Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Dec. 17, 2024
Throughout
adulthood
and
ageing
our
brains
undergo
structural
loss
in
an
average
pattern
resembling
faster
atrophy
Alzheimer's
disease
(AD).
Using
a
longitudinal
adult
lifespan
sample
(aged
30-89;
2–7
timepoints)
four
polygenic
scores
for
AD,
we
show
that
change
AD-sensitive
brain
features
correlates
with
genetic
AD-risk
memory
decline
healthy
adults.
We
first
risk
links
more
than
expected
age
early
Braak
regions,
find
this
extends
beyond
APOE
genotype.
Next,
run
machine
learning
on
AD-control
data
from
the
Disease
Neuroimaging
Initiative
using
trajectories
conditioned
age,
to
identify
model
their
Genetic
linked
multivariate
across
many
features,
most
individuals
over
~50
are
accelerated
trajectory
of
regions.
Finally,
high
adults
elevated
showed
through
adulthood,
compared
less
change.
Our
findings
suggest
quantitative
AD
factors
detectable
individuals,
via
shared
ageing-
AD-related
neurodegeneration
occurs
along
continuum
tracks
adulthood.
This
study
shows
among
tracked
lives,
rates
correlate
decline,
degeneration
Alzheimer's-vulnerable
regions
is
continuous
phenomenon.
Brain and Neuroscience Advances,
Journal Year:
2025,
Volume and Issue:
9
Published: Jan. 1, 2025
Apolipoprotein
E
ε4
is
a
major
genetic
risk
factor
for
Alzheimer’s
disease,
and
some
apolipoprotein
carriers
show
disease–related
neuropathology
many
years
before
cognitive
changes
are
apparent.
Therefore,
studying
healthy
genotyped
individuals
offers
an
opportunity
to
investigate
the
earliest
in
brain
measures
that
may
signal
presence
of
disease-related
processes.
For
example,
subtle
functional
magnetic
resonance
imaging
connectivity,
particularly
within
default
mode
network,
have
been
described
when
comparing
ε3
carriers.
Similarly,
very
mild
impairments
episodic
memory
also
documented
Here,
we
use
naturalistic
activity
(movie
watching),
marker
encoding
(transient
connectivity
around
so-called
‘event
boundaries’),
potential
phenotype
differences
associated
with
genotype
large
sample
adults.
Using
Bayes
analyses,
found
strong
evidence
against
existence
allelic
status.
did
not
find
E-associated
ran
exploratory
analyses
examining:
system
segregation
across
whole
brain,
network.
We
conclude
has
little
or
no
effect
on
how
ongoing
experiences
processed
The
observed
studies
reflect
early
effects
pathology
Current Opinion in Neurology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 7, 2025
Purpose
of
review
This
focuses
on
the
role
psychological
factors
in
cognitive
aging
and
dementia,
an
area
that
has
received
less
attention
compared
to
other
modifiable
(e.g.
sleep,
physical
activity,
so
on)
or
reduction
disease
risk.
Recent
findings
A
range
mental
health
aspects,
including
clinical
symptoms,
stable
personality
traits,
more
specific
constructs
processes
repetitive
negative
thinking,
purpose
life),
are
associated
with
dementia
Psychological
can
either
serve
as
protective
risk
elements,
influencing
brain
through
general
mechanisms,
stress
regulation
impact
several
biological
systems,
well
modulate
resistance
resilience
Alzheimer's
age-related
changes.
Protective
traits
linked
healthier
lifestyle
habits,
while
behaviors,
may
function
across
lifespan,
suggesting
benefits
for
education
from
early
life.
Summary
The
emphasizes
need
greater
focus
optimizing
being,
particularly
at-risk
populations,
suggests
interventions
should
be
tailored
individuals’
values
life
purposes.
Additionally,
further
research
is
needed
explore
neurobiological
mechanisms
which
psychologically
focused
influence
decline
dementia.
Neurology,
Journal Year:
2025,
Volume and Issue:
104(9)
Published: April 9, 2025
Female
sex
and
a
parental
history
of
Alzheimer
disease
(AD),
especially
maternal,
confer
increased
risk
AD.
Associations
between
sex,
or
affected
AD
parent's
biomarkers
are
less
clear.
We
examined
whether
influences
(1)
β-amyloid
(Aβ)
tau
burden/accumulation,
(2)
the
association
Aβ
burden,
(3)
brain
cognitive
resilience
to
burden.
The
sample
included
243
participants
from
Presymptomatic
Evaluation
Experimental
Novel
Treatments
for
cohort
in
Canada.
All
with
[18F]-NAV4694
[18F]-AV1451
PET
MRI
were
included.
differences
on
regional
burden/accumulation;
2-way
interactions
burden;
3-way
time,
deposition
hippocampal
volume
(brain
resilience)
cognition
(cognitive
over
time.
Participants
(69.4%
female)
aged
68.3
±
5.1
years
at
their
first
scans.
cognitively
unimpaired
baseline.
Longitudinal
data
available
242
(follow-up,
6.72
2.38
years),
including
238
(6.53
2.48
follow-up)
follow-ups
115
(4.4
0.6
follow-ups,
71
developed
mild
impairment.
Women
showed
greater
(standardized
β
=
0.13
0.3)
stronger
global
than
men
0.79
0.1).
Individuals
an
father
those
mother
0.65
Aβ-associated
atrophy
time
0.24
and,
surprisingly,
individuals
paternal
seemed
more
vulnerable
Aβ-related
spread
tau,
whereas
women
Aβ.
Understanding
sex-specific
could
allow
clinical
trial
precision
personalization.
A
major
limitation
reduced
analyses.
Human
fetal
development
has
been
associated
with
brain
health
at
later
stages.
It
is
unknown
whether
growth
in
utero,
as
indexed
by
birth
weight
(BW),
relates
consistently
to
lifespan
characteristics
and
changes,
what
extent
these
influences
are
of
a
genetic
or
environmental
nature.
Here
we
show
remarkably
stable
lifelong
positive
associations
between
BW
cortical
surface
area
volume
across
within
developmental,
aging
longitudinal
samples
(N
=
5794,
4–82
y
age,
w/386
monozygotic
twins,
followed
for
up
8.3
w/12,088
MRIs).
In
contrast,
no
consistent
effect
on
changes
was
observed.
Partly
effects
were
indicated
analysis
twin
discordance.
conclusion,
the
influence
prenatal
topography
reliable
through
lifespan.
This
early-life
factor
appears
association
reserve,
rather
than
maintenance.
Thus,
appear
omnipresent
spacetime
human
throughout
Optimizing
may
increase
reserve
life,
also
aging.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 3, 2024
Abstract
In
neuroimaging
research,
tracking
individuals
over
time
is
key
to
understanding
the
interplay
between
brain
changes
and
genetic,
environmental,
or
cognitive
factors
across
lifespan.
Yet,
extent
which
we
can
estimate
individual
trajectories
of
change
with
precision
remains
uncertain.
this
study,
estimated
reliability
structural
in
cognitively
healthy
adults
from
multiple
samples
assessed
influence
follow-up
number
observations.
Estimates
cross-sectional
measurement
error
variance
were
obtained
using
longitudinal
FreeSurfer
processing
stream.
Our
findings
showed,
on
average,
modest
two
years
follow-up.
Increasing
was
associated
a
substantial
increase
while
impact
increasing
observations
comparatively
minor.
On
2-year
studies
require
≈2.7
≈4.0
times
more
than
designs
follow-ups
4
6
achieve
comparable
statistical
power.
Subcortical
volume
exhibited
higher
compared
cortical
area,
thickness,
volume.
The
estimates
those
empirical
data.
affected
by
both
cohort’s
age
where
younger
had
lower
change,
preprocessing
pipeline
FreeSurfer’s
stream
notably
superior
cross-sectional.
Suboptimal
inflated
sample
size
requirements
compromised
ability
distinguish
aging.
This
study
underscores
importance
long-term
need
consider
research.
Human
fetal
development
has
been
associated
with
brain
health
at
later
stages.
It
is
unknown
whether
growth
in
utero,
as
indexed
by
birth
weight
(BW),
relates
consistently
to
lifespan
characteristics
and
changes,
what
extent
these
influences
are
of
a
genetic
or
environmental
nature.
Here
we
show
remarkably
stable
life-long
positive
associations
between
BW
cortical
surface
area
volume
across
within
developmental,
aging
longitudinal
samples
(N
=
5794,
4-82
years
age,
w/
386
monozygotic
twins,
followed
for
up
8.3
w/12,088
MRIs).
In
contrast,
no
consistent
effect
on
changes
was
observed.
Partly
effects
were
indicated
analysis
twin
discordance.
conclusion,
the
influence
prenatal
topography
reliable
through
lifespan.
This
early
life
factor
appears
association
reserve,
rather
than
maintenance.
Thus,
appear
omnipresent
spacetime
human
throughout
Optimizing
may
increase
reserve
life,
also
aging.
Brain,
Journal Year:
2024,
Volume and Issue:
148(1), P. 133 - 142
Published: June 18, 2024
Obese
adults
are
often
reported
to
have
smaller
brain
volumes
than
their
non-obese
peers.
Whether
this
represents
evidence
of
accelerations
in
obesity-driven
atrophy
or
is
instead
a
legacy
developmental
differences
established
earlier
the
lifespan
remains
unclear.
This
study
investigated
whether
early-life
adiposity
explain
numerous
adult
traits
commonly
attributed
mid-life
obesity.
We
used
two-sample
life
course
Mendelian
randomization
37
501
recruited
UK
Biobank
(UKB)
imaging
centres
from
2014,
with
secondary
analyses
6996
children
assessed
Adolescent
Brain
Cognitive
Development
Study
(ABCD)
2018.
Exposures
were
genetic
variants
for
childhood
(266
variants)
and
(470
derived
genome-wide
association
(GWAS)
407
741
UKB
participants.
Primary
outcomes
were:
total
volume;
grey
matter
volume,
thickness
surface
area;
white
volume
hyperintensities;
hippocampus,
amygdala
thalamus
at
mean
age
55
UKB.
Secondary
equivalent
measures
collected
10
ABCD.
In
UKB,
individuals
who
genetically
predicted
had
higher
levels
found
multiple
relative
intracranial
[e.g.
z-score
difference
normalized
per
category
increase
adiposity-95%
confidence
interval
(CI)
=
-0.20
(-0.28,
-0.12);
P
4
×
10-6].
These
effect
sizes
remained
essentially
unchanged
after
accounting
birthweight
current
obesity
multivariable
models,
whereas
most
observed
effects
attenuated
towards
null
(95%
CI)
0.06
(-0.05,
0.17);
0.3].
Observational
ABCD
showed
similar
pattern
changes
already
present
those
high
body
mass
index
by
[z-score
-0.10
(-0.13,
-0.07);
8
10-13],
follow-up
risk
score
providing
some
causal
early
age.
Sensitivity
revealed
that
many
these
likely
due
persistence
larger
head
gained
excess
weight
[childhood
0.14
(0.05,
0.23);
0.002],
rather
se.
Our
data
suggest
across
may
underlie
neuroimaging
obesity-related
later
life.
