Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: May 24, 2024
Alois
Alzheimer
described
the
first
patient
with
Alzheimer’s
disease
(AD)
in
1907
and
today
AD
is
most
frequently
diagnosed
of
dementias.
a
multi-factorial
neurodegenerative
disorder
familial,
life
style
comorbidity
influences
impacting
global
population
more
than
47
million
projected
escalation
by
2050
to
exceed
130
million.
In
USA
demographic
encompasses
approximately
six
individuals,
expected
increase
surpass
13
2050,
antecedent
phase
AD,
recognized
as
mild
cognitive
impairment
(MCI),
involves
nearly
12
individuals.
The
economic
outlay
for
management
AD-related
decline
estimated
at
355
billion
USD.
addition,
intensifying
prevalence
cases
countries
modest
intermediate
income
further
enhances
urgency
therapeutically
cost-effective
treatments
improving
quality
patients
their
families.
This
narrative
review
evaluates
pathophysiological
basis
an
initial
focus
on
therapeutic
efficacy
limitations
existing
drugs
that
provide
symptomatic
relief:
acetylcholinesterase
inhibitors
(AChEI)
donepezil,
galantamine,
rivastigmine,
N-methyl-D-aspartate
receptor
(NMDA)
allosteric
modulator,
memantine.
hypothesis
amyloid-β
(Aβ)
tau
are
appropriate
targets
have
potential
halt
progress
critically
analyzed
particular
clinical
trial
data
anti-Aβ
monoclonal
antibodies
(MABs),
namely,
aducanumab,
lecanemab
donanemab.
challenges
dogma
targeting
Aβ
will
benefit
majority
subjects
MABs
unlikely
be
“magic
bullet”.
A
comparison
benefits
disadvantages
different
classes
forms
determining
new
directions
research
alternative
drug
undergoing
pre-clinical
assessments.
we
discuss
stress
importance
treatment
co-morbidities,
including
hypertension,
diabetes,
obesity
depression
known
risk
developing
AD.
Journal of Translational Medicine,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: Jan. 27, 2025
Alzheimer's
disease
(AD)
is
the
most
frequent
neurodegenerative
disorder
worldwide.
The
great
variability
in
evolution
and
incomplete
understanding
of
molecular
mechanisms
underlying
AD
make
it
difficult
to
predict
when
a
patient
will
convert
from
prodromal
stage
dementia.
We
hypothesize
that
metabolic
alterations
present
at
level
brain
could
be
reflected
systemic
blood
serum
patients,
these
used
as
prognostic
biomarkers.
This
pilot
study
proposes
investigation
via
nuclear
magnetic
resonance
(NMR)
spectroscopy
consecutive
series
patients
including
57
affected
by
dementia
(AD-dem)
45
with
mild
cognitive
impairment
(MCI)
due
(MCI-AD).
As
control
group,
we
considered
31
subjects
whom
other
disorders
were
excluded
(MCI).
A
panel
26
metabolites
112
lipoprotein-related
parameters
was
quantified
logistic
LASSO
regression
algorithm
employed
identify
optimal
combination
metabolites-lipoproteins
their
ratios
discriminate
groups
interest.
In
training
set,
our
model
classified
AD-dem
MCI
an
accuracy
81.7%.
These
results
reproduced
validation
set
(accuracy
75.0%).
Evolution
MCI-AD
evaluated
over
time.
Patients
who
displayed
decrease
MMSE
<
1.5
point
per
year
lower
progression
rate:
obtained
division
18
rate
(MCI-AD
LR)
27
higher
HR).
calculated
using
4
features
identified
LR
HR
73.3%.
identification
potential
novel
peripheral
biomarkers
disease,
proposed
this
study,
opens
new
prospect
for
innovative
minimally
invasive
method
its
very
early
stages.
approach
able
sub-stratify
identifying
those
associated
faster
clinical
progression.
Alzheimer s Research & Therapy,
Journal Year:
2024,
Volume and Issue:
16(1)
Published: Aug. 1, 2024
Abstract
Several
(inter)national
longitudinal
dementia
observational
datasets
encompassing
demographic
information,
neuroimaging,
biomarkers,
neuropsychological
evaluations,
and
muti-omics
data,
have
ushered
in
a
new
era
of
potential
for
integrating
machine
learning
(ML)
into
research
clinical
practice.
ML,
with
its
proficiency
handling
multi-modal
high-dimensional
has
emerged
as
an
innovative
technique
to
facilitate
early
diagnosis,
differential
predict
onset
progression
mild
cognitive
impairment
dementia.
In
this
review,
we
evaluate
current
applications
including
history
research,
how
it
compares
traditional
statistics,
the
types
uses
general
workflow.
Moreover,
identify
technical
barriers
challenges
ML
implementations
Overall,
review
provides
comprehensive
understanding
non-technical
explanations
broader
accessibility
biomedical
scientists
clinicians.
Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 13, 2025
AbstractBackground:
Biological
age
can
be
quantified
by
composite
proteomic
scores,
called
aging
clocks.
We
investigated
whether
biological
acceleration
(a
discrepancy
between
chronological
and
age)
in
midlife
late-life
is
associated
with
cognitive
function
risk
of
dementia.
Methods:
used
two
population-based
cohort
studies:
Atherosclerosis
Risk
Communities
(ARIC)
Study
Multi-Ethnic
(MESA).
Proteomics-based
clocks
(PACs)
were
created
ARIC
at
(mean
age:
58
years,
n=11,758)
77
n=4,934)
using
elastic
net
regression
models
two-thirds
dementia-free
participants
validated
the
remaining
one-third
participants.
