Interactions Between Brain 18F-FDG PET Metabolism and Hemodynamic Parameters at Different Ages of Life: Results From a Prospective Cross-Sectional Study.

Brain 18F-FDG PET imaging is useful to characterize accelerated brain aging at a pre-symptomatic stage. This study aims to examine the interactions between brain glycolytic metabolism and hemodynamic parameters in different age groups. Methods: A total of 72 patients (from 23 to 88 years of age, 38 women) without any cerebral diseases but with available cardiac, arterial peripheral, and central blood pressure measurements as well as arterial stiffness parameters obtained from brachial pressure and applanation tonometry and a brain 18F-FDG PET scan were prospectively included into this study. Quantitative voxel-to-voxel analyses were carried out to test for negative associations between brain glycolytic metabolism and individual hemodynamic parameters (p-voxel of <0.001 for the whole population and <0.005 for age groups). Results: The heart rate parameter of the whole population showed the most extensive associations with brain metabolism (15,857 mm3, T-score: 5.1), predominantly affecting the frontal and temporal regions (69% of the volume). Heart rate for the younger age group, systolic and pulse pressure for the 41-60-year-old group, and diastolic pressure for the older group were most extensively associated with brain metabolism and mainly involved the fronto-temporal lobes (respective involvement of 52.8%, 60.9%, and 65.5%) which are also the regions implicated in accelerated brain aging. Conclusion: This cross-sectional prospective study identified extensive associations between cerebral metabolism and hemodynamic parameters, indicating common aging mechanisms. Heart rate throughout adult life, systolic and pulse pressure parameters around middle age, and diastolic pressure parameters in older patients, suggest the existence of potentially therapeutic targets to prevent accelerated brain aging.

Age-associated evolution of plasmatic amyloid in mouse lemur primates: relationship with intracellular amyloid deposition.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Amyloid-ß peptide (Aß) deposition in the brain is one of its hallmarks, and the measure of plasma Aß is considered to be a biomarker for anti-amyloid drug efficacy in animal models of AD. However, age-associated plasmatic Aß modulation in animal models is practically never addressed in the literature. Mouse lemur primates are used as a model of normal and AD-like cerebral aging. Here, we studied the effect of age on plasmatic Aß in 58 mouse lemurs aged from 1 to 10 years. A subset of animals presented high plasmatic Aß, and the proportion of animals with high plasmatic Aß was higher in aged animals as compared with young ones. Histologic evaluation of the brain of some of these animals was carried out to assess extracellular and intracellular amyloid load. In aged lemurs, plasmatic Aß was negatively correlated with the density of neurons accumulating deposits of Aß.

Elevated Tau Level in Aged Rat Cerebrospinal Fluid Reduced by Treatment with a Neurotrophic Compound.

Alzheimer's disease (AD) is the single major cause of dementia in middle- to old-age individuals, and, as of yet, no disease-modifying therapeutic drug is available for its treatment. A major obstacle in the successful development of disease-modifying therapeutic drugs has been the lack of suitable animal models of the sporadic form of AD as well as a biomarker that can be used both for therapeutic preclinical studies and for human clinical trials. Previously we showed neurogenesis and neuronal plasticity deficits and cognitive impairment and their rescue with a neurotrophic peptidergic compound, DGGLAG named P021, in aged Fisher rats. Here we show that P021 is blood-brain-barrier-permeable, and chronic oral treatment with this compound can reduce the brain level of total tau in the aged rats. Furthermore, cerebrospinal fluid (CSF) levels of both tau and Aß/AßPP are elevated in the aged animals, and chronic treatment with P021 can reduce tau but not Aß/AßPP to that of the levels found in young adult rats. Importantly, P021 does not induce any detectable immune reaction in rats. Collectively, these studies show the therapeutic potential of P021 as a disease-modifying compound and the suitability of the aged Fisher rats as a model of cerebral aging in which the therapeutic efficacy of a tau-reducing compound can be monitored in the CSF.

Artistic creativity, artistic production, and aging.

