Background-Frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) is a heritable form of FTD, but the gene(s) responsible for the majority of autosomal dominant FTD-ALS cases have yet to be found. Previous studies have identified a region on chromosome 9p that is associated with FTD and ALS.

Figure copy is the most common method of visual spatial assessment in dementia evaluations, but performance on this test may be multifactorial. We examined the neuroanatomical substrates of figure copy performance in 46 patients with Alzheimer's disease (AD) and 48 patients with the behavioral variant of Frontotemporal dementia (bvFTD). A group of 94 neurologically healthy controls were studied for comparison. In AD, poor figure copy correlated significantly with right parietal cortex volumes but not with right dorsolateral prefrontal cortex volumes, whereas in bvFTD, figure copy performance correlated significantly with right dorsolateral prefrontal cortex volumes and there was only a trend with right parietal cortex volumes. The cognitive processes associated with figure copy performance also differed by diagnostic group such that figure copy was associated with spatial perception and attention in AD and with spatial planning and working memory in bvFTD. Spatial planning accounted for unique variance in the figure copy performance of bvFTD even after accounting for spatial perception, attention, and working memory. These results suggest that figure copy performance in AD and bvFTD is not anatomically-specific and is differentially impacted by bottom-up and top-down aspects of visual spatial processing. Alternative methods of visual spatial assessment for dementia evaluations are proposed. KeywordsVisuospatial; Parietal; Prefrontal; Dementia; Neurodegenerative; Neuropsychological Assessment; Visuoconstruction Visual spatial impairments are often among the first symptoms of neurodegenerative disease. Patients in the early stages of Alzheimer's disease (AD) often get lost, forget where they placed their belongings, and have trouble driving or parking their car (deIpolyi, Rankin, Mucke, Miller, & Gorno-Tempini, 2007;Hamilton, Fay, & Rockwood, 2009;Monacelli, Cushman, Kavcic, & Duffy, 2003;Pai & Jacobs, 2004). AD can impact a wide range of visual processes including contrast sensitivity, angle discrimination, motion perception, object recognition, mental rotation, and navigation learning, consistent with the impact of the disease on critical visual spatial processing areas in the parietal and temporal lobes (Rabinovici et al., 2007). Similarly, patients with the behavioral variant of frontotemporal Katherine L. Possin, Ph.D., University of California, San Francisco, 350 Parnassus Ste. 905, San Francisco, CA 94143-1207, kpossin@memory.ucsf.edu, tel: 415/476-1889 415/476-4800. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuropsyc...

Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI), at influencing cognitive processing speed among normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55–87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.