Transcortical motor aphasia

The defining symptoms of transcortical motor aphasia (TCMA) are nonfluent verbal output with relatively preserved repetition. Other symptoms, such as naming difficulties, agrammatic output, or even some paraphasias, may occur, but these are not cardinal symptoms defining TCMA and are not necessary for the diagnosis. The core anatomy involved in TCMA is a lesion of the medial frontal cortex, especially the left presupplementary motor area (pre-SMA) and adjacent Brodmann’s area 32; a lesion of the left posterior inferior frontal cortex, especially pars opercularis and ventral lateral premotor cortex; or a lesion of the pathways between these frontal structures. TCMA occasionally has been reported with a lesion of the left basal ganglia, the left thalamus, or the ascending dopaminergic pathways. From a cognitive standpoint, TCMA can be conceptualized as a disorder of intention, in other words, as a disorder of initiation and continuation of spoken language that is internally motivated. The medial frontal cortex provides the impetus to speak; this impetus to speak is conveyed to lateral frontal structures through frontal-subcortical pathways where it activates various language production mechanisms. The influence of the ascending dopaminergic pathways may occur either through their heavy connections with the pre- SMA region or through their influence on the basal ganglia. The influence of the basal ganglia and thalamus probably occurs through their connections with the medial frontal cortex. Assessments for TCMA should involve a thorough evaluation of conversational or narrative language output and repetition. New treatments are available that attemto engage right- hemisphere intention mechanisms with left- hand movements and may be effective in TCMA. Although dopamine agonists have also shown some positive effects in increasing verbal output in TCMA, trials have been small, and some caution must be exercised in interpreting these findings

Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults

Elevated expression of β-amyloid (Aβ1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease

Frontal Metabolites and Alzheimer’s Disease Biomarkers in Healthy Older Women and Women Diagnosed with Mild Cognitive Impairment

Background: Women account for two thirds of the prevalence and incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Evidence suggest that sex may differently influence the expression of proteins amyloid-beta (Aβ1-42) and tau, for which early detection is crucial in prevention of the disease. Objective: We investigated the effect of aging and cerebrospinal fluid (CSF) levels of Aβ1-42 and tau on frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) in a cohort of cognitively normal older women and women with MCI. Methods: 3T single-voxel MRS was performed on the medial frontal cortex, using Point Resolved Spectroscopy (PRESS) and Mescher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) in 120 women (age range 50-85). CSF samples of Aβ1-42 and tau and scores of general cognition were also obtained. Results: Levels of frontal gamma aminobutyric acid (GABA+) were predicted by age, independently of disease and CSF biomarkers. Importantly, levels of GABA+ were reduced in MCI patients. Additionally, we found that levels of N-acetylaspartate relative to myo-inositol (tNAA/mI) predicted cognition in MCI patients only and were not related to CSF biomarkers. Conclusion: This study is the first to demonstrate a strong association between frontal GABA+ levels and neurological aging in a sample consisting exclusively of healthy older women with various levels of CSF tau and Aβ1-42 and women with MCI. Importantly, our results show no correlation between CSF biomarkers and MRS metabolites in this sample