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Objectives To examine whether changes in the cardiac autonomic nervous system ( ANS) over time, as expressed by baroreflex sensitivity ( BRS), were associated with long-term changes in cognitive performance in elderly individuals without dementia. Design Community-based 8-year longitudinal study. Setting Clinical settings. Participants Individuals aged 66.9 ± 0.9 (N = 425). Measurements At baseline and follow-up, subjects underwent a clinical interview, autonomic and vascular measurements, and a neuropsychological evaluation including attentional, executive, and memory tests using standardized Z-scores. BRS was defined as being normal, moderate, or severe alteration at each evaluation. On the basis of the longitudinal changes subjects were stratified as being stable, moderate or improved. Results Mean attentional, executive, and memory change Z-scores were −0.41 ± 0.9, −0.15 ± 0.7, and −0.14 ± 0.8, respectively. BRS of 56% of the subjects remained unchanged, of 20% decreased, and of 24% improved. After regression analysis, the worsened BRS group was 1.88 times as likely to have greater memory change as the group with stable BRS ( P = .02). No significant association was found between longitudinal change in BRS and attentional and executive changes. Conclusion In healthy elderly individuals, BRS decrease was associated with a weak but significant decrease in memory function. The long-term effect of BRS on memory changes may suggest a role of the ANS in cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives To assess the role of the cardiac autonomic nervous system ( ANS), as measured according to spontaneous cardiac baroreflex sensitivity ( BRS), in the type and degree of cognitive performance in healthy young-elderly individuals, taking into account the presence of other vascular risk factors. Design Community-based cross-sectional study. Setting In-home and clinical settings. Participants A subset of participants, aged 66.9 ± 0.9, from a prospective study that aimed to assess the influence of ANS activity on cardiovascular and cerebrovascular morbidity and mortality (N = 916). Measurements All subjects underwent a clinical interview, neuropsychological testing, and autonomic and vascular measurements. Three cognitive domains were defined: attentional ( Trail- Making Test Part A, Stroop code and parts I & II), executive ( Trail- Making Test Part B, Stroop part III, verbal fluency and similarity tests), and memory (Benton visual retention test, Grober and Buschké procedure). Subjects were stratified according to their scores into normal, low, and impaired performers. Results After adjustments to demographic and vascular data, participants with moderate autonomic dysregulation (3 < BRS ≤ 6) were determined to be 1.82 times as likely to have memory impairment (odds ratio ( OR) = 1.82, 95% confidence interval ( CI) = 1.13-3.17, P = .02) and those with severe autonomic dysregulation ( BRS ≤ 3) to be 2.65 as likely ( OR = 2.65, 95% CI = 1.40-5.59, P = .006) as participants with normal BRS (>6). Conclusion In older individuals without dementia, autonomic dysregulation seems to have a direct, gradual, and independent effect on memory. Future studies are needed to evaluate the long-term effects of BRS and other markers of the ANS on cognitive decline. [ABSTRACT FROM AUTHOR]

TDP-43 (TAR-DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), as well as in frontotemporal lobar degeneration (FTLD) and FTLD associated with MND (FTLD-MND). Mutations in TARDBP gene, coding for TDP-43, were found in patients with pure MND. We now describe TARDBP mutations in two patients with FTLD-MND, presenting with a behavioral variant of FTLD and semantic dementia, suggesting that TDP-43 may also have a direct pathogenic role in FTLD disorders. Ann Neurol 2009;65:470-474 [ABSTRACT FROM AUTHOR]