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Aim: Understanding the relationship between age-related gait impairment, such as slow gait, and executive functioning in seniors may help identify individuals at higher risk of mobility decline, falls, and progression to dementia at earlier stages. We aim to identify brain regions concomitantly associated with poor gait and executive functioning in a cohort of well-functioning elderly women., Methods: In total, 149 well-functioning women aged 70.1 ± 6.2 years underwent FDG-PET to evaluate regional cerebral metabolic rates of glucose normalized in reference to cerebellar glucose metabolic value (normalized-rCMRglc) in 16 brain areas. We assessed gait speed, step length and cadence under usual and fast conditions. Executive function was assessed using Trail-Making-Tests (TMT) A and B., Results: Adjusted multiple regression analyses for potential covariates showed that TMT-B and ΔTMT (TMT B-A) were associated with gait speed and cadence at fast condition. Lower normalized-rCMRglc in the posterior cingulate and primary sensorimotor cortices were associated with longer TMT-B and ΔTMT times (i.e., lower executive function) as well as with slower gait speed and lower cadence at fast condition. Slower gait speed and lower cadence at fast condition were also associated with lower normalized-rCMRglc in the occipital and parietal cortices. There were no other significant associations., Conclusions: In healthy elderly women without impending disability or cognitive impairment, reduced glucose metabolism in the posterior cingulate and primary sensorimotor cortices were associated with both lower gait performance and executive functioning. Our results suggest that gait control and executive functions might share the same neural substrate. Geriatr Gerontol Int 2017; 17: 1873-1880., (© 2017 Japan Geriatrics Society.)

Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD., (© 2015 International Society of Neuropathology.)

Background: The objective of this study was to investigate the relationship between normalized regional cerebral metabolic rates of glucose (normalized-rCMRglc) and gait function in physically and mentally high-functioning older women., Methods: One hundred eighty-two community-dwelling older women (mean age [SD], 69.4 [6.6] years) without disability in instrumental activities of daily living and without mobility limitations underwent positron emission tomography with 18F-fluorodeoxyglucose at rest to assess brain activity associated with gait function. We measured normalized-rCMRglc in 16 regions of interest. Within 6 months of the positron emission tomography with 18F-fluorodeoxyglucose scan, gait speed, step length, and step frequency both at comfortable and maximum paces were measured as indices of gait function. Associations between normalized-rCMRglc and gait indices were examined with multiple linear regression analyses adjusted for demographic characteristics, including age, height, body weight, blood pressure, past illness, and education., Results: Slower maximum gait speed even in the range of individual difference was associated with lower normalized-rCMRglc in the prefrontal, posterior cingulate, and parietal cortices. Lower step frequency at the maximum pace was also associated with lower normalized-rCMRglc in these regions. However, there was no significant association between step length at the maximum pace and normalized-rCMRglc or between all gait variables at a comfortable pace and normalized-rCMRglc., Conclusions: The normalized-rCMRglc values in specific regions were associated with individual differences in gait function, even in healthy older women. These regions of the cerebrum could play an important role in gait control. Understanding the cerebral glucose metabolism in these brain regions may enable early detection of mobility limitation., (© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The positioning or selection of a region of interest (ROI) is an essential step for the quantification of brain images. However, so long as the ROIs were manually selected, results obtained fluctuated considerably with subtle changes in their positioning. To perform an ROI analysis of the brain with improved objectivity and excellent reproducibility, we recently established fully automated ROI-based analysis software for the brain, the so-called 3DSRT and the FineSRT. 3DSRT performed by consecutive analyzing process as follows: (1) anatomical standardization using the SPM99 algorithm; (2) analysis using constant 318 ROIs divided into 12 groups (segments) on each hemisphere; (3) calculation of the area-weighted average for each of the respective 24 segments; (4) display of the results followed by the saving of respective values of the 636 ROIs (both hemispheres). The processes of the FineSRT were fundamentally similar to that of 3DSRT, but on FineSRT more precise constant 1394 ROIs (both hemispheres) corresponding to the respective cerebral convolutions were used. Our programs have been useful for objective estimation of cerebrovascular reserve, especially for follow-up studies of an infant with moyamoya disease, because we could compare the results without consideration of the patient's growth during the follow-up period.

