic spine remodeling in nucleus accumbens following
chronic morphine treatment at relatively low doses is dependent on corticosterone levels. Maria C.
Tartaglia—nothing to disclose. Kelley Faber—receives research support from NIH. Abbreviations:
BEHAV, behavior/comportment/personality; bvFTD, behavioral variant frontotemporal dementia;
CDR-SB, sum of the boxes score of the six domains of the CDR; CDR plus NACC FTLD-SB, sum
of
the
boxes score of the six domains of the CDR plus the behavior/comportment and language domains;
FTLD,
frontotemporal
lobar degeneration; LANG, language; MCI, mild cognitive impairment; MCI-beh, mild behavioral
change; MCI-cog, mild cognitive impairment; nfvPPA, non-fluent/agrammatic variant primary
progressive
aphasia; svPPA, semantic variant primary progressive aphasia. As demonstrated with our analysis, the
CDR
was
not
sensitive in detecting early symptomatology of FTLD. The CDR was originally developed for
assessing global functions and cognition on AD dementia patients. While there were domains for
MEM impairment and disorientation typically seen in AD patients, there were no domains on
behavioral
disturbances or language impairment. Furthermore, the six domains of the CDR were not weighed
equally in determining the global CDR score; the MEM domain was designated as the primary
domain and the other five domains as secondary. If only one domain, other than the MEM domain, is
rated
>
0, global CDR is calculated to be 0. In developing the scoring rules for the global CDR plus NACC
FTLD
rating, eight domains, including the BEHAV and LANG domains, were weighted equally to
determine the global score, and the global CDR plus NACC FTLD score will become > 0 if any of
the
eight domains were rated as > 0. Diana Kerwin—has served on an Advisory Board for AbbVie and
as
site
PI for studies funded by Roche/Genentech, AbbVie, Avid, Novartis, Eisai, Eli Lilly, and UCSF. As
of
2015, India has over 4000 engineering colleges in various states which include IITs Institutions. Of
late the quality of engineering graduates passing out of private engineering institutions has degraded
to
the
extent that majority of them are unemployable. Due to outburst in quantity of engineering
institutions, the quality of institutions h... (a) Distribution of agitation with respect to dementia
severity; (b) distribution of agitation with respect to Z-drug use; (c) mean score over NACC visit,
stratified by age group; and (d) mean score over NACC visit, stratified by number of visits
completed. Cross-sectional analyses were performed on the baseline visit of the ARTFL/LEFFTDS
Consortium
study. Demographic, clinical, and genetic characteristics of the study participants were compared
among each clinical diagnostic group, and were analyzed by the Kruskal-Wallis test to assess
differences. The frequency of global CDR plus NACC FTLD or global CDR scores for MCI-beh,
MCI-
cog,
and
three subtypes of FTDs (bvFTD, svPPA, and nfvPPA) were calculated to evaluate how well the
CDR
plus
NACC
FTLD
and
CDR
detected the early clinical changes of the diagnoses. Weighted kappa statistics measured interrater
reliability of the two sites on the global CDR plus NACC FTLD score and the global CDR score,
and
the
intraclass correlation (ICC) measured interrater reliability on the CDR plus NACC FTLD-SB and
CDR-SB. Weighted Kappa statistics or ICC values of > 0.8 are considered having a very good
strength of agreement. Statistical analyses were performed using SAS (version 9.4; SAS Institute,
Inc., Cary, North Carolina). Anhedonia or inability to experience pleasure is the sign of various
neuropsychiatric
conditions. Current treatment options do not provide adequate control of anhedonia. The present
study
was
conducted to evaluate the protective effects of valproic acid (VPA) as a nonspecific histone
deacetylase (HDAC) inhibitor to reverse the effects of stress on induction of anhedonia and explore
possible mechanisms. To induce anhedonia, a rat model of chronic unpredictable mild stress (CUMS)
was
established. Animals were assigned into no stress, stress (6 weeks of CUMS) and two treatment
groups. VPA treatment was carried out for 4 continuous weeks (200 mg/kg/day). Behavioral
assessments were performed using sucrose consumption (SCT) and new object recognition (NOR)
tests. The expression of genes was evaluated using qRT-PCR. The cell density was determined using
Nissl staining. Rats with CUMS showed depressive-like behaviors and impaired memory
performance compared with the non-stressed group (p < 0.01). Moreover, they had significantly
higher levels of HDAC3 and MC4R expression in the nucleus accumbens (NAc) compared to the
non-stressed group (p < 0.01). The NAc cell density was significantly higher in the non-stressed rats
(p < 0.05). Corticosterone plasma level was increased in the CUMS compared to the non-stressed
group (p < 0.05). In the CUMS + VPA subgroup, the corticosterone (CORT) plasma level was lower
compared with the CUMS + Saline and/or the CUMS groups (p < 0.05). These findings suggest that
VPA can improve anhedonia and stress. Although the protective effect of VPA might link to
decreasing HDAC3 and MC4R genes expression in NAc. Table 3 demonstrates the interrater
reliability study regarding two sites and 40 study participants, and the ratings for each case for each
of the sites are shown in the supporting information. Most participants were middle aged, and all
were white with nearly equal sex ratio and at least 12 years of education. All participants with the
diagnoses of CN, MCI-beh, and MCI-cog were members of familial FTD with either MAPT,
c9orf72, or GRN mutations. Twenty participants (50%) were CN; nine participants (22.5%) were
either MCI-beh or MCI-cog; eleven participants (27.5%) were diagnosed as FTD, ALS, or AD.
