Showing papers by "Patrick R. Hof published in 2001"

Anterior cingulate cortex pathology in schizophrenia and bipolar disorder.

Abstract: To explore possible morphological abnormalities in the dorsal and subgenual parts of anterior cingulate cortex in mood disorders and schizophrenia, we performed a quantitative postmortem study of 44 schizophrenic patients, 21 patients with sporadic bipolar disorder, 20 patients with sporadic major depression, and 55 age- and sex-matched control cases. All individuals were drug naive or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Neuron densities and size were estimated on cresyl violet-stained sections using a stereological counting approach. The distribution and density of microtubule-associated (MAP2, MAP1b) and tau proteins were assessed by immunocytochemistry and quantitative immunodot assay. Mean total and laminar cortical thicknesses as well as mean pyramidal neuron size were significantly decreased in the dorsal and subgenual parts of areas 24 (24sg) in schizophrenic cases. Patients with bipolar disorder showed a substantial decrease in laminar thickness and neuron densities in layers III, V, and VI of the subgenual part of area 24, whereas patients with major depression were comparable to controls. Immunodot assay showed a significant decrease of both MAP2 and MAP1b proteins in bipolar patients but not in patients with schizophrenia and major depression. The neuroanatomical and functional significance of these findings are discussed in the light of current hypotheses regarding the role of areas 24 and 24sg in schizophrenia and bipolar disorder.

