Molly E. Zimmerman

BACKGROUND: The neuropathogenesis of bipolar disorder remains poorly described. Previous work suggests that patients with bipolar disorder may have abnormalities in neural pathways that are hypothesized to modulate human mood states. We examined differences in brain structural volumes associated with these pathways between patients with bipolar disorder hospitalized with mania and healthy community volunteers. METHODS: Twenty-four patients with bipolar disorder and mania were recruited from hospital admission records. Twenty-two healthy volunteers were recruited from the community who were similar to the patients in age, sex, race, height, handedness, and education. All subjects were scanned using a 3-dimensional radio-frequency-spoiled Fourier acquired steady state acquisition sequence on a 1.5-T magnetic resonance imaging scanner. Scans were analyzed using commercial software. Prefrontal, thalamic, hippocampal, amygdala, pallidal, and striatal volumetric measurements were compared between the 2 groups. RESULTS: Patients with bipolar disorder demonstrated a significant (A = 0.64; F6,37 = 3.4; P = .009) overall difference in structural volumes in these regions compared with controls. In particular, the amygdala was enlarged in the patients. Brain structural volumes were not significantly associated with duration of illness, prior medication exposure, number of previous hospital admissions, or duration of substance abuse. Separating patients into first-episode (n = 12) and multiple-episode (n = 12) subgroups revealed no significant differences in any structure (P>.10). CONCLUSION: Patients with bipolar disorder exhibit structural abnormalities in neural pathways thought to modulate human mood.

OBJECTIVE: White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. METHODS: The study comprised participants (n = 299; age = 39.03 ± 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. RESULTS: Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. INTERPRETATION: Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929-939.

SUMMARY: The past decade has seen an increase in the number of articles reporting the use of DTI to detect brain abnormalities in patients with traumatic brain injury. DTI is well-suited to the interrogation of white matter microstructure, the most important location of pathology in TBI. Additionally, studies in animal models have demonstrated the correlation of DTI findings and TBI pathology. One hundred articles met the inclusion criteria for this quantitative literature review. Despite significant variability in sample characteristics, technical aspects of imaging, and analysis approaches, the consensus is that DTI effectively differentiates patients with TBI and controls, regardless of the severity and timeframe following injury. Furthermore, many have established a relationship between DTI measures and TBI outcomes. However, the heterogeneity of specific outcome measures used limits interpretation of the literature. Similarly, few longitudinal studies have been performed, limiting inferences regarding the long-term predictive utility of DTI. Larger longitudinal studies, using standardized imaging, analysis approaches, and outcome measures will help realize the promise of DTI as a prognostic tool in the care of patients with TBI.

OBJECTIVES: To conduct a systematic clinical and quantitative assessment of gait in older adults with mild cognitive impairment (MCI) syndromes. DESIGN: Cross-sectional. SETTING: Einstein Aging Study, a community-based longitudinal aging study. PARTICIPANTS: Fifty-four individuals with amnestic MCI (a-MCI), 62 with nonamnestic-MCI (na-MCI), and 295 healthy controls identified from the Einstein Aging Study participants. MEASUREMENTS: Comparison of clinical and quantitative gait performance in subjects with MCI subtypes with that of cognitively normal older adults. RESULTS: Neurological gaits were more common in a-MCI (31.5%, P=.008) but not in na-MCI (19.4%, P=.55), than in controls (16.3%). Quantitative gait in multiple parameters was worse in both MCI subtypes than in controls. Factor analysis revealed three independent factors representing pace, rhythm, and variability. Subjects with a-MCI had worse rhythm and variability scores than those with na-MCI and controls. Subjects with na-MCI had worse performance on the pace domain than the other two groups. Subjects with MCI and gait abnormalities had higher disability scores than subjects with MCI without gait abnormalities. CONCLUSION: Gait dysfunction is common in older individuals with amnestic and nonamnestic subtypes of MCI.

As the population ages, the need to characterize rates of cognitive impairment and dementia within demographic groups defined by age, sex, and race becomes increasingly important. There are limited data available on the prevalence and incidence of amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI) from population-based studies. The Einstein Aging Study, a systematically recruited community-based cohort of 1944 adults aged 70 or older (1168 dementia free at baseline; mean age, 78.8 y; average follow-up, 3.9 y), provides the opportunity to examine the prevalence and incidence rates for dementia, Alzheimer dementia (AD), aMCI, and naMCI by demographic characteristics. Dementia prevalence was 6.5% (4.9% AD). Overall dementia incidence was 2.9/100 person-years (2.3/100 person-years for AD). Dementia and AD rates increased with age but did not differ by sex. Prevalence of aMCI was 11.6%, and naMCI prevalence was 9.9%. aMCI incidence was 3.8 and naMCI incidence was 3.9/100 person-years. Rates of aMCI increased significantly with age in men and in blacks; sex, education, and race were not significant risk factors. In contrast, naMCI incidence did not increase with age; however, blacks were at higher risk compared with whites, even when controlling for sex and education. Results highlight the public health significance of preclinical cognitive disease.