Interrater reliability of global CDR plus NACC FTLD scores assessed by weighted kappa statistic
was very good (weighted κ = 0.84 [95% confidence interval (CI) 0.72–0.96]) and comparable to the
global CDR scores (weighted κ = 0.84 [95% CI 0.72–0.97]). Interrater reliability of the CDR plus
NACC FTLD-SB assessed by ICC was also very good (ICC = 0.95 [95% CI 0.87–0.98]) and
comparable to the CDR-SB (ICC = 0.95 [95% CI 0.86–0.98]). Overall ratings of NAC based on
clinical studies presented by condition. ... this within the CDR plus NACC FTLD alongside the new
neuropsychiatric module also leads to more participants being considered prodromal (6% of people
were asymptomatic on the CDR plus NACC FTLD but prodromal on the CDR plus NACC FTLD-
N-B+) (figure 5) as well as clinically judged symptomatic participants being considered as more
severe on the new scale, particularly those with a diagnosis of bvFTD (figure 4). Analysis of
individual genetic mutation groups shows most of this change is in C9orf72 mutation carriers (online
supplemental figure 3). ...
Mario
F.
Mendez—receives
research
support
from
NIH.
Location:
Google
Maps
Semantic
Scholar
is
a
free,
AI-
powered
research
tool
for
scientific
literature,
based
at
the
Allen
Institute
for
AI.
AMAL
College,
Kotturu
Junction,
...
The
specific
regions
in
the
genome
rich
in
histone
H3.3
are
believed
to
indicate
DNA
sequences
of
genes
binding
with
transcription
factors
involved
in
the
cocaine-
induced
plasticity
(e.g.,
Npas4,
Nptx2,
Pmepa1,
Vgf,
and
Fosb)
[24].
Alterations
to
the
expression
of
the
relevant
genes
may
induce
changes
in
BDNF
concentration
[25,26],
morphogenesis
of
dendrites
and
the
dendritic
spines,
along
with
an
increase
in
their
density
[27],
and
clustering
of
AMPARs
in
synapses
[21].
The
consequence
of
these
processes
could
be
behavioral
reactions,
such
as
cocaine-
conditioned
place
preference,
drug
self-
administration,
cocaineinduced
locomotor
activity,
and
spatial
memory
disturbances
[24].
...
The
participants
with
dementia/
motor
neuron
disease/
movement
disorder
due
to
bvFTD,
svPPA,
nfvPPA,
logopenic
variant
primary
progressive
aphasia
(lpvPPA),
FTD-
ALS,
ALS,
CBS,
PSP-
RS,
and
AD
were
diagnosed
and
classified
based
on
the
widely
accepted
published
criteria
for
each
disease.8-
13
Asymptomatic
or
mildly
symptomatic
participants
who
were
in
kindreds
with
known
FTLD-
related
gene
mutations
fell
into
three
groups.
Participants
who
did
not
have
any
detectable
cognitive
impairment,
behavioral
disturbances,
or
motor
impairment
were
categorized
as
“CN.”