Functional neurobiology of aging

Abstract: Contributors. Foreword. Preface. Overview: Introduction to Concepts in Aging Research: Age-Specific Rates of Neurological Disease, J.E. Riggs. Nature versus Nurture in the Aging Brain, C.V. Mobbs and J.W. Rowe. Neurochemistry of Receptor Dynamics in the Aging Brain, B.J. Keck and J.M. Lakoski. Epidemiology of Neural Aging: Demography and Epidemiology of Age-Associated Neuronal Impairment, C.K. Cassel and K. Ek. Memory: Neocortical and Hippocampal Functions: Neuropsychology of Human Aging. Memory Changes with Aging and Dementia, P.D. Harvey and R.C. Mohs. Histology of Age-Related Cortical Changes in Humans: Types of Age-Related Brain Lesions and Relationship to Neuropathological Diagnostic Systems of Alzheimer's Disease, P. Giannakopoulos, E. Kovari, G. Gold, P.R. Hof, and C. Bouras. Morphological changes in Human Cerebral Cortex during Normal Aging, T. Bussiere and P.R. Hof. Longevity and Brain Aging: The Paradigm of Centenarians, C. Bouras, P.G. Vallet, E. Kovari, J.-P. Michel, F.R. Herrmann, P.R. Hof, and P. Giannakopoulos . Alzheimer's Disease: Regional and Laminar Patterns of Selective Neuronal Vulnerability in Alzheimer's Disease, P.R. Hof. Patterns of Cortical Neurodegeneration in Alzheimer's Disease: Subgroups, Subtypes, and Implications for Staging Strategies, B.A. Vogt, L.J. Vogt, and P.R. Hof. Non-Alzheimer Age-Associated Dementing Disorders: Vascular Dementia, G. Gold, C. Bouras, J.-P. Michel, P.R. Hof, and P. Giannakopoulos. Frontotemporal Dementias: From Classification Problems to Pathogenetic Uncertainties, P. Giannakopoulos, E. Kovari, G. Gold, P.R. Hof and C. Bouras. Progressive Supranuclear Palsy and Corticobasal Degeneration, D.W. Dickson. Neurobiology of Disorders with Lewy Bodies, L. Hansen and E. Masliah. Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex of Guam, D.P. Perl. In Vivo Imaging of Aging Brain: Brain Energy Metabolism: Cellular Aspects and Relevance to Functional Brain Imaging, P.J. Magistretti, S. Joray, and L. Pellerin. Functional Imaging in Cognitively Intact Aged People, N.D. Anderson and C.L. Grady. Functional Brain Studies of the Neurometabolic Bases of Cognitive and Behavioral Changes in Alzheimer's Disease, P. Pietrini, M.L. Furey, M. Guazzelli, and G.E. Alexander. Biochemical Correlates of Memory Impairments: Cholinergic Basal Forebrain Systems in the Primate Central Nervous System: Anatomy, Connectivity, Neurochemistry, Aging, Dementia, and Experimental Therapeutics, E.J. Mufson and J.H. Kordower. Glutamate Receptors in Aging and Alzheimer's Disease, A. Mishizen, M. Ikonomovic, and D.M. Armstrong. Tau Phosphorylation, L. Buee and A. Delacourte. Hereditary Basis of Alzheimer's Disease and Related Dementias: Etiology, Genetics, and Pathogenesis of Alzheimer's Disease, C. McKeon-O'Malley and R. Tanzi. Nonhereditary Mechanisms of Alzheimer's Disease: Inflammation, Free Radicals, Glycation, Metabolism and Apoptosis, and Heavy Metals, M.P. Mattson. Rodent Models of Age-Related Memory Impairments: Rodent Models of Age-Related Memory Impairments, D.K. Ingram. Genetically Engineered Models of Human Age-Related Neurogenerative Diseases, J.C. Vickers. Nonhuman Primate and Other Vertebrate Models of Brain Aging: Cognitive Aging in Nonhuman Primates, M.G. Baxter. Brain Aging in Strepsirhine Primates, E.P. Gilissen, M. Dhenain, and J.M. Allman. Age-Related Morphologic Alterations in the Brain of Old World and New World Anthropoid Monkeys, P.R. Hof and H. Duan. The Study of Brain Aging in Great Apes, J.M. Erwin, E.A. Nimchinsky, P.J. Gannon, D.P. Perl, and P.R. Hof. Neurobiological Models of Aging in the Dog and Other Vertebrate Species, E. Head, N.W. Milgram, and C.W. Cotman. Interventions: Estrogens and Alzheimer's Disease, N.D. Tsopelas and D.B. Marin. Cholinergic Treatments of Alzheimer's Disease, N.D. Tsopelas and D.B. Marin. Anti-Inflammatory and Antioxidant Therapies in Alzheimer's Disease, P.S. Aisen and G.M. Pasinetti. Senses: Sensory Cortices and Primary Afferent Functions: Vision: The Retina in Aging and in Alzheimer's Disease, R.O. Kuljis. Pathogenesis of Glaucomatous Optic Neuropathy, M.R. Hernandez and A.H. Neufeld. Color Vision, Object Recognition, and Spatial Localization in Aging and Alzheimer's Disease, A. Cronin-Golomb. Hearing: Anatomical and Neurochemical Bases of Presbycusis, R.D. Frisina, Jr. Age, Noise, and Ototoxic Agents, R.J. Salvi, D. Ding, A.C. Eddins, S.L. McFadden, and D. Henderson. Auditory Temporal Processing during Aging, D.R. Frisinia, R.D. Frisinia, Jr., K.B. Snell, R. Burkard, J.P. Walton, and J.R. Ison. Neurophysiological Manifestations of Aging in the Peripheral and Central Auditory Nervous System, J.P. Walton and R. Burkard. Genetics and Age-Related Hearing Loss, S.L. McFadden. Animal Models of Presbycusis and the Aging Auditory System, J.F. Willott. The Development of Animal Models for the Study of Presbycusis: Building a Behavioral Link between Perception and Physiology, J.R. Ison. Rehabilitation for Presbycusis, D.G. Sims and R. Burkard. Chemical Senses: Olfaction and Gustation in Normal Aging and Alzheimer's Disease, R.L. Doty. Locomotion: Basal Ganglia and Muscular Functions: Functional Impairments in Humans: Aging Effects on Muscle Properties and Human Performance, S.A. Jubrias and K.E. Conley. Parkinson's Disease: Symptoms and Age Dependency, S.A. Eshuis and K.L. Leenders. Pathology and Biochemistry of Aging and Disease of Basal Ganglia: The Basal Ganglia Dopaminergic Systems in Normal Aging and Parkinson's Disease, J.N. Joyce. Huntington's Disease, S.E. Browne and M.F. Beal. Animal Models: Biochemical and Anatomical Changes in Basal Ganglia of Aging Animals, J.A. Stanford, M.A. Hebert, and G.A. Gerhardt. Homeostasis: Hypothalamus and Related Systems: Reproduction and the Aging Brain: Male Sexual Behavior during Aging, H. Kuno, M. Godschalk, and T. Mulligan. Sexual Behavior in Aging Women, N.E. Avis. Factors Influencing the Onset of Female Reproductive Senescence, P.S. LaPolt and J.K.H. Lu. Female Sexuality during Aging, N.L. McCoy. Hypothalamic Neuropeptide Gene Expression in Postmenopausal Women, N.E. Rance and T.W. Abel. Neuroendocrine Aspects of Female Reproductive Aging, P.M. Wise and M.J. Smith. Hypothalamic Changes Relevant to Reproduction in Aging Male Rodents, D.A. Gruenewald and A.M. Matsumoto. Metabolism and the Aging Brain: Regulation of Energy Intake in Old Age, S.B. Roberts and N.P. Hays. Thermoregulation during Aging, B.A. Horwitz, A.M. Gabaldon, and R.B. McDonald. Biological Rhythms and the Aging Brain: Sleep and Hormonal Rhythms in Humans, G. Copinschi, R. Leproult, and E. Van Cauter. Circadian Rhythms and Sleep in Aging Rodents, D.E. Kolker and F.W. Turek. Glucocorticoid Secretion and the Aging Brain: Clucocorticoids and the Aging Brain: Cause or Consequence? P.J. Lucassen and E.R. De Kloet. Growth Hormone, Insulin-like Growth Factor-1, and the Aging Brain, P.L. Thornton and W.E. Sonntag. Automatic Nervous System and the Aging Brain: The Aged Sympathetic Nervous System, G.A. Kuchel and T. Cowen. Appendix. Basic Genetic Concepts.

