Journal review

13/08/2019
Dr pratheesh
 Objective 
• Studies have independently shown associations of
lower hemoglobin levels with larger admission
intracerebral hemorrhage (ICH) volumes and worse
outcomes.
• This study investigated whether lower admission
hemoglobin levels are associated with more
hematoma expansion (HE) after ICH and whether this
mediates lower hemoglobin levels' association with
worse outcomes.
 Methods 
• Consecutive patients enrolled between 2009 and 2016
to a single-center prospective ICH cohort study with
admission hemoglobin and neuroimaging data to
calculate HE (>33% or >6 mL) were evaluated.
• The association of admission hemoglobin levels with
HE and poor clinical outcomes using modified Rankin
Scale (mRS 4–6) were assessed using separate
multivariable logistic regression models.
• Mediation analysis investigated causal associations
among hemoglobin, HE, and outcome.
 Results
•  256 patients with ICH meeting inclusion criteria, 63 (25%) had
HE. Lower hemoglobin levels were associated with increased
odds of HE (odds ratio [OR] 0.80 per 1.0 g/dL change of
hemoglobin; 95% confidence interval [CI] 0.67–0.97) after
adjusting for previously identified covariates of HE (admission
hematoma volume, antithrombotic medication use, symptom
onset to admission CT time) and hemoglobin (age, sex).
• Lower hemoglobin was also associated with worse 3-month
outcomes (OR 0.76 per 1.0 g/dL change of hemoglobin; 95%
CI 0.62–0.94) after adjusting for ICH score.
• Mediation analysis revealed that associations of lower
hemoglobin with poor outcomes were mediated by HE (p =
0.01).
 Conclusions 
• Further work is required to replicate the associations
of lower admission hemoglobin levels with increased
odds of HE mediating worse outcomes after ICH.
• If confirmed, an investigation into whether
hemoglobin levels can be a modifiable target of
treatment to improve ICH outcomes may be
warranted.
 Objective 
• To investigate the relationship between
cognitive reserve (CR) and clinical progression
across the Alzheimer disease (AD) spectrum.
 Methods 
• They selected 839 β-amyloid (Aβ)–positive participants with normal
cognition (NC, n = 175), mild cognitive impairment (MCI, n = 437),
or AD dementia (n = 227) from the Alzheimer's Disease
Neuroimaging Initiative (ADNI). CR was quantified using
standardized residuals (W scores) from a (covariate-adjusted) linear
regression with global cognition (13-item Alzheimer's Disease
Assessment Scale–cognitive subscale) as an independent variable
of interest, and either gray matter volumes or white matter
hyperintensity volume as dependent variables.
• These W scores, reflecting whether an individual's degree of
cerebral damage is lower or higher than clinically expected, were
tested as predictors of diagnostic conversion (i.e., NC to MCI/AD
dementia, or MCI to AD dementia) and longitudinal changes in
memory (ADNI-MEM) and executive functions (ADNI-EF).
 Results 
• The median follow-up period was 24 months (interquartile range
6–42). Corrected for age, sex, APOE4 status, and baseline cerebral
damage, higher gray matter volume-based W scores (i.e., greater
CR) were associated with a lower diagnostic conversion risk
(hazard ratio [HR] 0.22, p < 0.001) and slower decline in memory
(β = 0.48, p < 0.001) and executive function (β = 0.67, p < 0.001).
• Stratified by disease stage, they found similar results for NC
(diagnostic conversion: HR 0.30, p = 0.038; ADNI-MEM: β =
0.52, p = 0.028; ADNI-EF: β = 0.42, p = 0.077) and MCI (diagnostic
conversion: HR 0.21, p < 0.001; ADNI-MEM: β = 0.43, p= 0.003;
ADNI-EF: β = 0.59, p < 0.001), but opposite findings (i.e., more
rapid decline) for AD dementia (ADNI-MEM: β = −0.91, p = 0.002;
ADNI-EF: β = −0.77, p = 0.081).
 Conclusions
•  Among Aβ-positive individuals, greater CR
related to attenuated clinical progression in
predementia stages of AD, but accelerated
cognitive decline after the onset of dementia.
 Objective 

• To investigate the temporal relationship

among pre diagnostic body mass index (BMI),
weight change, and risk of amyotrophic lateral
sclerosis (ALS).
 Methods
•  From the compulsory Norwegian tuberculosis screening
program, they collected objectively measured BMI from
85% of all citizens (near 1.5 million) between 20 and 70
years of age living in 18 of 19 Norwegian counties between
1963 and 1975.
• For those who participated in later health surveys, they
collected further information on weight change, lifestyle,
and health.
• They identified ALS cases until September 2017 through
national registries of diagnoses at death and at encounters
with the specialist health service. Both Cox hazard models
and flexible parametric survival models were fitted to
address our research question.
 Results 
• They identified 2,968 ALS cases during a mean of 33
(maximum 54) years follow-up. High prediagnostic BMI was
associated with low subsequent ALS risk across the typical
ALS ages in both sexes. Overall, hazard ratio (HR) for ALS per
5-unit increase in prediagnostic BMI was 0.83 (95%
confidence interval [CI] 0.79–0.88).

