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Journal Club
Julie Shah, MD
Milton S Hershey Medical Center
Penn State University
Memory in Diabetes sub study embedded in the Action to
Control Cardiovascular risks in Diabetes ( ACCORD)
Background
♥ Elderly patient with T2Dm have at least twice
the likelihood of developing late-life cognitive
impairment or dementia
♥ Possible mechanisms involve vascular,
neurodegenerative or neurovascular processes
Hypothesis
♥ At 40- months, patients randomized to receive
intensive glycemic treatment strategy
(targeting HbA1c of < 6.0%) would have a
better cognitive function and larger brain
volume than patients randomized to receive
standard strategy targeting HbA1c 7.0- 7.9%
♥ Participants from ACCORD trial were eligible
for the MIND study if they were recruited
between Aug 2003 and Dec 2005.
♥ Excluded patients < 55yr of age and
participants form VA network
♥ Additionally, within MIND a subset of
participants were recruited for the MRI
substudy
Methods
♥ Intensive glycemic grouptreatment target HbA1c <6%
started on 2 or more classes of antiglycemic
medications and new drug was added monthly if
HbA1c was > 6%
♥ Standard treatment grouptreatment target HbA1c 7.0-7.9%
Treatment was intensified if HbA1c >8%
Methods
♥ Battery of cognitive tests were administered at baseline, 20
months and 40 months after randomization.
♥ Primary cognitive outcome was Digital symbol substitution
test (DSST)- test psychomotor speed, reasoning and memory
♥ Secondary cognitive outcomesRey auditory verbal learning test (RAVLT)- measures
memory
Stroop test- executive functioning
♥ MRI cohort- Brain MRI performed at baseline and 40-months
with primary endpoint as Total brain volume (TBV) and
secondary outcome Abnormal white matter (AWM)- indicates
ischemic, demyelinating or inflammatory processes
Digit Symbol Substitution Test
Results
2977 enrolled for MIND study
Intensive intervention = 1469
1378 completed study
Standard intervention = 1508
Total 2794
1416 completed study
632 participants eligible for MRI substudy
Intensive intervention = 301
230 completed study
Standard intervention = 331
273 completed study
♥ In Feb 2008, the intensive intervention arm
was stopped due to increased risk for mortality.
♥ These pts were moved to the standard
treatment arm. By then pts in cognitive study
had received treatment for median of
39months and MRI substudy had received
treatment for 35 mo
6.6%
7.5%
Results
0.41%
0.57%
Discussion
♥ Overall, there is NO evidence to suggest that
intensive glycemic treatment strategies provide
benefit to cognitive function.
♥ There is a small difference in TBV favoring intensive
treatment; however, ACCORD trial suggested that
there was increased mortaltity, no overall
cardiovascular benefit, increased risk of
hypoglycemia and weight gain
♥ It is possible that optimal diabetes care provided to all
pts may have brought glucose down to sufficient
control which may have thus attenuated treatment
difference in cognitive scores.
♥ Taking cognitive and MRI finding together, it
may be reasonable to postulate that structural
changes occur before cognitive changes and
that over time cognitive differences between
treatment groups may emerge.
♥ With additional followup of this cohort we will
be able to establish if different treatment
strategies result on different rates of cognitive
changes.