Longitudinal 18F-FDG Images in Patients With Alzheimer Disease Over More Than 9 Years From a Preclinical Stage.

BACKGROUND: Brain F-FDG uptake reportedly starts to decline more than 10 years before the onset of cognitive decline in dominantly inherited Alzheimer disease (AD). We compared longitudinal F-FDG images in sporadic AD to aging data from a large sample size to expand the current knowledge of F-FDG reduction for AD progression. METHODS: Participants comprised 2 individuals (subjects A and B at ages 65 and 68 years, respectively) and 107 control subjects (67.9 [SD, 4.9] years). Subject A underwent F-FDG PET a total of 8 times over 9 years from the preclinical to early dementia stages. Subject B underwent F-FDG PET a total of 11 times over 12 years from the preclinical to mild cognitive impairment stages. Control subjects underwent F-FDG PET twice over a mean follow-up period of 7.8 years. After placing the volume of interest on the AD-related hypometabolic regions, the longitudinal F-FDG images were compared among the subjects and control subjects. RESULTS: For the control group, the rate of F-FDG reduction was 2.2% per decade (ie, aging effects). The rates of F-FDG reduction were 9.41% over 9 years and 9.07% over 12 years in subjects A and B, respectively. We estimated that F-FDG uptake started to decrease 4 and 2 years before indications of memory loss in subjects A and B, respectively. CONCLUSIONS: The present study suggests that the time between the beginning of F-FDG reduction and the onset of cognitive decline may be shorter in elderly individuals with AD compared with the recently estimated period in dominantly inherited AD.

Neural substrate of a cognitive intervention program using Go game: a positron emission tomography study.

BACKGROUND: Influence of cognitive intervention programs on brain activity has not been enough explored. AIMS: The aims of the present study were to clarify changes in brain activity from a cognitive intervention program utilizing the board game "Go" and to examine the relationship between brain activity and the acquisition of Go skills. METHODS: Eighteen community-dwelling older adults were randomly assigned either to an intervention group (IG), in which members attended 12 Go lessons either in groups or individually using tablet computers, or a control group (CG), in which members attended health education lectures unrelated to Go. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), cognitive assessments, and Go tests were performed before and after the intervention. RESULTS: The results showed different patterns of regional FDG uptake in both groups: regional cerebral glucose metabolism was significantly increased in the left middle temporal gyrus (MTG) and bilateral putamen (p < 0.01; cluster level) in the IG, and in the left superior frontal gyrus in the CG, (p < 0.01; cluster level). Furthermore, Go test scores were significantly improved in the IG (p < 0.05), and a significant association was observed between changes in Go test scores and glucose metabolism in the left MTG (p < 0.05). CONCLUSIONS AND DISCUSSION: This study indicates that a cognitive intervention program using Go may enhance brain activity. Further studies with larger populations and longer observation periods are needed to clarify the neural mechanisms underlying our Go intervention program.

Longitudinal effects of aging on 18F-FDG distribution in cognitively normal elderly individuals.

Previous studies of aging effects on fluorine-18-labeled fluorodeoxyglucose (18F-FDG) distribution have employed cross-sectional designs. We examined aging effects on 18F-FDG distribution using both cross-sectional and longitudinal assessments. We obtained two 18F-FDG positron emission tomography scans at two different time points from 107 cognitively normal elderly participants. The participants' mean ages at baseline and second scans were 67.9 and 75.7, respectively. The follow-up period ranged from 4 to 11 years with a mean of 7.8 years. The voxel-wise analysis revealed significant clusters in which 18F-FDG uptake was decreased between baseline and second scans (p < 0.05, family-wise error corrected) in the anterior cingulate cortex (ACC), posterior cingulate cortex/precuneus (PCC/PC), and lateral parietal cortex (LPC). The cross-sectional analysis of 18F-FDG uptake and age showed significant correlations in the ACC (p = 0.016) but not the PCC/PC (p = 0.240) at baseline, and in the ACC (p = 0.004) and PCC/PC (p = 0.002) at the second scan. The results of longitudinal assessments suggested that 18F-FDG uptake in the ACC, PCC/PC, and LPC decreased with advancing age in cognitively normal elderly individuals, and those of the cross-sectional assessments suggested that the trajectories of age-associated 18F-FDG decreases differed between the ACC and PCC/PC.

Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects.

BACKGROUND: Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. METHODS: Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. RESULTS: Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 µU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05), and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4-5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). CONCLUSION: This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images.

Plasma Glucose Levels Affect Cerebral 18F-FDG Distribution in Cognitively Normal Subjects With Diabetes.

PURPOSE: Increased plasma glucose levels can relatively reduce F-FDG uptake in Alzheimer disease (AD)-related regions and alter the cerebral distribution pattern of F-FDG, resulting in the appearance of an AD-like pattern. However, the relationship between the reversibility of the AD-like pattern and plasma glucose levels is uncertain. METHODS: Four cognitively normal elderly subjects with diabetes underwent longitudinal F-FDG PET more than 5 times at various levels of plasma glucose. F-FDG data were proportionally scaled with a global normalization method and used in volume of interest-based and voxelwise analyses. Volumes of interest were placed on representative AD-related regions: precuneus/posterior cingulate (PP), lateral parietal cortex, and frontal cortex. RESULTS: Volume of interest-based analyses showed negative correlations of plasma glucose levels with F-FDG uptake in the PP (r = -0.79, P < 0.001), lateral parietal cortex (r = -0.62, P = 0.002), and frontal cortex (r = -0.73, P < 0.001), controlling for the effects of interindividual differences and age. Voxelwise analyses also showed negative correlations between the 2 factors in the PP and medial frontal areas (P < 0.05, familywise error rate corrected). CONCLUSIONS: This study indicates that the distribution pattern of F-FDG changes depending on plasma glucose levels in an individual and that the AD-like pattern can appear or disappear with increasing or decreasing plasma glucose levels, respectively.

Relationship between Alzheimer disease-like pattern of 18F-FDG and fasting plasma glucose levels in cognitively normal volunteers.

UNLABELLED: Increased plasma glucose (PG) levels can alter the cerebral distribution pattern of (18)F-FDG uptake and reduce (18)F-FDG uptake, especially in the precuneus. The (18)F-FDG distribution pattern in cognitively normal subjects is described as an Alzheimer disease (AD)-like pattern. The aim of this study was to determine the fasting PG levels that can reduce (18)F-FDG uptake in the precuneus. METHODS: Fifty-one cognitively normal volunteers (mean age ± SD, 69.7 ± 5.9 y) underwent (18)F-FDG PET scanning and were divided into 2 groups according to the level of fasting PG at the time of PET scanning: control (n = 31, 80 mg/dL ≤ fasting PG < 100 mg/dL) and impaired fasting glucose (IFG) (n = 20, 100 mg/dL ≤ fasting PG < 110 mg/dL). (18)F-FDG uptake was compared between the 2 groups using voxelwise analyses with a global normalization method and volume-of-interest (VOI)-based analyses. VOIs were placed on the precuneus, posterior cingulate, and visual cortex, and the ratio of the uptake value on the precuneus VOI to that on the visual cortex VOI (PreCne/VC ratios) and to that on the posterior cingulate VOI (PreCne/PostCin ratios) was calculated. RESULTS: Whole-brain voxelwise analyses showed that (18)F-FDG uptake in the precuneus was significantly lower in the IFG group (P < 0.05, familywise error rate-corrected) than in the control group. VOI analyses showed significantly lower PreCne/VC ratios (P = 0.002) and PreCne/PostCin ratios (P = 0.004) in the IFG group than in the control group. CONCLUSION: The present study confirmed that increased fasting PG levels decrease (18)F-FDG uptake, especially in the precuneus, as in the AD-like pattern. Furthermore, the study provided initial evidence that the AD-like pattern can appear even in an individual with a mildly higher level of fasting PG (100-110 mg/dL).