This chapter reviews the changes produced by age on various aspects of artistic painting, particularly creativity and actual production. Aging in trained painters is often accompanied by a decline in creativity, which in turn is due to the cognitive decline related to aging. It has been argued, however, that aging does not cause a decline, but only changes in style and content. The two views are not mutually exclusive, and we present examples illustrating both aspects. We also show that, in addition to cognitive changes, impairment of sensory organs, especially vision, and of the bones and joints, may also produce marked changes in an artist's production and style. We conclude by showing that finding ways to induce creativity in persons who do not consider themselves artists can be a way of stimulating creativity and contribute to successful aging.

Chronic depression as a model disease for cerebral aging.

Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The "neurogenesis hypothesis of depression" posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression. Stress, neuroinflammation, dysfunctional insulin regulation, oxidative stress, and alterations in neurotrophic factors possibly contribute to the development of depression. The influence of antidepressant therapies, namely pharmacotherapy and neuroprotectants, on cellular plasticity are summarized. A dysfunction of complex neuronal networks as a consequence of neural degeneration in neuropsychiatric diseases has led to the application of deep brain stimulation. We discuss the way depression seen in the light of the neurogenesis hypothesis can be used as a model disease for cerebral aging. A common pathological mechanism in depression and cerebral aging-a dysfunction of neuroprotection and neurogenesis-is discussed. This has implications for new treatment methods.

Los conceptos neurobiológicos que están a la base de la depresión mayor han cambiado su enfoque desde las disfunciones en la neurotransmisión a disfunciones en la neurogénesis y en la neuroprotección. La "hipótesis de la neurogénesis de la depresión" postula que los cambios en la tasa de neurogénesis constituyen el mecanismo que subyace a la patología y al tratamiento de la depresión mayor. Es posible que el estrés, la neuroinflamación, la disfunción de la regulación de insulina, el estrés oxidatívo y las alieraciones en los factores neurotróficos contribuyan al desarrollo de la depresión. Se resume la influencia de las terapias antidepresivas en la plasticidad neuronal, como son la farmacoterapia y los neuroprotectores. La estimulación cerebral profunda se ha aplicado a partir de disfunciones de redes neuronales complejas, producto de la degeneración neuronal en enfermedades neuropsiquiátricas. Se discute la manera en que la depresión desde la perspectiva de la hipótesis de la neurogénesis pueda ser empleada como modelo de enfermedad del envejecimiento cerebral. Se discute un mecanismo patológico común en la depresión y el envejecimiento cerebral -una disfunción de la neuroprotección y de la neurogénesis- lo que tiene efectos para nuevos métodos terapéuticos.

Les concepts neurobiologiques sous-tendant la dépression majeure sont passés des dysfonctions de la neurotransmission aux dysfonctions de la neurogenèse et de la neuroprotection. « L'hypothèse neurogénésique de la dépression ¼ postule que le mécanisme qui sous-tend la pathologie et le traitement d'une dépression majeure est celui de modifications du taux de neurogenèse. Le stress, la neuro-inflammation, un dysfonctionnement de la régulation en insuline, le stress oxydatif et des modifications des facteurs neurotrophiques peuvent participer au développement de la dépression. L'article résume l'Influence des traitements antidépresseurs, c'est-à-dire des traitements pharmacologiques et des neuroprotecteurs sur la plasticité cellulaire. La stimulation cérébrale profonde est née de l'observation d'une dysfonction des réseaux neuronaux complexes suite à une neurodégénérescence lors des maladies neuropsychiatriques. Nous analysons la possibilité d'utiliser la dépression envisagée sous la lumière de l'hypothèse neurogénésique comme modèle pathologique du vieillissement cérébral. Nous étudions un mécanisme commun à la dépression et au vieillissement cérébral, une dysfonction de la neuroprotection et de la neurogenèse, ce qui a des conséquences en termes de nouvelles méthodes thérapeutiques.

Computed tomographic features of the feline brain change with advancing age?

Abstract: A better understanding of normal or expected encephalic changes with increasing age in cats is needed as a growing number of these animals is attended in veterinary clinics, and imaging data referring to normal age-associated changes are extremely scarce in the literature. The objective of this study was to identify age-related changes in feline brain using CT imaging. Fifteen non-brachycephalic healthy cats with age between 1 to 6 years (adult group) and others over 12 years (geriatric group) were submitted to CT scan of the brain. Statistically significant differences were found between the groups for the ability to identify the left lateral ventricle and for falx cerebri calcification, both identified in a greater number of cats of the geriatric group. A significantly higher mean width of the third ventricle was also detected in geriatric animals. There were no statistically significant differences between lateral ventricular dimensions and encephalic parenchymal attenuation on pre and post-contrast CT phases. The results of the present study show an increase in the incidence of falx cerebri calcification and a third ventricular dilatation with advancing age in cats. Future researches using MRI scanners and a greater quantity of cats are needed in order to identify supplementary age-related changes.