Age
(AA)
was
calculated
as
residuals
after
regressing
PACs
on
age.
PAC
MESA
62
n=5,829).
multivariable
linear
Cox
proportional
hazards
to
assess
association
AA
dementia
incidence,
respectively.
Results:
In
ARIC,
every
five
years
lower
global
function:
difference:
-0.11,
95%
confidence
interval
(CI):
-0.16,
-0.06)
-0.17,
CI:
-0.23,
-0.12
AA.
Consistently,
higher
(hazard
ratio
[HR]:
1.20
[CI:
1.04,
1.36])
more
prominently
when
(HR:
2.14
[CI:1.67,
2.73]).
Similar
findings
observed
study:
(difference:
-0.08
-0.14,
-0.03])
(HR:1.23
1.46]).
Conclusion:
Accelerated
–
defined
plasma
proteome
predicts
a
late-life.
Frontiers in Aging Neuroscience,
Journal Year:
2025,
Volume and Issue:
17
Published: March 20, 2025
Introduction
With
global
aging,
dementia
prevalence
rises.
While
long-chain
saturated
fatty
acids
show
anti-cognitive
decline
potential,
serum
tricosanoic
acid
(C23:0)’s
role
in
brain
regions
and
cognition
remains
unclear.
Methods
To
confirm
the
association
between
C23:0
population,
we
analyzed
gene
expression
data
from
Alzheimer’s
disease
(AD)
chip
set
(GSE118553)
available
Gene
Expression
Omnibus
(GEO)
database.
Additionally,
examined
1,127
adults
aged
60
years
older
who
participated
National
Health
Nutrition
Examination
Survey
(NHANES)
2011
2014.
explore
potential
metabolic
pathways
mechanisms
linking
to
cognitive
computational
platform
METAFlux
was
employed.
Results
Differential
analysis
identified
335
downregulated
477
upregulated
genes
AD
frontal
cortex.
Metabolite
showed
20
37
nutrients
(including
C23:0)
vs.
controls.
Population-level
(NHANES,
n
=
1,127)
confirmed
higher
associated
with
better
function.
Discussion
This
study
provides
strong
evidence
for
cortex-specific
reduced
highlights
its
as
a
marker.
Brain and Behavior,
Journal Year:
2025,
Volume and Issue:
15(3)
Published: March 1, 2025
A
variety
of
observational
studies
suggest
a
possible
connection
between
C-X-C
Motif
Chemokine
Ligand
5
(CXCL5)
and
vascular
dementia
(VaD),
though
the
exact
causal
relationship
is
still
uncertain.
This
research
aims
to
investigate
CXCL5
VaD
risk
through
Mendelian
randomization
(MR)
method
examine
phosphate-to-glucose
ratio
as
mediator.
Using
summary-level
data
from
genome-wide
association
(GWAS),
we
conducted
two-sample
MR
analysis
genetic
prediction
VaD.
Horizontal
pleiotropy,
heterogeneity,
sensitivity
analyses
were
also
performed
on
findings.
Additionally,
two-step
was
utilized
quantify
proportion
effect
mediated
by
ratio.
identified
that
higher
levels
(IVW:
p
=
0.022,
OR
1.265,
95%
CI
1.034-1.547)
increase
Tests
for
horizontal
pleiotropy
(p
>
0.05),
heterogeneity
supported
these
There
insufficient
robust
evidence
predispositions
have
any
significant
impact
0.254).
The
accounted
11.1%
in
associated
with
(95%
-12.3%
34.5%).
To
conclude,
our
confirms
link
shows
plays
mediating
role
segment
However,
most
effects
are
not
well
understood.
Additional
necessary
explore
other
potential
mediators
factors.
In
clinical
settings,
individuals
abnormally
elevated
may
need
be
monitored
an
increased
developing
BMC Public Health,
Journal Year:
2024,
Volume and Issue:
24(1)
Published: April 16, 2024
Abstract
Background
Age-related
cognitive
decline
has
a
significant
impact
on
the
health
and
longevity
of
older
adults.
Circulating
very
long-chain
saturated
fatty
acids
(VLSFAs)
may
actively
contribute
to
improvement
function.
The
objective
this
study
was
investigate
associations
between
arachidic
acid
(20:0),
docosanoic
(22:0),
tricosanoic
(23:0),
lignoceric
(24:0)
with
function
in
Methods
This
used
dataset
derived
from
2011–2014
National
Health
Nutrition
Examination
Survey
(NHANES).
A
total
806
adults
(≥
60
years)
were
included
who
underwent
comprehensive
testing
plasma
measurements.
Multivariable
linear
regression,
restricted
cubic
spline
(RCS),
interaction
analyses
assess
VLSFAs
Partial
Spearman’
s
correlation
analysis
examine
correlations
palmitic
(16:0),
high-density
lipoprotein
cholesterol,
low-density
triglycerides,
systemic
inflammatory
markers,
dietary
nutrients.
Results
regression
analysis,
adjusting
for
sociodemographic,
clinical
conditions,
lifestyle
factors,
showed
that
22:0
24:0
levels
positively
associated
better
global
(β
=
0.37,
95%
confidence
interval
[CI]
0.01,
0.73;
β
0.73,
CI
0.29,
1.2,
respectively)
as
well
CEARD-DR
Z-score
0.82,
0.36,
1.3
0.63,
1.8,
respectively).
RCS
higher
performance
both
CERAD-DR
tests.
Conclusions
suggests
are
be
important
biomarkers
recognizing
impairment,
supplementation
specific
(22:0
24:0)
an
intervention
improve
Further
studies
needed
elucidate
underlying
biological
mechanisms
