P1‐206: Clinical features of Alzheimer disease with and without lewy bodies

Abstract

edu).Role of the Funder/Sponsor: The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.Supplemental content at jamaneurology.com Author Contributions: Dr Morris had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of Interest Disclosures:Dr Morris has participated or is currently participating in clinical trials of antidementia drugs sponsored by the following companies and studies: Janssen Immunotherapy, Pfizer, Eli Lilly/Avid Radiopharmaceuticals, the SNIFF (Study of Nasal Insulin to Fight Forgetfulness) study, and the A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease) trial. Dr Morris has served as a consultant for Lilly USA, ISIS Pharmaceuticals, and the Charles Dana Foundation. He receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by National Institutes of Health grants P50AG005681, P01AG003991, P01AG026276, and U19AG032438.Additional Information: The NACC database is funded by NIA/National Institutes of Health grant U01 AG016976. The NACC data were obtained from the NIA-funded AD centers (grants P30 AG019610 [PI Eric Reiman, MD] EXPOSURES-Standardized neuropathologic assessment and then brain autopsy after death. HHS Public Access MAIN OUTCOMES AND MEASURES-Clinical and neuropsychiatric test scores.RESULTS-The mean (SD) age at death was statistically significantly younger for participants who had AD with Lewy bodies (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2 [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More men than women had AD with Lewy bodies (P = .01). The frequency of having at least 1 APOE ε4 allele was higher for participants who had AD with Lewy bodies than for participants who had AD without Lewy bodies (P = .03). CONCLUSIONS AND RELEVANCE-Participants with both AD and Lewy body pathology have a clinical phenotype that may be distinguished from AD alone. The frequency of Lewy bodies in AD and the association of Lewy bodies with the APOE ε4 allele suggest potential common mechanisms for AD and Lewy body pathologies.The 2 neuropathological hallmarks of Alzheimer disease (AD) are the extracellular Aβ plaques and the intracellular neurofibrillary tangles, of which the latter is composed of hyperphosphorylated tau protein. 1 Lewy bodies are intraneuronal cytoplasmic inclusions comprising aggregates of α-synuclein 2,3 and are readily detected by immunohistochemistry using anti-α-synuclein antibodies. In up to 50% of cases of sporadic late-onset AD, comorbid Lewy bodies are found. 2 Lewy bodies are frequent in the setting of moderate-tosevere levels of A...

Relationships between lewy and tau pathologies in 375 consecutive non‐Alzheimer's olfactory bulbs

“…6 We found that LCIG improves motor fluctuations in spite of the target and results of DBS, but that best outcome is observed in patients who had previously undergone bilateral STN DBS, as confirmed by the only two studies describing the combination use of LCIG and DBS. 4,5 This finding is also in keeping with a previous study showing that patients on STN DBS are less prone to develop dyskinesias when challenged with high doses of L-dopa. 7 Two of our cases had unilateral DBS procedure attributed to surgical contraindications, when LCIG was not available in Canada.…”

“…3 Only two studies have described the combined use of LCIG and STN DBS. 4,5 We report on a series of PD cases treated with LCIG therapy while on DBS of different targets, particularly investigating whether their combined outcome was influenced by DBS results.…”

“…In contrast, it has been reported that subjects with Lewy bodies in the setting of advanced AD had both younger age at death and age of dementia onset compared with those without Lewy-related pathology. 5 In a hospitalbased cohort, Jellinger reported an association between concurrent Lewy-related pathology and Alzheimer's pathology, regardless of age at death in the 7th to 10th decades. 6 These findings suggest that disease-specific factors accelerate Lewy-related pathology in the olfactory bulb in AD.…”

Lewy body pathology in Alzheimer's disease: A clinicopathological prospective study

“…Indeed, mixed pathology is associated with faster cognitive decline in subjects with mild cognitive impairment or dementia, and shorter survival times [22][23][24] Thus, subjects with concurrent LB pathology in the treatment arm of a trial may reduce the chance of showing a clinically meaningful benefit. Furthermore, the relationship between LBs and amyloid is still unclear, and it is unknown whether LBs might confer resistance to anti-amyloid therapies.…”

Combined neuropathological pathways account for age‐related risk of dementia

“…15,16 Although Lewy bodies can contribute to dementia risk in the absence of AD neuropathology, Lewy bodies are common in persons with pathologically confirmed AD, 17,18 and individuals with both AD pathology and Lewy bodies show greater risk of cognitive decline or dementia. [19][20][21] Likewise, TAR DNA-binding protein 43 (TDP-43) aggregations are common in aging, in pathologically confirmed AD, and in combination with hippocampal sclerosis, 22,23 and TDP-43 aggregations increase the likelihood of dementia, including a clinical diagnosis of AD. 7,24 The extent to which these neuropathological pathways inter-relate and whether known neuropathologies can fully account for age-related increases in dementia risk is currently unknown.…”