Benzodiazepine use and brain amyloid load in nondemented older individuals: a florbetapir PET study in the Multidomain Alzheimer Preventive Trial cohort

Abstract The primary dementia-protective benefits of Angiotensin receptor type 1 (AT1R) blockers (ARBs) are believed to arise from systemic effects on blood pressure. However, there is a brain-specific renin-angiotensin system (b-RAS) that acts mainly through three receptor subtypes: AT1R, AT2R, and AT4R. AT1R promotes inflammation and oxidative stress (OS). AT2R increases nitric oxide. AT4R is essential for dopamine release and mediates memory consolidation. Here, we aimed to investigate the effects of ARBs on b-RAS, OS, inflammation, PHF-tau, and beta-amyloid load. Postmortem frontal-cortex brains of age- and sex-matched cognitively intact (CI) individuals using (n=30) and not using ARBs (n=30) and Alzheimer's disease (AD) patients using (n=30) and not using ARBs (n=30) were studied. Protein levels of receptors were measured by Western blot. Protein carbonyl (PC) and cytokine levels were measured by ELISA. Tangle and amyloid-β scores were used as outcomes. In CI individuals, our data shows that ARB treatment was associated with higher protein levels of AT4R (median(range) 0.69(1.92) vs 0.17(1.18) CI+ARBs vs CI, p=0.02), lower level of OS marker PC (10.60(8.32) vs 11.26(7.44), CI+ARBs vs CI, p=0.03) and lower hippocampal and overall amyloid scores (0(5.45) vs 1.15(4.21) p=0.03, 0.79(12.75) vs 3.41(13.36) p=0.04, CI+ARBs vs CI, respectively). In AD group, ARB treatment was associated with lower AT1R protein levels (0.47(1.15) vs 0.59(1.99), AD+ARBs vs AD, p=0.02). No significant changes were observed in OS, inflammation, or PHF-tau and amyloid load in AD brains treated with ARBs. Our results highlight the impact of ARBs on the brains of cognitively intact and AD older individuals.

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Benzodiazepine use and neuroimaging markers of Alzheimer’s disease in nondemented older individuals: an MRI and 18F Florbetapir PET study in the MEMENTO cohort

Neuropsychopharmacology ◽

10.1038/s41386-021-01246-5 ◽

2021 ◽

Author(s):

Quentin Gallet ◽

Vincent Bouteloup ◽

Maxime Locatelli ◽

Marie-Odile Habert ◽

Marie Chupin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Older Individuals ◽

Benzodiazepine Use

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Education as a Moderator of the Relationship Between Episodic Memory and Amyloid Load in Normal Aging

The Journals of Gerontology Series A ◽

10.1093/gerona/glz235 ◽

2019 ◽

Vol 75 (10) ◽

pp. 1820-1826

Author(s):

Maude Joannette ◽

Christian Bocti ◽

Pénélope Sévigny Dupont ◽

Marie Maxime Lavallée ◽

Jim Nikelski ◽

...

Keyword(s):

Episodic Memory ◽

Cognitive Reserve ◽

Structural Mri ◽

University Education ◽

Older Individuals ◽

Cognitively Normal ◽

Amyloid Load ◽

University Degree ◽

The Relationship ◽

Linear Regressions

Abstract The current study explored whether education, a proxy of cognitive reserve, modifies the association between episodic memory (EM) performance and βeta-amyloid load (Aβ), a biomarker of Alzheimer’s disease, in a cohort of cognitively normal older adults. One hundred and four participants (mean age 73.3 years) evenly spread out in three bands of education were recruited. Participants underwent neuropsychological assessment, structural MRI as well as PET imaging to quantify Aβ load. Moderation analyses and the Johnson–Neyman technique were carried out to examine the interaction of education with Aβ load to predict EM performance. Linear regressions were then performed within each group of education to better illustrate the interaction effect (all analyses were controlled for age and sex). The interaction between education and Aβ load was significant (p < .05) for years of education, reaching a cutoff point of 13.5 years, above which the relationship between Aβ load and EM was no longer significant. Similarly, significant associations were found between Aβ and EM among participants with secondary (p < .01) and pre-university education (p < .01), but not with a university degree (p = .253). EM performance is associated with Aβ load in cognitively normal older individuals, and this relationship is moderated by educational attainment.

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Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load

Neurology ◽

10.1212/wnl.0000000000003585 ◽

2017 ◽

Vol 88 (6) ◽

pp. 569-576 ◽

Cited By ~ 19

Author(s):

Michel J. Grothe ◽

Sylvia Villeneuve ◽

Martin Dyrba ◽

David Bartrés-Faz ◽

Miranka Wirth ◽

...