Resumo: Uma melhor compreensão das alterações encefálicas normais ou esperadas com o aumento da idade em gatos é necessária no presente momento, uma vez que tem havido um número crescente desses animais nas clínicas veterinárias, e dados de imagem referentes às alterações normais associadas à idade são extremamente escassos na literatura. O objetivo deste estudo foi a identificação de alterações relacionadas à idade no encéfalo de gatos através da tomografia computadorizada. Quinze gatos saudáveis não braquicefálicos com idade entre 1 e 6 anos (grupo adulto) e mais de 12 anos (grupo geriátrico) foram submetidos à tomografia encefálica. Diferenças estatísticas significativas foram encontradas entre os grupos para a identificação do ventrículo lateral esquerdo e calcificação da foice cerebral, ambos visualizados em um número maior de gatos do grupo geriátrico. A média de largura do terceiro ventrículo também foi significativamente maior nos animais geriátricos. Não foram encontradas diferenças estatísticas significativas entre a mensuração dos ventrículos laterais e a atenuação do parênquima encefálico nas fases tomográficas pré e pós-contraste. Os resultados do presente estudo demonstram aumento da incidência de calcificação da foice cerebral e dilatação do terceiro ventrículo de acordo com o avanço da idade em gatos. Pesquisas futuras utilizando ressonância magnética e uma maior quantidade de gatos são necessárias a fim de se identificar alterações complementares relacionadas à idade.

Computed tomographic features of the feline brain change with advancing age? / O aspecto tomográfico do encéfalo de felinos altera com o avanço da idade?

A better understanding of normal or expected encephalic changes with increasing age in cats is needed as a growing number of these animals is attended in veterinary clinics, and imaging data referring to normal age-associated changes are extremely scarce in the literature. The objective of this study was to identify age-related changes in feline brain using CT imaging. Fifteen non-brachycephalic healthy cats with age between 1 to 6 years (adult group) and others over 12 years (geriatric group) were submitted to CT scan of the brain. Statistically significant differences were found between the groups for the ability to identify the left lateral ventricle and for falx cerebri calcification, both identified in a greater number of cats of the geriatric group. A significantly higher mean width of the third ventricle was also detected in geriatric animals. There were no statistically significant differences between lateral ventricular dimensions and encephalic parenchymal attenuation on pre and post-contrast CT phases. The results of the present study show an increase in the incidence of falx cerebri calcification and a third ventricular dilatation with advancing age in cats. Future researches using MRI scanners and a greater quantity of cats are needed in order to identify supplementary age-related changes.(AU)

Uma melhor compreensão das alterações encefálicas normais ou esperadas com o aumento da idade em gatos é necessária no presente momento, uma vez que tem havido um número crescente desses animais nas clínicas veterinárias, e dados de imagem referentes às alterações normais associadas à idade são extremamente escassos na literatura. O objetivo deste estudo foi a identificação de alterações relacionadas à idade no encéfalo de gatos através da tomografia computadorizada. Quinze gatos saudáveis não braquicefálicos com idade entre 1 e 6 anos (grupo adulto) e mais de 12 anos (grupo geriátrico) foram submetidos à tomografia encefálica. Diferenças estatísticas significativas foram encontradas entre os grupos para a identificação do ventrículo lateral esquerdo e calcificação da foice cerebral, ambos visualizados em um número maior de gatos do grupo geriátrico. A média de largura do terceiro ventrículo também foi significativamente maior nos animais geriátricos. Não foram encontradas diferenças estatísticas significativas entre a mensuração dos ventrículos laterais e a atenuação do parênquima encefálico nas fases tomográficas pré e pós-contraste. Os resultados do presente estudo demonstram aumento da incidência de calcificação da foice cerebral e dilatação do terceiro ventrículo de acordo com o avanço da idade em gatos. Pesquisas futuras utilizando ressonância magnética e uma maior quantidade de gatos são necessárias a fim de se identificar alterações complementares relacionadas à idade.(AU)