• After an initial increase during the first 10 years, it decreased

almost linearly throughout the observation period and was
0.69 (95% CI 0.62–0.77) after 50 years. Those in the quartile
with highest weight gain had lower ALS risk than those in the
lowest quartile (HR 0.63, 95% CI 0.44–0.89).
 Conclusion
•  High BMI and weight gain are associated with
low ALS risk several decades later. The
strength of the association between BMI and
ALS risk increases up to 50 years after BMI
measurement.
 Objective 
• To prospectively examine the association
between low-density lipoprotein (LDL)
cholesterol (LDL-C) concentrations and
intracerebral hemorrhage (ICH) risk.
 Methods 
• The current cohort study included 96,043
participants (mean age 51.3 years) who were free of
stroke, myocardial infarction, and cancer at baseline
(2006). Serum LDL-C concentrations were assessed in
2006, 2008, 2010, and 2012.
• Cumulative average LDL-C concentrations were
calculated from all available LDL-C data during that
period. Incident ICH was confirmed by review of
medical records.
 Results 
• They identified 753 incident ICH cases during 9 years of
follow-up. The ICH risk was similar among participants
with LDL concentrations of 70 to 99 mg/dL and those with
LDL-C concentrations ≥100 mg/dL.
• In contrast, participants with LDL-C concentrations <70
mg/dL had a significantly higher risk of developing ICH
than those with LDL-C concentrations of 70 to 99 mg/dL;
adjusted hazard ratios were 1.65 (95% confidence interval
[CI] 1.32–2.05) for LDL-C concentrations of 50 to 69 mg/dL
and 2.69 (95% CI 2.03–3.57) for LDL-C concentrations <50
mg/dL.
 Conclusions 
• They observed a significant association between
lower LDL-C and higher risk of ICH when LDL-C was
<70 mg/dL, and the association became
nonsignificant when LDL-C ≥70 mg/dL.
• These data can help determination of the ideal LDL
range in patients who are at increased risk of both
atherosclerotic disease and hemorrhagic stroke and
guide planning of future lipid-lowering studies.
 Objective
• they evaluated the efficacy of muscle-targeted
nutritional support on the functional
outcomes of multidisciplinary intensive
rehabilitation treatment (MIRT) in patients
with Parkinson disease (PD) or parkinsonism.
 Methods 
• They conducted a pragmatic, bicentric, randomized (1:1),
assessor-blind controlled trial (Protein, Leucine and Vitamin D
Enhancing Rehabilitation [PRO-LEADER]; April 2017 to January
2018) in cognitively intact patients with PD or parkinsonism and
undergoing a 30-day MIRT. Patients (n = 150) received a standard
hospital diet with or without a whey protein–based nutritional
supplement enriched with leucine and vitamin D twice daily.
• The primary efficacy endpoint was the increase in the distance
walked during a 6-minute walking test (6MWT). Secondary
endpoints were changes in 4-meter walking speed, Timed Up and
Go test (TUG), Berg balance scale, handgrip strength, Self-
assessment Parkinson's Disease Disability Scale, body weight, and
skeletal muscle mass (SMM).
 Results 
• Nutritional support resulted in greater increase in the
distance walked during 6MWT (mean 69.6 meters [95%
confidence interval (CI) 60.7–78.6]) than no support
(51.8 meters [95% CI 37.0–66.7]): center-adjusted mean
difference, 18.1 meters (95% CI 0.9–35.3) (p = 0.039).
• Further adjustment for changes in dopaminergic therapy
and SMM yielded consistent results: mean difference,
18.0 meters (95% CI 0.7–35.2) (p= 0.043). A meaningful
effect was also found for the following secondary
endpoints: 4-meter walking speed (p= 0.032), TUG (p =
0.046), SMM, and SMM index (p = 0.029).
 Conclusion
•  The consumption of a whey protein–based
nutritional formula enriched with leucine and
vitamin D with MIRT improved lower
extremity function and preserved muscle mass
in patients with PD or parkinsonism.
thank you