Clinical validity of Braak neuropathological staging in the oldest-old
ABSTRACT Several studies have demonstrated a good correlation between clinical severity and Braak's neuropathological staging in Alzheimer's disease (AD). However, nonagenarians and centenarians display a different pattern of cortical vulnerability to the neurodegenerative process compared to younger elderly, and it is not known whether correlations between clinical severity and neuropathological stages remain valid in this age group. To address this issue we compared Clinical Dementia Rating scale (CDR) scores and Braak stages in 116 patients over 90 years of age with either no cognitive impairment or very mild to severe AD. There is a strong positive correlation between CDR scores and Braak staging (Spearman coefficient = 0.66; P < 0.01). However, neuropathological staging does not distinguish cases with normal cognition (CDR 0) from those with mild cognitive changes (CDR 0.5). Unlike younger cohorts, Braak stages I and II are frequently associated with questionable dementia in this age group. Braak stage III overlaps with all CDR levels and correlates poorly with cognitive function. Braak stages IV or greater are consistently associated with at least mild dementia. Consistent with our previous neuropathological analyses of nonagenarians and centenarians, the present data suggest that the substantial involvement of the hippocampus which characterizes Braak stage IV is a key step in the development of overt clinical signs of dementia in the oldest-old. Moreover, they indicate that Braak staging represents a broad concept of the evolution of neurofibrillary tangles rather than a precise hierarchical model associated with a stepwise deterioration of cognitive abilities near the upper limit of life.
- SourceAvailable from: St J Baloyannis
[Show abstract] [Hide abstract]
- "After mounting in Permount, the sections were studied in a photomicroscope (Zeiss Axiolab). Neuropathological alterations were estimated and rated according to Braak and Braak staging   and CERAD neuritic plaque score  . The consensus recommendations concerning the neuropathological diagnosis of AD introduced by the National Institute on Aging and the Reagan Institute  were also respected. "
ABSTRACT: Alzheimer's disease (AD) is a progressive degeneration of the brain, inducing memory decline, inability in learning, and behavioral alterations, resulting progressively in a marked deterioration of all mental activities and eventually a vegetative state. The main causative factor, however, is still unclear. The implication of amyloid-β, AβPP, tau protein, the selective loss of neurons, the alteration of the synapses, the cytoskeletal changes, and the morphological alterations of the brain capillaries contribute substantially to the pathogenetic profile of the disease, without sufficiently enlightening the initial steps of the pathological procedures. The ultrastructure of the neuronal organelles as well as histochemical studies revealed substantial alterations, primarily concerning mitochondria. In this study, the morphological and morphometric alterations of the Golgi apparatus (GA) are described in the Purkinje cells of the cerebellum in twenty AD brains, studied with electron microscopy. As it is well established, GA has a very important role to play in many procedures such as glycosylation, sulfation, and proteolysis of protein systems, which are synthesized in the endoplasmic reticulum of nerve cells and glia. GA may also play a crucial role in protein trafficking and in misfolding of protein aggregates. In addition, the hyperphosphorylation of tau protein is closely related with the pathology of GA. In AD cases, described in this study, an obvious fragmentation of the cisternae of GA was observed in the Purkinje cells of the vermis and the cerebellar hemispheres. This alteration of GA may be associated with alterations of microtubules, impaired protein trafficking, and dendritic, spinal, and synaptic pathology, since protein trafficking plays an essential role in the three dimensional organization of the dendritic arbor and in the integrity of the synaptic components.Journal of Alzheimer's disease: JAD 06/2014; 42. DOI:10.3233/JAD-132660 · 4.15 Impact Factor
[Show abstract] [Hide abstract]
- "These results promote the notion of an overlap in AD neuropathological lesions in older subjects with or without dementia. Neuropathological studies have also shown that the association between clinical AD diagnosis and neuropathological features was more important in younger persons than in older subjects (Gold et al., 2000; Middleton et al., 2011; Savva et al., 2009). However, a possible limitation to our findings is the use of patients with non-AD cognitive disorders as controls instead of cognitively normal individuals. "
ABSTRACT: Increasing age is the most important risk factor for developing Alzheimer's disease (AD). The aim of this study was to investigate the relationships between age and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ 1-42), total Tau and phosphorylated Tau (pTau-181), in AD and non-AD patients explored for cognitive disorders. 966 patients (AD, n=528; non-AD, n=438) were included between January 2008 and December 2010 (mean age, 69.5years; mean MMSE, 20.2) from three French memory centers. Multivariable linear regression models were used to study the relationship between CSF biomarker levels and age in AD and non-AD patients. The capacity of each CSF biomarker in discriminating patients was evaluated using the area under the receiver-operating characteristic (ROC) curves by quartile of distribution of age. In AD patients, older age was associated with higher CSF Aβ 1-42 and lower Tau levels. Conversely, in non-AD patients, age was associated with lower CSF Aβ 1-42, higher Tau, and higher pTau-181 levels. In sex-stratified analysis, these relationships were significant only in women. Using ROC curve analysis, CSF AD biomarkers were more discriminant in younger patients than in older ones. In this clinically-based study, younger patients with AD had exacerbated CSF anomalies compared to older patients with AD. CSF biomarkers were more discriminant in younger patients than in older ones for the diagnosis of AD, especially in women. These results support the idea of an overlap in AD neuropathological lesions in oldest subjects with or without AD.Neurobiology of Disease 02/2013; 54. DOI:10.1016/j.nbd.2013.01.023 · 5.20 Impact Factor
[Show abstract] [Hide abstract]
- "So far, from a neuropathological point of view, the progression of disease from MCI state to later stages seems to follow a linear course. Nevertheless, there is some evidence from functional    and biochemical studies  that the process of conversion from nondemented to clinically evident demented state is not so linear. Recent fMRI studies have suggested increased medial temporal lobe (MTL) activations in MCI subjects versus controls, during the performance of memory tasks  . "
ABSTRACT: We evaluated the relationship between brain rhythmicity and both the cerebrovascular damage (CVD) and amygdalohippocampal complex (AHC) atrophy, as revealed by scalp electroencephalography (EEG) in a cohort of subjects with mild cognitive impairment (MCI). All MCI subjects underwent EEG recording and magnetic resonance imaging. EEGs were recorded at rest. Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands. In the spectral band power the severity of CVD was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. On the other side, the group with moderate hippocampal atrophy showed the highest increase of alpha2 and alpha3 power. Moreover, when the amygdalar and hippocampal volumes are separately considered, within amygdalohippocampal complex (AHC), the increase of theta/gamma ratio is best associated with amygdalar atrophy whereas alpha3/alpha2 ratio is best associated with hippocampal atrophy. CVD and AHC damages are associated with specific EEG markers. So far, these EEG markers could have a prospective value in differential diagnosis between vascular and degenerative MCI.07/2012; 2012:917537. DOI:10.1155/2012/917537