3: Luke Spong

A. 1st ,2nd and 3rd Authors

C. L. Leibson 1
W. A. Rocca 1,2
V. A. Hanson 1,3
B. Authors Affiliation
1
Department of Health Sciences Research, Mayo Clinic/Foundation, Rochester, MN.
2
Department of Health Sciences Research, Mayo Clinic/Foundation, Rochester, MN.
3
Department of Health Sciences Research, Mayo Clinic/Foundation, Rochester, MN.
C. Article Citation
Leibson, C., Rocca, W., Hanson, V., Cha, R., Kokmen, E., O'brien, P., & Palumbo, P. (1997).
Risk of Dementia among Persons with Diabetes Mellitus: A Population-based Cohort Study.
American Journal of Epidemiology, 145(4), 301-308.
D. Rationale and Purpose of the Study
Dementia is a disease that effects the brains cognitive ability to function properly, thus
resulting in decreased motor skills and cognitive thinking. In relation, diabetes mellitus affects
the bodies ability to maintain a homeostasis level, thus resulting in a loss of motor control,
neurological function of the extremities and the metabolic function. This study focuses on how
the two diseases may be linked. Prior studies have found that it is somewhat unclear whether a
person with diabetes mellitus is at risk for dementia and/or Alzheimer's disease. Most prior
studies have, however, been extremely limited in the sample size and the variabilities that factor
into the researched population. There considerable research that links types of dementia and
Alzheimer's with diabetes due to the insulin sensitivity, of which effects the neurological system.
A particular study was performed to monitor the brain function of those with diabetes and
dementia 3. What they found was that the brain was far less capable of regulating oxygen and
blood flow 3. This supporting research can be compared and factored into the cohort study being
reviewed as followed. The purpose of this study is to identify the relationship between dementia,
Alzheimer's and diabetes. However, there have been other studies that are more up to date that
suggest there is a direct relationship between these three diseases. The issue is, researchers have
been unable to understand what cognitive functions that diabetes will effect within the body,
particularly the brain 1. Another linked study suggests that diabetes alters the mitochondrial
ability within the brain 3.
E. Summary of the Research Design
The research design for this particular researched followed that of cohort study
characteristics. A prospective summary can be found during the first two paragraphs of the
article. Additional data is displayed in tables and graphs within the text.
F. Description of Participants
Participants within this study were already a population based out of Rochester, MN.
This research identified all of the diabetes incidence from 1970-1984, with prevalence groups
(23-25). The inclusion criteria for diabetes mellitus were those outline by the National Diabetes
Group (26). The inclusion criteria was as followed: Rochester residents; two consecutive fasting

glucose levels >140 mg/dl, or 1 and 2 hour levels >200 mg/dl. These results for the inclusion
criteria would be gathered by a standard oral glucose tolerance test. People who failed to meet
the criteria for the criteria above, but still remained clinically dependent on oral agents or insulin
for proper homeostasis, still was considered a case within the study. If a resident moved to
Rochester with diagnosed diabetes, they were placed in the first incident cohort of January 1,
1980. The exclusion criteria was as listed as followed: those who did have diabetes mellitus,
though were not in the adult onset stage (20 years or older). There was discussion about
excluding insulin dependent, or non-insulin dependent, though this was later decided to be
classified into two groups 1.
The last inclusion criteria was for those who had dementia. After careful consideration,
they excluded those with non-Alzheimer's like symptoms. Exclusion was also taken further into
removing cases that had onset of dementia before the start the experiment were removed 1.
G. Summary of Data Collection Methods
The association that diabetes and dementia share was estimated using two separate
approaches. The first approach looked at the observed rates of dementia (and Alzheimer's
disease) within the population, and compared them to persons with ADOM with expected rates.
To estimate a comparative timeline for both observed and expected rates, the cohort study only
looked at January 1, 1970- December 31, 1984 incident cases. Prevalence cases diagnosed
elsewhere, but moved to Rochester were placed into the January 1, 1980 or 1990 group.
Individuals were then followed until they showed signs of their earliest onset of dementia, date
last seen, death, or until January 1, 1985. The calculation of expected rates, each age group over
or at 85 years of age was then classified into age groups by every 5 years margin. The effects of
age and gender were statistically calculated within the equations. This accounted for the
observed vs. expected outcome morbidity ratios 1.
Following the first approach, the second approach was purely statistical while using
Poisson regression to calculate the risk of dementia and Alzheimer's for person with AODM
compared to those without AODM. The data for this approach was used by having several
different combinations of gender, age, calendar year, and if AODM was prevalent. The subjects
were placed into a strata and observed over time. As time progresses, the denominator increase
from human subject years in the study. This was then compared to the severity and incident rate
within that calendar year. Then a calculation was formulated using the statistics found above.
The variables were entered into the regression model in linear fashion 1.
H. Summary of Major Results
This cohort study used 1,455 persons with a combined total of 9,981 person years. There
was a range set from 0-15. "0" meaning the subject did at diagnosis of diabetes and so forth.
Only 101 subjects met the criteria for dementia and only seventy seven of the 101 met the
criteria for Alzheimer's. As age increased in Rochester, the incidence increased with those over
the age of 99, and between 80-89 with those that have AODM. Those who had dementia were
classified as having either non-Alzheimer's, Alzheimer's, or Alzheimer's followed by another
form of dementia did not differ in a significant fashion between the AODM cohort (24, 58 and
18 percent) and the Rochester cohort (21, 66, and 13 percent)1.
The standardized morbidity ratio for both sexes with dementia was 1.60 with a
confidence interval of 95%. The standardized morbidity ratio for both sexes with Alzheimer's
disease was 1.59, with a confidence interval of 95% 1.