The aim of this study was to determine the areas involved in episodes of transient global amnesia (TGA) by calculation of cerebral blood flow (CBF) using 3DSRT, fully automated ROI analysis software which we recently developed. Technetium-99m L, L-ethyl cysteinate dimer single-photon emission tomography ((99m)Tc-ECD SPET) was performed during and after TGA attacks on eight patients (four men and four women; mean study interval, 34 days). The SPET images were anatomically standardized using SPM99 followed by quantification of 318 constant ROIs, grouped into 12 segments (callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus and cerebellum), in each hemisphere to calculate segmental CBF (sCBF) as the area-weighted mean value for each of the respective 12 segments based on the regional CBF in each ROI. Correlation of the intra- and post-episodic sCBF of each of the 12 segments of the eight patients was estimated by scatter-plot graphical analysis and Pearson's correlation test with Fisher's Z-transformation. For the control, (99m)Tc-ECD SPET was performed on eight subjects (three men and five women) and repeated within 1 month; the correlation between the first and second sCBF values of each of the 12 segments was evaluated in the same way as for patients with TGA. Excellent reproducibility between the two sCBF values was found in all 12 segments of the control subjects. However, a significant correlation between intra- and post-episodic sCBF was not shown in the thalamus or angular segments of TGA patients. The present study was preliminary, but at least suggested that thalamus and angular regions are closely involved in the symptoms of TGA.

Regional resting cerebral blood flow and vascular reserve in a patient with transient global amnesia (TGA) were evaluated during and after a TGA episode using 99mTc-ethyl cysteinate dimer (ECD). The patient had consecutive SPECT studies before and after acetazolamide (ACZ) administration with adjunctive radionuclide angiography using equal-volume-split 99mTc-ECD. SPECT study during TGA episode showed poor vasodilatory reactivity to ACZ in the left medial temporal region involving the hippocampus and resting hypoperfusion in the regions bilaterally. The resting hypoperfusion with reserved vasodilatory reactivity to ACZ also was seen in the bilateral thalami. Abnormal findings in these regions disappeared on the follow-up SPECT study 15 days after the onset. No previous SPECT evaluation of regional abnormalities of both hemodynamic reserve and resting perfusion during and after an episode of TGA has been reported.

To evaluate noninvasive regional cerebral blood flow (CBF) measurements using technetium-99m-L, L-ethyl cysteinate dimer (99mTc-ECD), radionuclide angiography, resting- and acetazolamide-activating-SPECT studies were performed during about one hour. Forty-four cases with diagnosis of cerebral ischemic disorders were studied. For 36 cases (Group "Acz"), radionuclide angiography was performed immediately after intravenous bolus injection of 300 MBq of 99mTc-ECD, followed by the consecutive SPECT studies. In the midst of the first SPECT study, acetazolamide was administered. Just after the completion of the first SPECT study, another 300 MBq of 99mTc-ECD was added and the second SPECT study was started. For the remaining 8 cases (Group "Placebo"), physiological saline was administered instead of acetazolamide. Quantitative flow-mapping image was calculated from the qualitative SPECT image by the application of Patlak plot graphical analysis and Lassen's correction. Group "Placebo" showed no increase of mean CBF (mCBF) between the resting- and the placebo-challenged-SPECT image (2nd mCBF/1st mCBF; 98 +/- 5%). Group "Acz" showed 124 +/- 15% increase of mCBF under acetazolamide activation. By use of these quantitative flow-mapping images, acetazolamide-activated CBF increase was recognized clearly and easily. This noninvasive method is easy to perform and may be helpful to measure cerebral perfusion changes in the acetazolamide test.

We report here that the specific Fab' fragment of anti-nerve growth factor (NGF)-antibody (anti-NGF, 12, 120 and 400 micrograms/4 weeks, i.c.v.) impairs learning and memory. The goal latency of the control rats in water maze task was rapidly shortened by training compared to those of the anti-NGF-treated rats. The degree of reduction in movement counts of the anti-NGF-treated rats in habituation task was significantly smaller than that of the control rats. However, the step-through latency of the anti-NGF-treated rats was not significantly shorter than that of the control rats. With regard to the choline acetyltransferase activity, no effects were observed in any of the brain regions. Anti-NGF treatment altered nuclear morphology in the hippocampus and parietal cortex. As a result, it seems that the anti-NGF-induced amnesia could be due to an impairment of nuclear morphology.