Cytology of human caudomedial cingulate, retrosplenial, and caudal parahippocampal cortices.

Abstract: Brodmann showed areas 26, 29, 30, 23, and 31 on the human posterior cingulate gyrus without marking sulcal areas. Histologic studies of retrosplenial areas 29 and 30 identify them on the ventral bank of the cingulate gyrus (CGv), whereas standardized atlases show area 30 on the surface of the caudomedial region. This study evaluates all areas on the CGv and caudomedial region with rigorous cytologic criteria in coronal and oblique sections Nissl stained or immunoreacted for neuron-specific nuclear binding protein and nonphosphorylated neurofilament proteins (NFP-ir). Ectosplenial area 26 has a granular layer with few large pyramidal neurons below. Lateral area 29 (29l) has a dense granular layer II-IV and undifferentiated layers V and VI. Medial area 29 (29m) has a layer III of medium and NFP-ir pyramids and a layer IV with some large, NFP-ir pyramidal neurons that distinguish it from areas 29l, 30, and 27. Although area 29m is primarily on the CGv, a terminal branch can extend onto the caudomedial lobule. Area 30 is dysgranular with a variable thickness layer IV that is interrupted by large NFP-ir neurons in layers IIIc and Va. Although area 30 does not appear on the surface of the caudomedial lobule, a terminal branch can form less that 1% of this gyrus. Area 23a is isocortex with a clear layer IV and large, NFP-ir neurons in layers IIIc and Va. Area 23b is similar to area 23a but with a thicker layer IV, more large neurons in layer Va, and a higher density of NFP-ir neurons in layer III. The caudomedial gyral surface is composed of areas 23a and 23b and a caudal extension of area 31. Although posterior area 27 and the parasubiculum are similar to rostral levels, posterior area 369 differs from rostral area 36. Subregional flat maps show that retrosplenial cortex is on the CGv, most of the surface of caudomedial cortex is areas 23a, 23b, and 31, and the retrosplenial/parahippocampal border is at the ventral edge of the splenium. Thus, Brodmann’s map understates the rostral extent of retrosplenial cortex, overstates its caudoventral extent, and abridges the caudomedial extent of area 23. J. Comp. Neurol. 438:353‐376, 2001. © 2001 Wiley-Liss, Inc.

Anatomical distribution of serotonin-containing neurons and axons in the central nervous system of the cat.

Abstract: By using a monoclonal antibody to serotonin (5-HT), an immunohistochemical study was undertaken to provide a comprehensive description of the 5-HT-containing neurons and of the distribution of their axonal processes in the cat brain and spinal cord. The localization of cell bodies was comparable to that previously reported in studies using formaldehyde-induced fluorescence and other 5-HT antibodies, with a large proportion of labeled neurons in the raphe nuclei and a minor, yet not negligible number, in the ventral, lateral, and dorsal reticular formation. The ascending efferent non-varicose axons were best visualized in sagittal sections and mainly seen taking a rostroventral direction through the tegmentum. The varicose axons could be grossly classified into thin and large fibers, according to the size and shape of the immunoreactive varicosities, which were elongated (up to 2 mm in length and 1 mm in width) or round (2‐ 4 mm in diameter). Varicose axonal arborizations invaded almost every region of the gray matter and avoided large myelinated bundles except in the spinal cord. Variations in the density of the plexuses of immunoreactive fibers generally followed the anatomical divisions and were also observed within nuclei, especially in laminated structures. Only the superior olivary complex could be regarded as devoid of 5-HTcontaining axons. A few areas contained extremely rich fiber plexuses. These were the olfactory tubercle, nucleus accumbens, ventral mesencephalon, periventricular gray from the hypothalamus to the pons, facial nucleus, subdivisions of the inferior olive, and the intermediolateral nucleus in the spinal cord. Varicose axons formed tight pericellular arrays in the neocortex, mainly the ectosylvian gyrus, and in the lateral septum and medullar magnocellular nucleus. These data, combined with those of the literature concerning the synaptic versus non-synaptic mode of termination of the 5-HT-immunoreactive varicosities and the high number of distinct receptors, are indicative of the multiple possible actions of serotonin in the central nervous system. J. Comp. Neurol. 433:157‐182, 2001. © 2001 Wiley-Liss, Inc. Indexing terms: 5-hydroxytryptamine; efferent bundles of axons; immunohistochemistry; raphe nuclei; varicose axons

