Background-The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally (controls), those with a mild cognitive impairment (MCI), and those with probable AD.
Objectives-i) to assess the diagnostic specificity of MRI-defined hippocampal atrophy for Alzheimer's disease (AD) among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and, ii) to measure correlations among pre-mortem MRI measurements of hippocampal atrophy, mental status exam performance, and the pathologic stage of AD. Methods-An un-selected series of 67 individuals participating in the Mayo Alzheimer's DiseaseResearch Center/Alzheimer's Disease Patient Registry were identified who had undergone a standardized antemortem MRI study and also post-mortem examination. Hippocampal volumes were measured from antemortem MRI. Each post-mortem specimen was assigned a pathologic diagnosis, and in addition, the severity of AD pathology was staged using the method of Braak and Braak.Results-Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle-only degeneration usually had substantial hippocampal atrophy while those with changes of typical aging did not. Among all 67 subjects, correlations (all p<0.001) were observed between hippocampal volume and Braak stage (r = −0.39), between hippocampal volume and MMSE score (r = 0.60), and between MMSE score and Braak stage (r = −0.41).Conclusions-Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage [particularly among subjects with isolated AD pathology (r = −0.63, p = 0.001)] and consequent cognitive status.
Background: Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau proteins, are one
Background: Right temporal frontotemporal dementia (FTD) is an anatomic variant of FTD
Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods:In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results:The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions:Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease. Neurology ® 2011;77:866-874 GLOSSARY AD ϭ Alzheimer disease; BOLD ϭ blood oxygenation level-dependent; bvFTD ϭ behavioral variant frontotemporal dementia; DMN ϭ default mode network; FOV ϭ field of view; FTD ϭ frontotemporal dementia; FWE ϭ familywise error; ICA ϭ independent component analysis; MPRAGE ϭ magnetization-prepared rapid acquisition gradient echo; PPND ϭ pallido-ponto-nigral degeneration; ROI ϭ region of interest; TE ϭ echo time; TIV ϭ total intracranial volume; TR ϭ repetition time.Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder characterized by behavioral and language deficits.1,2 A large proportion of subjects with FTD have an autosomal dominant pattern of inheritance, 3,4 with many showing mutations in the microtubule associated protein tau (MAPT) gene.5 Subjects with mutations in MAPT typically present with behavioral variant FTD (bvFTD), with poor semantic abilities, 6 -8 and show predominant temporal atrophy, with less severe involvement of frontal and parietal lobes.9,10 Families characterized by the presence of mutations in MAPT provide the ideal construct to identify preclinical disease changes. Case studies assessing imaging in asymptomatic MAPT carriers show
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