In the second data collection approach, Poissons regression was used to evaluate the
sudden and long term effects of age, gender, presence of diabetes, and calendar year. For those
with AODM, there was 1.66 times greater risk of dementia for persons without AODM. The
associated between both diabetes and dementia did not depend on age (p = 0.52 for age by
diabetes interaction). For Alzheimer's disease calculated gender, calendar year in addition to age
and diabetes. The effects of age and the calendar year proved to be non-linear. Essentially, this
trend showed that there is a rise in the Alzheimer\'s disease is the upper age groups. For men
with diabetes they are at twice the risk for Alzheimer's than those without diabetes. Relative risk
= 2.27; 95% confidence interval 1.
I. Discussion of Practical Importance and Implications of Major Results
This study was the first population based study that looked at the relationship between
dementia, Alzheimer's and diabetes. The risk of dementia was both elevated for both genders
that had AODM compared to those without AODM. I believe that it is somewhat safe
acknowledge that there is a relationship, though further testing should be completed for better
understanding of the two diseases. A more up to date study tested the functions of the brain
with person that had diabetes 2. This testing concluded that a subset group that has dementia
may underlie those with a neuropathological disorder. This research also challenged that
persons that AODM and dementia are at a much higher risk level for impaired glucose
tolerance than those with only one of the diagnosed diseases. In parallel with his statement,
those with AODM and dementia also face a higher risk of insulin sensitivity, thus affecting the
participant more. The limitations of this study included: lack of description regarding type I
and type II diabetes; which subsets of dementia were more affected; many stratas were evident
even though the research population was large. Some of the strengths observed were: two types
of statistical analysis were performed which relied on the other for data support, in depth data
was given, researchers had clear and concise inclusion and exclusion criteria; the population
observed was large compared to last studies.
In summary, this study revealed a significant increase of the risk involved with dementia
for persons with AODM and challenged the hypothesis that a person with AODM is protective
for Alzheimer's disease. These association made evident in the study could be normal, or they
could be from a predisposed genetic sequence. Further testing on the subject matter would
benefit the topic in a variety of ways.
Reference Sheet:
2) Fukasawa, R., Hanyu, H., Shimizu, S., Kanetaka, H., Sakurai, H., & Ishii, K. (2015).
Identification of diabetes-related dementia: Longitudinal perfusion SPECT and amyloid
PET studies. Journal Of The Neurological Sciences, 349(1/2), 45-51.
doi:10.1016/j.jns.2014.12.023
3) Naoyuki, S., & Ryuichi, M. (2014). Brain alterations and clinical symptoms of
dementia in diabetes: A/tau-dependent and independent mechanisms. Frontiers In
Endocrinology, 51-8. doi:10.3389/fendo.2014.00143