Clinical validity of A beta-protein deposition staging in brain aging and Alzheimer disease.

Abstract: Braak's neurofibrillary tangle (NFT) pathology staging system of Alzheimer disease (AD) correlates generally with clinical data. Recently, Braak's group proposed an Abeta-protein staging based on the progression of amyloid deposition in the medial temporal lobe. To examine its clinical validity and evaluate whether it adds predictive power to NFT-based staging, we performed a study comparing both neuropathological classifications with clinical dementia rating scale (CDR) scores in a large autopsy series. The 2 neuropathological staging systems were strongly correlated. Their association with clinical severity was highly significant. However, the strength of the relationship was greater for NFT-based staging. It accounted for 26.5% of the variability in clinical severity, Abeta-protein-based staging for 13.0%, and age for 4.4%. Compared to NFT-based staging, the Abeta-protein-based system was less able to distinguish mild cognitive changes from dementia and showed marked overlap among the various stages of cognitive decline. In a multivariate model, NFT and age together accounted for 27.2% of the clinical variability and the addition of Abeta-protein deposition staging could only explain an extra 2.9%. Our data support the close relationship between NFT progression and amyloid formation within the medial temporal lobe proposed by Braak's group but demonstrate the limited value of Abeta-protein deposition staging in terms of clinicopathological correlations.

Age-Related Morphologic Alterations in the Brain of Old World and New World Anthropoid Monkeys

Abstract: Anthropoid monkeys are subdivided into two large groups, the New World platyrrhine monkeys (callithricids and cebids) and the Old World catarrhine monkeys (macaques, baboons, guenons, and leaf-eating monkeys). Most taxa are poorly known from a neurobiological point of view, but many species are used for laboratory studies (in particular, some macaques and baboons [Macaca and Papio], the Patas monkey [Erythrocebus], and the Central and South American marmoset [Callthrix], owl [Aotus], squirrel [Saimiri], and capuchin [Cebus] monkeys). Aging is particularly well documented among these taxa from the long-tailed and rhesus macaques and from the squirrel monkey. The neurobiological basis of declining cortical function in primate aging remains to be defined. One possibility is that the structural integrity of the neocortex is compromised by frank neuronal degeneration, synaptic loss, or other morphologic alterations. The consensus emerging from recent studies, however, is that many cortical areas, including subdivisions of the hippocampal, prefrontal, motor, and sensory cortices known to participate critically in sensory integration and memory-related processes, are relatively resistant to cell death during normal aging in monkeys. In contrast, subcortical structures are more consistently affected in a manner that correlates with the severity of cognitive deficits. Importantly, recent ultrastructural and cellular analyses have demonstrated that subtle alterations involving the neuropil as well as restricted domains of the dendritic trees are likely to contribute massively, together with molecular changes in specific neurotransmitter receptor proteins, to the cognitive and memory deficits observed in aged anthropoid monkeys.

