October Newsletter
In This Issue
Flu Shot Fizzle
But Is It Just Baby Fat?
Genetics + Inflammation = Dementia
A Better Model of Medical Care
Old-fashioned medicine with 21st Century convenience and technology
Quick Links
Join Our List
View my profile on LinkedIn 
Follow me on Twitter
I hope this newsletter finds you and your family well. I'm still trying to get caught up after all the October baseball excitement. This 2018 Brewers team really took us all on a great ride. It's great to see several players and our manager being recognized for well-deserved individual awards. Congratulations to them and to the entire organization on an excellent team effort. There are a lot of people who do a lot of work behind the scenes to bring us a great group of players on the field and allow us to enjoy a world-class stadium. All I'm hearing is that people can't wait until next year - I know from experience that February will be here before we know it!

It's flu shot time. We've seen signs at every pharmacy starting in August. Pundits are on the news telling us to get our flu shots as soon as possible. But when is the best time to get a flu shot? Should we get a flu shot in August or September or even October? The first article will give some guidance to this question.

Obesity is an increasing problem worldwide. We and our children are more obese than ever. When does our risk of obesity start? Is it in adulthood? The second article followed children from birth to age 18. The point in life that they found increased risk of adolescent obesity will shock you. 

Dementia has multiple likely causes. Alzheimer's dementia is one subset of dementia but has been shown to be strongly correlated with a genetic apolipoprotein marker produced in the liver and the brain. People who have this marker have a much higher chance of developing Alzheimer's dementia. This study found that people who have this marker can reduce their risk to the same as people without the marker by making some changes in their lifestyle. These changes will also reduce your risk of cardiovascular disease as well!

Click on the links the the left to check out our  web site .
Flu Shot Fizzle
Effectiveness of influenza vaccine wanes during flu season
Influenza viruses rapidly mutate which is why a different vaccine needs to be formulated every year. Current guidance from the CDC is to vaccinate as soon as the vaccine is available and continue as long as influenza is in circulation in the community. This has led to vaccines often being given in August and September, especially to those at highest risk (elderly nursing home residents). But is this the best thing to do? This study, from Clinical Infectious Diseases found a waning effectiveness of the vaccine over the flu season. The vaccine appears to lose around 16% effectiveness every 28 days after vaccination. Influenza typically peaks between December and March in the United States with most cases in January and February. Therefore, an individual vaccinated in early September could lose over half the effectiveness of the vaccine by the time flu season actually arrives in December and even more later during the peak of the flu season. 
  • Background:  In the United States it is recommended that health care providers offer influenza vaccination by October, if possible. However, if the vaccine's effectiveness soon begins to wane, the optimal time for vaccination may be somewhat later. We examined whether the effectiveness of influenza vaccine wanes during the influenza season with increasing time since vaccination.
  • Methods: We identified persons who were vaccinated with inactivated influenza vaccine from September 1, 2010 to March 31, 2017 and who were subsequently tested for influenza and respiratory syncytial virus (RSV) by a polymerase chain reaction test. Test-confirmed influenza was the primary outcome and days-since-vaccination was the predictor of interest in conditional logistic regression. Models were adjusted for age and conditioned on calendar day and geographic area. RSV was used as a negative control outcome.
  • Results: Compared with persons vaccinated 14 to 41 days prior to being tested, persons vaccinated 42 to 69 days prior to being tested had 1.32 (95% Confidence Interval (CI): 1.11 to 1.55) times the odds of testing positive for any influenza. The odds ratio (OR) increased in linear fashion by approximately 16% for each additional 28 days since vaccination; the OR was 2.06 (95% CI: 1.69 to 2.51) for persons vaccinated 154 or more days prior to being tested. No evidence of waning was found for RSV.
  • Conclusions: Our results suggest that effectiveness of inactivated influenza vaccine wanes during the course of a single season. These results may lead to reconsideration of the optimal timing of seasonal influenza vaccination.

Many people are concerned about the effectiveness of the influenza vaccine. We often see reports of the effectiveness (or lack of) of the influenza vaccine for a given year. A good year will see a vaccine reaching around 50% effectiveness overall (it will be more effective against some strains and less against others). Last year's vaccine was overall 36% effective. The vaccine was only 25% effective against the H3N2 strain (seen commonly last year) but against the H1N1  variant it was was 67% effective. It was around 42% effective against two influenza B strains. The numbers were better for children than adults though. Since we have a vaccine that is often less than 50% effective, the idea of losing 16% effectiveness of the vaccine every 28 days is concerning. There have been no changes in recommendations from the CDC based on this study but it seems to make sense to consider getting our influenza vaccinations a bit later,  waiting until sometime in November, rather than rushing in to get one in August or September when the retail pharmacies start posting their signs. 

But Is It Just Baby Fat?
Childhood obesity continues into adolescence

Obesity is likely one of the largest problems facing our country and even the world. Researchers attempted to look at factors determining obesity in childhood along with determinants of obesity continuing into adolescence and adulthood. This study from The New England Journal of Medicine is a retrospective analysis of over 50,000 children from birth to 18 years of age. They found that most adolescents with normal weight had always had a normal weight throughout childhood, whereas 53% of obese adolescents had been overweight or obese since at least age 5. Almost 90% of 3 year old obese children became overweight or obese adolescents. Looking all the way back to birth weights, children born large for gestational age had a 55% increased chance of becoming overweight or obese adolescents as compared to normal weight or low weight babies. Obesity is occurring early in life and persisting to adolescence and will likely persist into adulthood.  



  • BACKGROUND: The dynamics of body-mass index (BMI) in children from birth to adolescence are unclear, and whether susceptibility for the development of sustained obesity occurs at a specific age in children is important to determine.
  • METHODS: To assess the age at onset of obesity, we performed prospective and retrospective analyses of the course of BMI over time in a population-based sample of 51,505 children for whom sequential anthropometric data were available during childhood (0 to 14 years of age) and adolescence (15 to 18 years of age). In addition, we assessed the dynamics of annual BMI increments, defined as the change in BMI standard-deviation score per year, during childhood in 34,196 children.
  • RESULTS: In retrospective analyses, we found that most of the adolescents with normal weight had always had a normal weight throughout childhood. Approximately half (53%) of the obese adolescents had been overweight or obese from 5 years of age onward, and the BMI standard-deviation score further increased with age. In prospective analyses, we found that almost 90% of the children who were obese at 3 years of age were overweight or obese in adolescence. Among the adolescents who were obese, the greatest acceleration in annual BMI increments had occurred between 2 and 6 years of age, with a further rise in BMI percentile thereafter. High acceleration in annual BMI increments during the preschool years (but not during the school years) was associated with a risk of overweight or obesity in adolescence that was 1.4 times as high as the risk among children who had had stable BMI. The rate of overweight or obesity in adolescence was higher among children who had been large for gestational age at birth (43.7%) than among those who had been at an appropriate weight for gestational age (28.4%) or small for gestational age (27.2%), which corresponded to a risk of adolescent obesity that was 1.55 times as high among those who had been large for gestational age as among the other groups.
  • CONCLUSIONS: Among obese adolescents, the most rapid weight gain had occurred between 2 and 6 years of age; most children who were obese at that age were obese in adolescence.


The rate of obesity in our society is rising rapidly. Seventy-one percent of adults are now overweight or obese. Even more concerning is the large rise in obesity in our children. This study followed over 50,000 children from birth to age 18 and had concerning findings. First, children who are obese at age 3 have a 90% chance of being overweight or obese adolescents! Secondly, babies born heavier (large for gestational age) were much more likely (55%) to be overweight or obese adolescents. Think about that, when a baby is born, it may already be at very high risk of obesity and the vast majority of overweight 3 year-olds are doomed to becoming overweight or obese teens. The most rapid weight gain was between 2 and 6 years of age so this is likely a good time to look at interventions and we also likely need to start to look at prenatal and preconception interventions. It appears high maternal insulin resistance (high insulin levels) is likely leading to insulin resistance in their babies, possibly leading to a lifetime of obesity and all of its associated health risks. 
Genetics + Inflammation = Dementia
Chronic inflammation along with genetic predisposition leads to higher risk of Alzheimer's Dementia
The researchers in this study used data from the Framingham Heart Study Offspring Cohort and examined the role of inflammation as a possible cofactor in the development of Alzheimer's dementia (AD). They had APOE status and c-reactive protein (CRP) information on each person in the trial and long-term follow up. APOE is an apolipoprotein mainly produced in the liver (but also produced in the brain) which  the helps with the transport and metabolism of cholesterol. There are three versions; E2, E3, and E4. We each have two copies. If you have two copies of E2 you have a 40% lower risk of developing Alzheimer's Dementia. However, if you have two copies of E4 you have a 10-15 times higher risk of developing AD. A single copy of APOE4 raises risk 3-4 times over the general population. Therefore APOE4 is a high risk marker for AD. The researchers then looked at the role of inflammation as a co-factor. They found that people with high levels of c-reactive protein (CRP), a surrogate for inflammation had a 6.6 times increased risk over those APOE4 carriers with low levels of CRP. Carriers of the APOE2 and APOE3 did not have higher levels of dementia even with high inflammation level. MRI scans done on those with high CRP and APOE4 found brain atrophy in the temporal lobe and hippocampus. It appears that chronic inflammation and genetic predisposition are needed for the development of Alzheimer's dementia. 


  • Importance: The association between peripheral inflammatory biomarkers and Alzheimer disease (AD) is not consistent in the literature. It is possible that chronic inflammation, rather than 1 episode of inflammation, interacts with genetic vulnerability to increase the risk for AD.
  • Objective: To study the interaction between the apolipoprotein E (ApoE) genotype and chronic low-grade inflammation and its association with the incidence of AD.
    Design, Setting, and Participants  In this cohort study, data from 2656 members of the Framingham Heart Study offspring cohort (Generation 2; August 13, 1971-November 27, 2017) were evaluated, including longitudinal measures of serum C-reactive protein (CRP), diagnoses of incident dementia including AD, and brain volume. Chronic low-grade inflammation was defined as having CRP at a high cutoff level at a minimum of 2 time points. Statistical analysis was performed from December 1, 1979, to December 31, 2015.
  • Main Outcomes and Measures: Development of AD and brain volumes.
  • Results: Of the 3130 eligible participants, 2656 (84.9%; 1227 men and 1429 women; mean [SD] age at last CRP measurement, 61.6 [9.5] years) with both ApoE status and longitudinal CRP measurements were included in this study analysis. Median (interquartile range) CRP levels increased with mean (SD) age (43.3 [9.6] years, 0.95 mg/L [0.40-2.35 mg/L] vs 59.1 [9.6] years, 2.04 mg/L [0.93-4.75 mg/L] vs 61.6 [9.5] years, 2.21 mg/L [1.05-5.12 mg/L]; P < .001), but less so among those with ApoE4 alleles, followed by ApoE3 then ApoE2 genotypes. During the 17 years of follow-up, 194 individuals (7.3%) developed dementia, 152 (78.4%) of whom had AD. ApoE4 coupled with chronic low-grade inflammation, defined as a CRP level of 8 mg/L or higher, was associated with an increased risk of AD, especially in the absence of cardiovascular diseases (hazard ratio, 6.63; 95% CI, 1.80-24.50; P = .005), as well as an increased risk of earlier disease onset compared with ApoE4 carriers without chronic inflammation (hazard ratio, 3.52; 95% CI, 1.27-9.75; P=.009). This phenomenon was not observed among ApoE3 and ApoE2 carriers with chronic low-grade inflammation. Finally, a subset of 1761 individuals (66.3%) underwent brain magnetic resonance imaging, and the interaction between ApoE4 and chronic low-grade inflammation was associated with brain atrophy in the temporal lobe (B = -0.88, SE = 0.22; P < .001) and hippocampus (B = -0.04, SE = 0.01; P = .005), after adjusting for confounders.
  • Conclusions and Relevance: In this study, peripheral chronic low-grade inflammation in participants with ApoE4 was associated with shortened latency for onset of AD. Rigorously treating chronic systemic inflammation based on genetic risk could be effective for the prevention and intervention of AD.
One of the major concerns of aging is the development of dementia. The incidence of dementia is rising rapidly around the world and we have all likely been touched by this horrible disease. We are learning more about the development of dementia, specifically Alzheimer's dementia. We have learned that people who carry the APOE4 apolipoprotein are at significantly higher risk. We don't fully understand why APOE4 leads to higher risk. In the general population, 8% have APOE2, 78% have APOE3 and 14% have APOE4. We can't change our genetic make up, so are we doomed to develop dementia? This study suggest the answer is no. Inflammation seems to be a necessary co-factor in the development of dementia. This study found that people who had APOE4 but low inflammation levels were at no higher risk of Alzheimer's overall than people with APOE2 or APOE3. This is great news! We aren't doomed by our genes. We can make lifestyle changes to reduce inflammation and thus reduce our risk of Alzheimer's dementia. This article discussed specific inflammatory and anti-inflammatory foods. There is some evidence that the statin medications may decrease risk of dementia which makes me wonder if this is due to the anti-inflammatory effects of this class of medications. 

Association of Chronic Low-Grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers JAMA Netw Open 2018 Oct 19;1(6)e183597.

Thank you for taking the time to read through this newsletter. I hope you have found this information useful as we work together to optimize your health. Feel free to pass this on to anyone you think would benefit from this information. 

You can find previous newsletters archived on my website here


As always, if you have questions about anything in this newsletter or have topics you would like me to address, please feel free to contact me by email , phone, or just stop by! 

To Your Good Health,
Mark Niedfeldt, M.D.