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Iris Asllani¹, Ajna Borogovac, Truman R. Brown, Arjun Kumar, Yaakov Stern

¹Columbia University, New York, New York, USA

CBF depression is considered an important correlate of normal aging which could at least partially explain the functional impairment in several processes in elderly. We compared CASL CBF images from young subjects with those from healthy elderly both at voxel- and ROI-wise level. As compared to the young group, the elderly subjects showed a signifiant decrease of ~ 24% in gray matter CBF, in good agreement with data from quantitative PET studies. Furthermore, the areas of CBF depression were consistent with their functional role in normal aging.

Fawzi Boumezbeur¹, Graeme F. Mason¹, Robin A. de Graaf¹, Gary W. Cline², Kevin L. Behar¹, Gerald I. Shulman², ³, Douglas L. Rothman¹, Kitt Falk Petersen²

¹Magnetic Resonance Research Center, Yale University, New Haven, USA; ²Yale School of Medicine, New Haven, USA; ³Howard Hughes Medical Institute, Yale School of Medicine, New Haven, USA

Age-related alterations in energy metabolism have been implicated as a key factor in many neurodegenerative diseases. In this study, ¹³C MR spectroscopy was combined with infusions of [1-¹³C]glucose and [2-¹³C]acetate to characterize quantitatively neuronal and astrocytic TCA cycle (V_TCAn,V_TCAa) as well as the glutamate-glutamine cycle (V_NT) rates in healthy elderly and young volunteers. Major metabolic changes were measured: 30% increase of V_TCAa (p=0.002), a 28% decrease of V_TCAn (p=0.013) and a 24% decrease of V_NT (p=0.03). Our results demonstrate that alterations in oxidative energy production in neurons and glia form a major characteristic of aging even in healthy elderly subjects.

Fawzi Boumezbeur¹, Robin A. de Graaf¹, Graeme F. Mason¹, Gary W. Cline², Kevin L. Behar¹, Gerald I. Shulman², ³, Douglas L. Rothman¹, Kitt Falk Petersen²

¹Magnetic Resonance Research Center, Yale University, New Haven, USA; ²Yale School of Medicine, New Haven, USA; ³Howard Hughes Medical Institute, Yale School of Medicine, New Haven, USA

For the past few years, many metabolite abnormalities in neurodegenerative diseases have been reported. In this study, we used short TE ¹H MR to measure significant age-related changes in NAA (-12%), Glu (-13%) and Ins (+28%) in healthy old people. Further, we correlated the metabolite concentrations with energy synthesis and neurotransmission fluxes (V_TCAa, V_TCAn and V_NT) measured in the same subjects using ¹³C MRS. Altogether, the results suggest a major evolution of the neuronal-astrocytic metabolic unit with normal aging and support the use of combined ¹H and ¹³C MRS to study the role of brain metabolism in the etiology of neurodegenerative diseases

Elisabetta Pagani¹, Federica Agosta¹, Domenico Caputo², Massimo Filippi¹, ³

¹Scientific Institute and University Ospedale San Raffaele, Milan, Italy; ²Scientific Institute Fondazione Don Gnocchi, Milan, Milan, Italy; ³Scientific Institute Fondazione Don Gnocchi, Milan, Italy

In this study, a method to measure WM fiber bundles atrophy using diffusion tensor MRI was used. The age-related changes of the WM volumes from 84 healthy subjects, spanning seven decade of life, were obtained at a voxel-based resolution. A linear correlation was found between age and WM decline in superior-frontal and parietal fibers, anterior cingulum bundles, fornix, and cerebellar peduncles. By contrast, a quadratic regression model best fitted age-related WM loss in the genu of corpus callosum, pons bundles, and inferio-fronto-occipital/uncinate fasciculi. These findings provide evidence that aging of the WM takes different courses and there is considerable variation from region to region in how the effects of age are expressed.