The Study of Brain Aging in Great Apes

Abstract: The great apes are the closest biological relatives of humans. The resemblence is close from genetics to brain structure and cognitive function. Endocasts from fossil hominoids and hominids reveal that the brains of Australopithecus were similar in size and shape to those of modern chimpanzees, and that a dramatic increase in brain size occurred as Homo evolved. Studies of extant great apes (bonobos, chimpanzees, gorillas, and orangutans) in the wild and in captivity have provided evidence on patterns of sociality, behavior, communication, cognition, and self–awareness. These data have identified many characteristics that are apparently homologous among apes and humans, suggesting that these were also present in a common ancestor. Cerebral lateral asymmetries recently reported in the great apes suggest that some of the neurological foundations of language have long been present in the ape-human lineage. Neuronal loss with aging is associated with neurodegenerative pathology in humans. Studies of great ape brains using quantitative stereology have not yet found substantial neuronal loss associated with aging in the entorhinal cortex and CA1 field of the hippocampus, regions that are especially vulnerable to age-related cell loss in humans. However, two neuronal types have been recently found in anterior cingulate cortex that are unique to humans and great apes. One of these cell types, a large spindle cell found in a region implicated in self-awareness and regulation of autonomic functions, is diminished by about 60% in human victims of Alzheimer's disease. The application to great apes of improved methods of assessing cognitive decline, genetic risk, and gene expression, along with functional imaging and quantitative stereological research, offers prospects of additional insights into normal and pathological brain aging.

Patterns of Cortical Neurodegeneration in Alzheimer's Disease: Subgroups, Subtypes, and Implications for Staging Strategies

Abstract: Normal brain aging into the ninth decade is associated with cognitive impairments that are quantitative in nature rather than forming subgroups of changes and it is not associated with appreciable neuron degeneration. In contrast, although age is a risk factor for Alzheimer's disease (AD), cognitive deficits form statistically unique subgroups and the patterns of neocortical neurodegeneration occur according to early deficits. There is substantial evidence for clincopathological subgroups and some studies suggest the possibility of subtypes. A subtype is comprised of cases with unique clinical deficits, pattern of brain lesions, and etiology. One possible AD subtype are patients with early spastic paraparesis associated with the deletion of exon 9 from the presenilin 1 gene, a unique type of senile plaque, and degeneration of the corticospinal tract. Also suggestive of subtypes are different laminar patterns of neurodegeneration in posterior cingulate cortex. These patterns of neuron death are not compatible with a linear regression model of large neuron death, but rather a multivariate model based on principal components analysis. Because AD is not composed of a single pattern of clinical, cognitive, and pathological lesions, staging at postmortem examination can only be used as a general guide to the level of neurofibrillary and amyloid deposition in the cerebral cortex. The presence of clinicopathological subgroups, the lack of a strong relationship between neuron death and neurofibrillary tangles, and the possibility of subtypes raise the specter that no current staging strategy precisely defines disease status. Thus, linear regression of population variables and simple staging need to be replaced by multivariate models and assessments of disease progression that accommodate many statistical and topographical subgroups and/or subtypes of AD.

Morphological Changes in Human Cerebral Cortex during Normal Aging

Abstract: Alzheimer's disease (AD) is the most frequent cause of dementia in industrialized countries and has become one of the most studied age-related neuropsychiatric illnesses. However, the clinical assessment of AD in its early stages is still awaiting accurate and reliable tools that can be used to assess the progression of the disease and to evaluate emerging therapeutics interventions, although numerous studies have shown that results obtained from the neuropathological examination of AD brains are usually well correlated with clinical data. The major histopathologic hallmarks of AD are extracellular amyloid deposits referred to as senile plaques (SP), intraneuronal fibrillar inclusions referred to as neurofibrillary tangles (NFT), and neuronal and synaptic loss. The decline of cognitive functions observed in AD patients is reflected by the regional distribution and density of these lesions and by synapse loss and neuron death, which results in the disruption of major cortical circuits. However, SP and NFT are also present in brains from cognitively and intellectually preserved elderly individuals. A consistent neurofibrillary pathology restricted to the entorhinal cortex and the hippocampus occurs consistently in the brain of unaffected individuals and in patients with very mild cognitive impairment. Conversely, the distribution pattern of SP is variable among these individuals. Investigation of the regional and laminar localization of AD-related lesions simultaneously in nondemented subjects and patients with very mild cognitive impairment is important to understand the difference between normal aging and dementing process and to elucidate the pathogenetic mechanisms leading to the onset of the disease.

Types of Age-Related Brain Lesions and Relationship to Neuropathologic Diagnostic Systems of Alzheimer's Disease

Abstract: Neurofibrillary tangles, senile plaques, and neuronal loss are the three major pathologic hallmarks of Alzheimer's disease (AD); however, they are also observed in the course of normal brain aging. In recent years, the classical neuropathological description of these changes has been tentatively replaced by an integrative view, including morphological, biochemical, and molecular characteristics. The first part of this chapter focuses on the description of AD-related lesions and attempts to highlight possible relationships between their structure and hypotheses regarding their etiopathogenesis. Moreover, the time evolution and codependence of these lesions in the aged brain is discussed. The second part of this chapter provides a critical review of diagnostic systems for the neuropathological diagnosis of AD. Comparative analysis of these systems is presented with particular reference to their theoretical framework, validity, and acceptance.

