Widespread Decrease of Type 1 Cannabinoid Receptor Availability in Huntington Disease In Vivo

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FIGURE 1.
Cross-sectional, partial-volume corrected, modified standardized uptake value (mSUV) parametric images, averaged for all controls (n = 14), early-HD patients (n = 7), and total group of HD patients (n = 19).
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FIGURE 2.
Bar chart of regional differences in CB1 availability (¹⁸F-MK-9470 binding) between HD and controls after partial-volume correction. ***P < 0.001 vs. controls. Mes temp = mesial temporal; mSUV = modified standardized uptake value; n.s. = not significant. Error bars indicate 1 SD.
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FIGURE 3.
Surface rendering of voxel-based correlation between absolute CB1 availability and disease burden ([(CAG)_n – 35.5] × age) at peak height threshold P_height < 0.005 (uncorrected). Clusters are overlaid on surface-rendered average image of HD patients.

TABLE 1.

Demographic and Clinical Characteristics of Subjects

	HD
Parameter	All (n = 20)	Early (n = 7)	Control (n = 14)
Sex (n)
M	8	3	6
F	12	4	8
Age (y)	53.3 ± 12.1 (32.3–83.1)	47.3 ± 11.6 (32.3–64.5)	54.3 ± 12.9 (30.7–68.5)
Weight (kg)	65.9 ± 11.1 (50.0–89.0)^*	71.7 ± 9.9 (60.0–89.0)	75.7 ± 10.6 (58.0–95.0)
(CAG)_n	43.6 ± 2.8 (39–50)	44.3 ± 3.9 (40–50)	—
Estimated disease duration (y)	6.0 ± 5.5 (0.5–19.4)	1.9 ± 1.5 (0.5–4.5)	—
UHDRS motor score	35.2 ± 25.0 (8–80)	15.0 ± 6.1 (8–27)	—
UHDRS TFC score	6.4 ± 4.8 (0–13)	11.9 ± 0.9 (11–13)	—
Shoulson–Fahn stage			—
I	7	7
II	3	0
III	4	0
IV	4	0
V	2	0
Handedness
L	2	0	3
Ambidexter	0	0	1
R	18	7	10

↵* Significant difference between patients and controls (P < 0.05).
Values represent mean ± SD, with range in parentheses. UHDRS motor scale ranges from 0 to 124, with higher scores indicating more motor impairment. UHDRS TFC scale assesses ability to perform daily activities and ranges from 13 (no impairment) to 0 (total incapacity). TFC scores are further subdivided into 5 Shoulson–Fahn stages: I (representing TFC scores 11–13), II (scores 7–10), III (scores 3–6), IV (scores 1–2), and V (score 0).

TABLE 2.

Volumetric Cerebral and Striatal Data in HD Patients Versus Controls

Parameter	HD (n = 19)	Control (n = 14)
Gray-matter volume (relative to intracranial volume)	0.447 ± 0.031^*	0.474 ± 0.018
White-matter volume (relative to intracranial volume)	0.248 ± 0.033	0.273 ± 0.016
Cerebrospinal fluid volume (relative to intracranial volume)	0.305 ± 0.041^*	0.253 ± 0.019
Mean caudate volume^† (cm³)	1.13 ± 0.47^‡	3.69 ± 0.35
Mean putamen volume^† (cm³)	1.54 ± 0.68^‡	3.78 ± 0.55