Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18(AV-45) positron emission tomography.

OBJECTIVE: To examine the association between regional brain uptake of a novel amyloid positron emission tomography (PET) tracer florbetapir F 18 ([(18)F]-AV-45) and cognitive performance in a pilot study. DESIGN: Cross-sectional comparison of [(18)F]-AV-45 in AD patients versus controls. SETTING: Three specialty memory clinics. PARTICIPANTS: Eleven participants with probable Alzheimer disease (AD) by NINDS/ADRDA criteria and 15 healthy comparison (HC) participants. MEASUREMENTS: Participants underwent PET imaging following a 370 MBq (10 mCi) intravenous administration of [(18)F]-AV-45. Regional/cerebellar standardized uptake value ratios (SUVRs) were calculated. Cognition was assessed using Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Wechsler Logical Memory IA (immediate recall) test (LMIA), and verbal category fluency. RESULTS: Greater [(18)F]-AV-45 SUVR was associated with poorer performance on all cognitive tests. In the HC group, occipital, parietal, precuneus, temporal, and cortical average SUVR was associated with greater ADAS-Cog, and greater anterior cingulate SUVR was associated with lower LMIA. Two HC participants had [(18)F]-AV-45 cortical/cerebellar SUVR greater than 1.5, one of whom had deficits in episodic recall and on follow-up met criteria for amnestic mild cognitive impairment. CONCLUSION: [(18)F]-AV-45 SUVR in several brain regions was associated with worse global cognitive performance particularly in HC, suggesting its potential as a marker of preclinical AD.

Fatty-acid amide hydrolase polymorphisms and post-traumatic stress disorder after penetrating brain injury.

The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-experiencing of trauma and more negative reported childhood experiences. In conclusion, our data suggest that FAAH has an important role in PTSD through modulation of aversive memories and point to both a novel therapeutic target and a possible risk marker for this condition.

Gustatory cortical lesions affect motivation for snack foods.

Most neuropsychological research using food as a reward uses single-bid auctions. We wished to determine whether focal brain lesions would affect the ability and motivation to win snack food items in a computerized auction allowing multiple bids. This allowed us to assess participants' abilities under more complex conditions. We enrolled 154 male penetrating traumatic brain injury (pTBI) veterans, mean age 58, from the Vietnam Head Injury Study registry, and 53 male uninjured veterans, mean age 59. We used voxel-based lesion symptom mapping (VLSM) to identify effects of brain lesions on the ability to win items and on participants' answers to statements regarding their level of motivation and evaluation of how well they performed. Number of items won was not significantly associated with any lesions; however, lesions in gustatory cortex (GC) affected motivation and self-evaluation. Our findings provide further evidence of the primary GC's role in motivation for food and drink.

Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury.

OBJECTIVE: This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI). METHODS: We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a). RESULTS: Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group. CONCLUSIONS: Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI.

Correlates of posttraumatic epilepsy 35 years following combat brain injury.

BACKGROUND: The Vietnam Head Injury Study (VHIS) is a prospective, longitudinal follow-up of 1,221 Vietnam War veterans with mostly penetrating head injuries (PHIs). The high prevalence (45%-53%) of posttraumatic epilepsy (PTE) in this unique cohort makes it valuable for study. METHODS: A standardized multidisciplinary neurologic, cognitive, behavioral, and brain imaging evaluation was conducted on 199 VHIS veterans plus uninjured controls, some 30 to 35 years after injury, as part of phase 3 of this study. RESULTS: The prevalence of seizures (87 patients, 43.7%) was similar to that found during phase 2 evaluations 20 years earlier, but 11 of 87 (12.6%) reported very late onset of PTE after phase 2 (more than 14 years after injury). Those patients were not different from patients with earlier-onset PTE in any of the measures studied. Within the phase 3 cohort, the most common seizure type last experienced was complex partial seizures (31.0%), with increasing frequency after injury. Of subjects with PTE, 88% were receiving anticonvulsants. Left parietal lobe lesions and retained ferric metal fragments were associated with PTE in a logistic regression model. Total brain volume loss predicted seizure frequency. CONCLUSIONS: Patients with PHI carry a high risk of PTE decades after their injury, and so require long-term medical follow-up. Lesion location, lesion size, and lesion type were predictors of PTE.