11 – Vascular Dementia

Abstract: Atherosclerotic dementia was described in the late 19th century by Binswanger (1894) and Alzheimer (1895) at a time when syphilis was a leading cause of dementia and mental illness. For most of the 20th century, senile dementia was thought to result from decreased cerebral perfusion due to vascular disease. However, in the mid-1970s, Alzheimer's disease (AD) became recognized as the main cause of dementia, and interest in dementia of vascular origin waned. Since then, the concept has broadened and newer criteria have been proposed that have taken advantage of evolving neuroimaging techniques. At the dawn of the 21st century, vascular dementia (VaD) remains an important cause of dementia and a diagnostic challenge (Bowler and Hachinski, 1996; Desmond, 1996; Gold et al., 1999; Chiu et al., 2000). Although preventive strategies are likely to be highly beneficial, effective therapeutic interventions have yet to developed (Hachinski, 1992).

Quantification of the total neuronal structure of the fear conditioning circuit of the lateral amygdala of the rat

Abstract: During Pavlovian auditory fear conditioning a previously neutral auditory stimulus (CS) gains emotional significance through pairing with a noxious unconditioned stimulus (US). These associations are believed to be formed by way of plasticity at auditory input synapses on principal neurons in the lateral nucleus of the amygdala (LA). In order to begin to understand how fear memories are stored and processed by synaptic changes in the LA, we have quantified both the entire neural number and the sub-cellular structure of LA principal neurons.We first used stereological cell counting methods on Gimsa or GABA immunostained rat brain. We identified 60,322+/-1408 neurons in the LA unilaterally (n=7). Of these 16,917+/-471 were GABA positive. The intercalated nuclei were excluded from the counts and thus GABA cells are believed to represent GABAergic interneurons. The sub-nuclei of the LA were also independently counted. We then quantified the morphometric properties of in vitro electrophysiologically identified principal neurons of the LA, corrected for shrinkage in xyz planes. The total dendritic length was 9.97+/-2.57mm, with 21+/-4 nodes (n=6). Dendritic spine density was 0.19+/-0.03 spines/um (n=6). Intra-LA axon collaterals had a bouton density of 0.1+/-0.02 boutons/um (n=5). These data begin to reveal the finite cellular and sub-cellular processing capacity of the lateral amygdala, and should facilitate efforts to understand mechanisms of plasticity in LA.

Frontotemporal Dementias: From Classification Problems to Pathogenetic Uncertainties

Abstract: The term frontotemporal dementia has been used to classify several clinical syndromes previously described based on a relatively homogeneous symptomatology Patients in this diagnostic group present with an insidious and gradual change in personality and social conduct, early deficits of mental manipulation, sequencing and hierarchical organization processes, frontal-type amnesia, contrasting with preserved orientation, visuoconstructive and visuospatial abilities Frontotemporal dementia may represent more than 20% of degenerative dementias and is currently considered as the third most common cause of dementia after Alzheimer's disease and Lewy body dementia Biochemical and molecular genetic studies have made it possible to identify at least three biologically homogeneous subgroups of frontotemporal dementias: typical frontotemporal dementia cases with no tau or ubiquitin-positive neuronal and glial inclusions, two tauopathies, namely Pick's disease and frontotemporal dementia with parkinsonism linked to chromosome 17, and one ubiquitin-related disorder, the frontotemporal dementia with motor neuron disease We provide here a detailed overview of current concepts regarding the clinical characteristics and etiopathogenesis of these conditions

Longevity and Brain Aging: The Paradigm of Centenarians

Abstract: The exponential increase in the prevalence of Alzheimer's disease with age, as well as the consistent presence of Alzheimer's disease pathologic changes in elderly people, has induced much debate regarding the relationships between brain aging and Alzheimer's disease. In this context, the study of nonagenarians and centenarians is of particular interest because it allows one to define the spectrum and extent of changes in brain morphology that occur near the upper age limit of life and to assess whether Alzheimer's disease is on a continuum with normal brain aging. The epidemiological and neuropathological evidence summarized in this chapter supports that Alzheimer's disease is an age-related pathologic condition, which does not represent an inevitable consequence of ageing. Moreover, it suggests the presence of a particular subgroup of oldest-old individuals with high resistance to the neurodegenerative process. These observations are discussed within the theoretical framework of human longevity.