Zhihao Li¹, Anna Bacon Moore², ³, Callie Tyner², Xiaoping Hu¹

¹Emory Univ./Georgia Tech., Atlanta, Georgia, USA; ²Atlanta VAMC, Atlanta, Georgia, USA; ³Emory Univ., Atlanta, Georgia, USA

In the working memory associated brain network, reduction of structural connectivity is non-uniform with advancing age. This may be part of the neurobiological basis of the HAROLD (Hemispheric Asymmetry Reduction in Older Adults) effect.

Peter Andrew Hardy¹, David Kennedy Powell¹, Zhiming Zhang¹

¹University of Kentucky, Lexington, USA

Diffusion Tensor Imaging and Fractional Anisotropy analysis was used to correlate changes with age and with motor function in a cohort of healthy rhesus monkeys.

Ramtilak Gattu¹, Randall R. Benson², ³, Balaji Myrtheunjayan¹, Kristen Kennedy², Naftaki Raz², Zhifeng Kou⁴, Ewart M. Haacke⁵

¹Wayne State University, Detroit, USA; ²Wayne State University School of Medicine, Detroit, USA; ³Detroit Medical Center, Detroit, USA; ⁴Wayne State University School of Medicine, Detroit, Michigan, USA; ⁵wayne state university, Detroit, USA

Few DTI studies demonstrated the age effect on fractional anisotropy (FA). We examined the effect of age on FA for whole brain white matter and in corpus callosum (CC). 70 healthy volunteers (aged 19-81, SD= 19.22 years) were imaged with DTI on a 1.5T scanner. All three regions of CC (genu, body, and Splenium) showed a slight decline in FA with age, with the greatest age effect in genu.  This equates to a drop of .006 per decade. We also found a trend towards greater variance in FA with age suggesting a heterogeneous adverse effect of ageing on WM fibers.

Naoko Saito¹, Hernan Jara¹, Osamu Sakai¹

¹Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA

Purpose: To evaluate the regional T1 changes over the human lifespan with quantitative MR imaging (Q-MRI). Methods: 75 subjects (0.5-87 years) obtained with the mixed-TSE pulse sequence were segmented into six segments: bilateral frontal, bilateral posterior and bilateral cerebellar segments leading to six T1 histograms per subject. Results: For all ages studied, T1 of frontal GM was consistently and bilaterally longer than T1 of posterior GM, by about 10%. Conclusion: T1 relaxation mechanisms in frontal GM are weaker than in posterior GM over the full human lifespan suggesting different frontal vs. posterior tissue micro-architecture and/or hydration level.

Kieren Grant Hollingsworth¹, Julia L. Newton¹, Benjamin S. Aribisala¹, Peter Edward Thelwall¹, Roy Taylor¹, Andrew M. Blamire¹, David E. Jones¹

¹Newcastle University, Newcastle Upon Tyne, UK

Primary Biliary Cirrhosis is an autoimmune liver disease resulting in debilitating fatigue for 50% of affected patients. One hypothesis postulates that the fatigue may originate from metal deposition in the globus pallidus (GP), measurable in the magnetization transfer ratio (MTR), but normal ageing effects have not been taken into account to date. This study investigated an age-matched group of 30 early-stage patients and 14 volunteers, assessing GP MTR, T1 and T2. The same age-related trend was found in patients and controls and GP T2 correlated with measures of autonomic dysfunction.

Stefan Ropele¹, Christian Enzinger¹, Gernot Reishofer¹, Reinhold Schmidt¹, Franz Fazekas¹

¹Medical University Graz, Graz, Austria

The study goal was to explore if specific cerebrovascular risk factors may have an impact on the cerebral tissue matrix as assessed by the magnetization transfer ratio (MTR). Measurement of the MTR was done in white matter hyperintensities and in normal appearing brain tissue (NABT) of 328 neurologically asymptomatic elderly subjects. A multivariate regression model was used to study the effect of a large battery of possible risk factors on global and lesional MTR changes. Our results suggest that MTR changes in NABT are related predominantly to the ageing process per se. Diabetes and hypertension may exert some additional minor effects.