Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease.

Sites of early neuropathologic change provide important clues regarding the initial clinical features of Alzheimer's disease (AD). We have shown significant reductions in hippocampal synaptic density in participants with AD, consistent with the early degeneration of entorhinal cortical (ERC) cells that project to hippocampus via the perforant path. In this study, [C]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A) and [F]flortaucipir binding to tau were measured via PET in 10 participants with AD (5 mild cognitive impairment, 5 mild dementia) and 10 cognitively normal participants.

Association of Aβ deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [C]UCB-J.

Background: Attempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET).

Cognitively Impaired Older Persons' and Caregivers' Perspectives on Dementia-Specific Advance Care Planning.

Background/objectives: Advance care planning (ACP) traditionally involves asking individuals about their treatment preferences during a brief period of incapacity near the end of life. Because dementia leads to prolonged incapacity, with many decisions arising before a terminal event, it has been suggested that dementia-specific ACP is necessary. We sought to elicit the perspectives of older adults with early cognitive impairment and their caregivers on traditional and dementia-specific ACP.

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Introduction: Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density.

Methods: We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [ C]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio.

PET imaging of mGluR5 in Alzheimer's disease.

Background: Metabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer's disease (AD) by mediating the synaptotoxic action of amyloid-β oligomers. We utilized the positron emission tomography (PET) radioligand [F]FPEB to investigate mGluR5 binding in early AD.

Methods: Sixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid.