Alzheimer's & dementia : the journal of the Alzheimer's Association
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The mechanism triggering degeneration in Alzheimer's disease (AD) remains uncertain. Therapeutic failure following amyloid β (Aβ) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer's pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown. ⋯ People with DS and trisomy 21 produce a large amount of Aβ. If Alzheimer's pathology occurred in DS without microvascular loss or endothelial impairment, a direct neurotoxic Aβ mechanism would be supported and microvascular impairment rejected. The observation of microvascular impairment in DS with Alzheimer's disease changes fails to reject the microvascular hypothesis and provides some support for this potential mechanism of injury.
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Comparative Study
Bridging cognitive screening tests in neurologic disorders: A crosswalk between the short Montreal Cognitive Assessment and Mini-Mental State Examination.
To provide a crosswalk between the recently proposed short Montreal Cognitive Assessment (s-MoCA) and Mini-Mental State Examination (MMSE) within a clinical cohort. ⋯ The s-MoCA is quick to administer, provides high sensitivity and specificity for cognitive impairment, and now can be compared directly with the MMSE.
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For nearly 50 years, institutional review boards (IRB) and independent ethics committees have featured local oversight as a core function of research ethics reviews. However growing complexity in Alzheimer's clinical research suggests current approaches to research volunteer safety is hampering development of new therapeutics. As a partial response to this challenge, the NIH has mandated that all NIH-funded multi-site studies will use a single Institutional Review Board. The perspective describes a joint program to provide a single IRB of record (sIRB) for phases of multi-site studies. ⋯ The effort will initially accept protocols for studies of Alzheimer's disease, dementia, and related disorders effecting memory, movement and mood. Future aims will be to provide scientific review and, where applicable, regulatory and ethical review in an international context outside North America with sites possibly in Asia, Europe and Australia.
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Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD. ⋯ These early increases in Aβ1-42, P-T181-tau, and P-S396-tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.
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Benzodiazepine use has been associated with increased risk of dementia. However, it remains unclear whether the risk relates to short or long half-life benzodiazepines and whether it extends to other psychotropic drugs. ⋯ Results of this large, prospective study show increased risk of dementia for long half-life benzodiazepine and psychotropic use.