“MCI-
cog” included all types of MCI (single domain amnestic MCI, multiple domain amnestic MCI, single
domain non-amnestic MCI, and multiple domain non-amnestic MCI), and was applied to
participants
who
showed objective cognitive decline not normal for age but not demented and were capable of
essentially normal functioning in activities.14-16 “MCI-beh” was applied to participants who
exhibited early mild changes in BEHAV (including: 1, behavioral disinhibition; 2, apathy/inertia; 3,
loss of sympathy/empathy; 4, perseverative/stereotyped/compulsive/ritualistic behavior; and 5,
hyperorality/dietary changes), but were not demented nor met criteria for probable bvFTD.8
Importantly, particularly in familial FTD, there are circumstances in which delusions, hallucinations,
and
other forms of odd behavior may be part of the evolving behavioral phenotype. Therefore, the
diagnosis of MCI-behavior is a loosely defined clinical diagnosis which will be operationalized with
more rigor in the future after more data are gathered and analyzed. Identified across multiple
psychiatric disorders, the dopamine (DA) transporter (DAT) Ala559Val substitution triggers non-
vesicular, anomalous DA efflux (ADE), perturbing DA neurotransmission and behavior. We have
shown that DAT Val559 mice display a waiting impulsivity and changes in cognitive performance
associated with enhanced reward motivation. Here, utilizing a within-subject, lever-pressing
paradigm designed to bias the formation of goal-directed or habitual behavior, we demonstrate that
DAT Val559 mice modulate their nose-poke behavior appropriately to match context, but
demonstrate a perseverative checking behavior. Although DAT Val559 mice display no issues with
the
cognitive
flexibility required to acquire and re-learn a visual pair-wise discrimination task, devaluation of
reward evoked habitual reward seeking in DAT Val559 mutants in operant tasks regardless of
reinforcement schedule. The direct DA agonist apomorphine also elicits locomotor stereotypies in
DAT Val559, but not WT mice. Our observation that dendritic spine density is increased in the dorsal
medial striatum (DMS) of DAT Val559 mice speaks to an imbalance in striatal circuitry that might
underlie the propensity of DAT Val559 mutants to exhibit compulsive behaviors when reward is
devalued. Thus, DAT Val559 mice represent a model for dissection of how altered DA signaling
perturbs circuits that normally balance habitual and goal-directed behaviors. High and low doses of
cocaine induce CPP and DeS increase in the NAcc core and shell of adolescent rats. CPP was
induced
in
adolescent rats with cocaine at 5 or 20 mg/kg. Immediately after the test, brains were processed for
DeS analysis according to materials and methods. CPP scores were expressed the means 6 S.E.M.
(A) (one-way ANOVA, F 2,17 = 4.8, p,0.05). Total DeS density was expressed as spines/mm (mean
6 S.E.M.) in MSN from the NAcc core (C) (one-way ANOVA, F 2,17 = 28.83, p,0.001) and shell (E)
(one-way ANOVA, F 2,17 = 12.25, p,0.001). Pearson correlation analysis between CPP score and
DeS density in both core (r = 0.54, p = 0.006, closed triangles) and shell (r = 0.42, p = 0.003, open
triangles) is shown in B. Density of mushroom, stubby, branched or thin spines was expressed as
spines/mm (mean 6 S.E.M.) in MSN from the NAcc core (D) (one-way ANOVA mushroom, F 2,17 =
1.88, p = 0.181; one-way ANOVA stubby, F 2,17 = 4.937, p,0.05; one-way ANOVA branched, F
2,17 = 0.7727, p = 0.477; one-way ANOVA thin, F 2,17 = 22.36, p,0.001) and shell (F) (one-way
ANOVA mushroom, F 2,17 = 1.143, p = 0.342; one-way ANOVA stubby, F 2,17 = 0.080, p = 0.461;
one-way ANOVA branched, F 2,17 = 3.326, p = 0.06; one-way ANOVA thin, F 2,17 = 12.22,
p,0.001). * p,0.05, ** p,0.01, *** p,0.001 vs saline group, Dunett's test, n = 6 to 8 animals/group.
doi:10.1371/journal.pone.0030241.g003 ... Эффективность N-ацетилцистеина изучали при
многих неврологических заболеваниях, включая нейродегенеративные заболевания,
хроническую и невропатическую боль [9,21]. Доклинические данные подтверждают
положительное влияние N-ацетилцистеина на когнитивные функции в моделях животных с
митохондриальной дисфункцией, наследственными нарушениями обмена веществ,
нейротоксичностью тяжелых металлов и болезнью Альцгеймера [22,23]. ... Average NAcc
responses for each subtype in anticipation period (a) and outcome period (b) with standard errors of
mean. The CDR® Dementia Staging Instrument, which we will refer to as the CDR hereafter, is a
global assessment scale originally developed in the early 1980s and designed to evaluate cognitive
/functional levels and severity of AD patients.1, 2 The CDR consists of six cognitive/functional
domains: MEM, ORI, judgment and problem solving, community affairs, home and hobbies, and
personal care (CARE). Based on the semi-structured interview from both a patient and a
knowledgeable informant (typically a close family member of a patient), each category domain is
rated on a five-point scale ranging from 0 (normal), 0.5 (questionably or minimally impaired), 1
(mildly but definitely impaired), 2 (moderately impaired), to 3 (severely impaired). The CARE
domain does not have a rating of 0.5, and so, is rated on a four-point scale. The sum total of the
ratings of the six domains is calculated to create the CDR sum of boxes (CDR-SB). The global CDR
score is derived from the six domains under the published scoring rules, and rated on a five-point
scale (0/0.5/1/2/3).2 In calculating the global CDR score by these scoring rules, MEM is considered
the
primary
domain and the five other domains as secondary so that global CDR score > 0 requires a score of 0.5
at
minimum for the MEM domain. In other words, it is possible to have the global CDR score of 0
despite mild impairment in one or more non-MEM domains, which is common in mild FTLD
spectrum disease patients. The CDR has served as one of the most widely used global clinical rating
scales in clinical research and clinical trials for AD. On the other hand, because the CDR was
originally created for evaluating AD patients, it weighs MEM impairment the highest and lacks
specific
domains assessing language or behavioral disturbance. Features Sort by Relevance Rodney
Pearlman—employed by the Bluefield Project. ... Nevertheless, the observed limited improvement in
our analysis suggested there are other probable mechanisms associated with cognitive impairment
which cannot improve by CPAP, like the degeneration and death of neurons and the dysfunction of
the
blood-brain barrier [49,50]. In addition, the shared genetic factors like allele e4 of APOE, elevated
inflammation proteins of C-reaction protein, and tumor necrosis factor-α between OSA and
cognitive
impairment
were
also worth to be studied in the future [51][52][53][54]. ... Show submenu for "Read" section
Association between changing hypnotic use status between previous and current visit on MMSE
scores (higher scores represent better cognitive function) at previous and current visit (a–c). Mean
scores stratified by current hypnotic use, with inverse probability weights used to account for
differences in prior predictors of hypnotic use (d–f). (a) Z-drug; (b) BZD; and (c) antipsychotics.
Data from the NACC data set. Association between changing hypnotic use status between previous
and
current visit on depression (measured by GDS, higher scores represent more depressive symptoms)
scores at previous and current visit (a–c). Mean scores stratified by current hypnotic use, with
inverse probability weights used to account for differences in prior predictors of hypnotic use (d–f).
(a) Z-drug; (b) BZD; and (c) antipsychotics. Data from the NACC data set. As of 2015, India has
over 4000 engineering colleges in various states which include IITs Institutions. Of late the quality of
engineering graduates passing out of private engineering institutions has degraded to the extent that
majority of them are unemployable. Due to outburst in quantity of engineering institutions, the
quality of institutions h... ... Table 1 illustrates their sociodemographic and clinical features. bvFTD
were more frequently males than nfvPPA (57% versus 34%, p< 0.001), and less educated than
nfvPPA and svPPA 22 (13) b [6] 25 (10) [3] 0.008 28 (3) [4] 28 ( , p< 0.001) than nfvPPA, and more
severe neuropsychiatric symptoms (17 ± 17) than nfvPPA (8 ± 12, p< 0.001) and svPPA (12 ± 12, p
< 0.001). Finally, in prodromal FTD, Goldman scores were not equally distributed across phenotypes
(p = 0.026), due to the higher frequencies of patients with Goldman score = 4 (than with Goldman
scores = 1-2) and of patients with bvFTD (than with PPA). ... Rosa Rademakers—receives research
funding from NIH and the Bluefield Project to Cure Frontotemporal Dementia. ... SPD can be
comorbid with other mental health disorders like anxiety or obsessive-compulsive disorder (OCD).
Interventions such as cognitivebehavioral therapy (CBT), involving habit reversal training and/or
stimulus control, are the first-line treatment followed by medications, such as selective serotonin
reuptake inhibitors (SSRI), which treat the underlying mental health issues [1,2]. N-acetyl cysteine
(NAC) is an amino acid derivative generally known for its use after an acetaminophen overdose and
as a mucolytic [2]. ... Though College secured NAAC Accredited B++ Grade, as a team we are
striving for A+. All our efforts for the past 1 years was aimed towards acheving a better goal and a
better life to students and society. Madeline Potter—receives research support from NIH. Read (a)
Distribution of animal fluency with respect to dementia severity; (b) distribution of animal fluency
with respect to Z-drug use; (c) mean score over NACC visit, stratified by age group; and (d) mean
score over NACC visit, stratified by number of visits completed. Austin, TX duo The Black Pumas
spends a second week #1 on the NACC Singles Chart this week with “More Than A Love Song.”
The song comes from their forthcoming second LP, Chronicles Of A Diamond, due October 27. The
song also spends a fourth week atop the R&B/Soul Chart. Only one single collects enough adds to
place inside the NACC 200 Top 30 Adds Chart this week. “Modern Girl” is (so far anyway) a stand-
alone single from super-producer and songwriter Jack Antonoff and his band Bleachers that was
featured in the final season of Netflix’s Sex Education.