Table 4 Brain Imaging Studies of Patients With Hyperlipidemia, Without Symptomatic Cardiovascular, Cerebrovascular, and Peripheral Vascular
Disease
First
No. of
Subject Age, yrs,
Author
Treatment of
Study Design
Subjects
Mean (SD)
Imaging Modality
Imaging Findings
Hyperlipidemia
(Ref. #)
1. Higher serum total cholesterol levels
Reiman et
N = 117
al. (70)
55 apoE 4
Cross-sectional apo E4 noncarriers:
FDG PET: resting
were correlated with lower rCMRglu
state
bilaterally in the precuneus, prefrontal,
apoE 4 noncarriers,
18.5% receiving
59.8 (6.5)
noncarriers
statins
parietotemporal, and frontal regions.
apoE 4
Correlations remained significant after
heterozygotes:
controlling for statin use.
26.3% receiving
2. Slopes of the association between
statins
higher serum total cholesterol levels
apoE 4
and lower rCMRglu were greater in the
homozygotes: 37.5%
temporal cortex for each of the apoE ɛ4
receiving statins
carrier groups compared with the
apoE 4
38 apoE 4
heterozygotes, 60.5
heterozygotes
(43.9) apo E4
24 apoE 4
homozygotes, 58.7
homozygotes
(6.3)
noncarrier subjects.
1
N = 141
apo E4 noncarriers,
1. Structural MRI
70 apo E4
56.9 (4.6)
2. FDG PET: resting
noncarriers,
apo E4
42 apo E4
heterozygotes, 55.8
heterozygotes
(3.9)
29 apoE4
apo E4
homozygotes
homozygotes, 55.6
Reiman et
state
1. CREGS was correlated with lower
al. (71)
Calculation of each
regional to whole-brain PET
Treatment data not
subject’s CREGS
Cross-sectional
measurements of rCMRglu in the
available.
was based on a
posterior cingulate, precuneus,
cluster of
(5.1)
parietotemporal, and frontal regions.
polymorphisms
associated with
Alzheimer’s disease.
Sinha et
19
With
Group 1: 13
1. 1H MRS
1. In the combined hyperlipidemic and
with
hyperlipidemia, 32.6
hyperlipidemic
2. SPECT
normolipidemic groups, the Cho/Cr
hyperlipidemia
(6)
subjects receiving
ratio in the occipital region was high in
Cross-sectional
al. (65)
21
Without
HMG-CoA reductase
subjects with excess percentage of body
without
hyperlipidemia, 29.8
inhibitor treatment.
fat.
hyperlipidemia
(4.5)
2. In the combined hyperlipidemic and
2
Group 2: 6
normolipidemic groups, the Cho/Cr
hyperlipidemic
ratio in the occipital region was low in
subjects not
subjects with low HDL-C.
receiving statin
3. In the combined hyperlipidemic and
treatment.
normolipidemic groups, the NAA/Cho
Group 3: 21
ratio in the occipital region was low in
normolipidemic
subjects with high total cholesterol and
subjects.
non–HDL-C levels.
4. 50% of subjects with
hypertriglyceridemia demonstrated
temporal hypoperfusion compared with
14% of subjects with normal
triglyceride levels.
1. Higher LDL and total cholesterol
41 receiving lipidReceiving lipid-
were associated with lower FA values
lowering
in the right hemisphere. The most
lowering
medication
medication, 71.29
83 not receiving
Williams
robust associations occurred in frontal
33% of subjects
(7.83)
lipid-lowering
et al. (69)
1. Structural MRI
and temporal regions. LDL emerged as
2. DTI MRI
the most robust predictor of white
Cross-sectional receiving lipidNot receiving lipid-
medication
lowering medication.
lowering
matter tissue integrity as indexed by
medication, 66.37
FA.
(9.78)
2. Negative associations between HDL
and FA were also mainly lateralized to
3
the right hemisphere and included
sections of the anterior limb of the
internal capsule, the external capsule,
thalamic pathways, and frontal regions.
3. Triglyceride levels revealed the
fewest voxels showing significant
associations with FA, including the
genu of the corpus callosum.
4. Radial diffusivity qualitatively held
greater associations with LDL in more
anterior white matter regions, and axial
diffusivity exhibited larger associations
with LDL in posterior regions.
5. No significant group differences in
mean FA between medication groups
for all significant clusters.
5 with
With homozygous
100% of subjects
homozygous
familial
familial
No white matter lesions in any of the
hypercholesterolemia
subjects in either group and no other
hypercholesterolemi
Schmitz et
hypercholesterole
with familial
a, 23.4 (9.2)
al. (66)
mia
Without familial
5 without familial
hypercholesterolemi
hypercholesterole
a, 27.8 (3.2)
Cross-sectional
Structural MRI
being treated with
abnormality was identified in either
HMG-CoA reductase
group.
inhibitors.
4
mia
1. 16% of subjects with heterozygous
familiar hypercholesterolemia and 24%
of subjects without familial
hypercholesterolemia had ≥1 WMH.
39 with
With heterozygous
heterozygous
familial
72% of subjects with
familial
hypercholesterolemi
heterozygous
No statistical difference in occurrence
of WMHs between subjects with
familiar hypercholesterolemia and
Soljanlahti hypercholesterole
a, 30.0 (13.6)
familial
1. Structural MRI
Cross-sectional
et al. (68)
mia
Without familial
subjects without familial
hypercholesterolemia 2. MR angiography
hypercholesterolemia.
25 without familial hypercholesterolemi
were receiving statin
2. The mean intima-media thickness of
hypercholesterole
a, 30.6 (11.3)
medication.
the far wall of the left common carotid
mia
artery was greater in the subjects with
familiar hypercholesterolemia
compared with subjects without
familial hypercholesterolemia.
1. Lower gray matter volume was
Whalley et
Treatment data not
N = 82
al. (64)
Age, 78.5
Cross-sectional
associated with higher total cholesterol
Structural MRI
available.
and LDL.
2. Cerebrospinal fluid volume
5
positively correlated with total
cholesterol and LDL.
3. No association between white matter
volume and total cholesterol.
14 with
With heterozygous
No significant difference in the
100% of subjects
heterozygous
familial
proportion of subjects with and without
with heterozygous
familial
hypercholesterolemi
familial hypercholesterolemia with
familial
Schmitz et
hypercholesterole
a, 39 (10)
WMHs: WMH was observed in 3 of 22
Cross-sectional hypercholesterolemia Structural MRI
al. (67)
mia
Without familial
subjects without familial
being treated with
22 without familial hypercholesterolemi
hypercholesterolemia and in 1 of 14
lipid-lowering
hypercholesterole
a, 41 (12)
with heterozygous familial
medication.
mia
hypercholesterolemia.
apo = apolipoprotein; CREGS = cholesterol-related genetic score; FDG = fluorodeoxyglucose; HDL-C = high-density lipoprotein cholesterol; HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LDL = low-density
lipoprotein; MR = magnetic resonance; other abbreviations as in Tables 2, 3, and 5.
6