(NINCDS-ADRDA) crite ria for possible or probable AD
(McKhann et al., 1984). The sub jects were assessed with the
Clinical De mentia Rating (CDR) s core [26], CDR of 1 and 2
was assigned to the AD category.
Participants with MCI had memory impairment but did not
meet the criteria for dementia. T he criteria for identification
and classification of subjects with MCI [27] was: a) impaired
memory perfor mance o n a normalized objectiv e verb al
memory test; b) recent history of symptomatic worsening in
memory; c) normal or near-normal performance on global
cognitive te sts (MM SE scor e.24),aswellasonanactivitiesof
daily l iving scale; (d) global rating of 0.5 on the CDR Scale,
with a score of at least 0.5 on the memory domain; e) absence
of dementia.
Healthy controls met the following criteria: a) no neurological or
psychiatric disorders such as stroke, depression and epilepsy; b) no
neurological deficiencies such as visual or hearing loss; c) no
abnormal findings such as infarction or focal lesion in conventional
brain MR imaging; d) no cognitive complaints; e) MMSE score of
28 or higher; f) CDR score of 0.
Participants with contraindications for MRI such as pacemaker,
cardiac defibrillator, implanted material with electric or magnetic
system, vascular clips or mechanical heart valve, cochlear implant
or claustrophobia were excluded. In addition, patients with a
history of stroke, psychiatric diseases, drug abuse, severe hyper-
tension, systematic diseases and intellectual disability were
excluded.
Data acquisition
MRI d ata acquisition was performed on a SIEMENS verio
3-Tesla scanner (Siemens, Erlangen, Germany). The subjects
were instructed to hold still, kee p eyes closed and think nothing
in particular. fMRI was acquire d axially using an echo-planar
imaging (EPI) [repetition time (TR)/echo time (TE)/flip angle
(FA)/field of view (FOV) = 2000 ms/40 ms/90u /24 cm,
image matrix = 64664, slice number = 33, thickness = 3 mm,
gap = 1 mm, bandwidth = 2232 Hz/pixel]. In addition, 3D T
1
-
weighted magne tization-prepared rapid gradient echo
(MPRAGE) sagittal images were obtained (TR/TE/inver-
sion time (TI)/FA = 1900 ms/2.2 ms/900 ms/9u , image ma-
trix = 2566256, slice number = 176, thickness = 1 mm).
Our study used a single block experimental design. We first
acquired the baseline resting state data in the initial 3 minute s;
we then acquired the fMRI data during the procession of
acupuncture stimulation for the following 3 minutes. A silver
needle of 0.30 mm in dia meter and 25 mm long was inserted
and twirled at t he four acupoints of the human body -Tai
chong (Liv3) on the dorsum of the left and right foot; He gu
Table 2. Regions showing increased or decreased activities in MCI, AD subjects comparing to normal subjects in resting state.
Regions BA
Cluster Coordinates (MNI)
T-score
Size x y z
MCI vs. NOR
Lt. Middle Temporal Gyrus q 39 16 257 267 13 3.94
Rt. Inferior Frontal Gyrusq 44 127 60 5 16 5.46
Lt. Middle Frontal Gyrus q 68 233 14 61 4.05
Lt. Middle Frontal Gyrus q 10 19 239 59 7 3.78
Rt. Inferior Frontal Gyrus q 45 6 57 29 7 3.64
Lt. Inferior Frontal Gyrusq 46 7 248 47 4 3.37
Lt. Superior Frontal Gyrusq 10 12 218 62 25 3.30
Lt. Superior Frontal Gyrusq 616 215 23 64 3.15
Lt. Lentiform Nucleusq -6 215 2 25 3.28
Rt. Cingulate GyrusQ -16 12 2428 23.19
Lt. Fusiform GyrusQ 20 6 230 237 223 23.15
AD vs. NOR
Lt. Temporal Lobe Q 20 45 242 219 217 24.11
Lt. Middle Frontal GyrusQ 11 12 236 50 214 23.19
AD vs. MCI
Lt. Middle Temporal LobeQ 21 22 248 234 22 24.87
Lt. Middle Temporal LobeQ 21 8 254 5 223 23.55
Lt. Inferior Parietal lobuleQ 40 54 260 249 43 23.89
Lt. Middle Frontal Gyrus Q 11 29 230 35 214 23.54
Rt. Precentral gyrus Q 68 63 2131 23.34
Lt. Frontal Sub Gyral Q -9 212 20 28 23.24
Lt. Superior Frontal GyrusQ 86 233 20 58 23.08
doi:10.1371/journal.pone.0042730.t002
Acupuncture in MCI and AD
PLOS ONE | www.plosone.org 3 August 2012 | Volume 7 | Issue 8 | e42730