Keyword(s):

Sex Education ◽

Gray Matter ◽

Gray Matter Volume ◽

Older Individuals ◽

Multimodal Neuroimaging ◽

Matter Volume ◽

Amyloid Pathology ◽

Aged Brain ◽

Age Related ◽

Amyloid Load

Objective:To comprehensively assess neurobiological effects of the protective APOE2 allele in the aged brain using a cross-sectional multimodal neuroimaging approach.Methods:Multimodal neuroimaging data were obtained from a total of 572 older individuals without dementia (cognitively normal and mild cognitive impairment) enrolled in the Alzheimer's Disease Neuroimaging Initiative and included assessments of regional amyloid load with AV45-PET, glucose metabolism with fluorodeoxyglucose-PET, and gray matter volume with structural MRI. Imaging indexes of APOE2 carriers were contrasted to risk-neutral APOE3 homozygotes, and analyses were controlled for age, sex, education, and clinical diagnosis. Additional models examined genotype-specific effects of age on the imaging markers.Results:In region-of-interest–based analyses, APOE2 carriers had significantly less precuneal amyloid pathology and did not show the typical age-related increase in amyloid load, although the age × genotype interaction was only trend-level significant. In contrast, parietal metabolism and hippocampal volume did not differ between APOE2 and APOE3 genotypes, and both groups showed comparable negative effects of age on these markers. The amyloid specificity of APOE2-related brain changes was corroborated in 2 complementary analyses: spatially unbiased voxel-wise analyses showing widespread reductions in amyloid deposition but no differences in gray matter volume or metabolism and an analysis of CSF-based biomarkers showing a significant effect on amyloid but not on tau pathology.Conclusions:Regarding the range of Alzheimer disease biomarkers considered in the present study, the APOE2 allele appears to have a relatively selective effect on reduced accumulation of amyloid pathology in the aged brain.

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Perceived Voice Disorders in Older Adults and Impact on Social Interactions

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2020_persp-20-00059 ◽

2021 ◽

pp. 1-8

Author(s):

Connie K. Porcaro ◽

Clare Singer ◽

Boris Djokic ◽

Ali A. Danesh ◽

Ruth Tappen ◽

...

Keyword(s):

Older Adults ◽

Social Interactions ◽

Social Engagement ◽

Leisure Activities ◽

Treatment Strategies ◽

Voice Disorders ◽

Community Dwelling ◽

Vocal Performance ◽

Older Individuals ◽

Cross Sectional

Purpose Many aging individuals, even those who are healthy, report voice changes that can impact their ability to communicate as they once did. While this is commonly reported, most do not seek evaluation or management for this issue. The purpose of this study was to investigate the prevalence and differences in voice disorders in older adults, along with the effect of fatigue on their social interactions. Method This is a cross-sectional investigation of a community-dwelling sample of individuals aged 60 years or older. Participants completed the Questionnaire on Vocal Performance, the Social Engagement Index subset “Engagement in Social or Leisure Activities,” and the Fatigue Severity Scale. Results Results indicated 32.5% of the 332 participants reported symptoms of voice problems with no difference found between male and female respondents. A slight increase in report of voice problems was noted with each year of age. Participants who self-reported voice problems indicated less interaction in social activities involving communication than those who did not. Finally, as severity of self-reported voice problems increased, an increase was reported by the same individuals for signs of fatigue. Conclusions Voice problems and resulting decreased social interaction are commonly experienced by older individuals. Voice symptoms in older adults have been found to benefit from evidence-based treatment strategies. It is critical to provide education to encourage older individuals to seek appropriate evaluation and management for voice issues through a speech-language pathologist or medical professional.

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Dual Task, Noise, and The Speech-Language Pathologist: A Clinical Guideline for Adult Multi-Tasking Intervention With Noise

Perspectives of the ASHA Special Interest Groups ◽

10.1044/persp2.sig15.32 ◽

2017 ◽

Vol 2 (15) ◽

pp. 32-41

Author(s):

Jennine Harvey ◽

Scott Seeman ◽

Deborah von Hapsburg

Keyword(s):

Dual Task ◽

Clinical Guideline ◽

Older Individuals ◽

Speech Language Pathology ◽

Speech Language Pathologist ◽

Hearing In Noise ◽

Hearing Function ◽

Language Pathology ◽

Relationship Of ◽

The Relationship

The field of Cognitive Hearing Science examines the relationship between cognitive, linguistic, and hearing functions. Although these areas are of particular importance to speech-language pathology, few studies have investigated applications of cognitive hearing science to clinical practice. The purpose of this review article is to (1) explore and present a summary of cognitive hearing science techniques for dual-task and hearing-in-noise procedures and implications to speech-language pathology, and (2) provide a clinical guide for speech-language pathology in adult multitasking intervention with noise. It is well understood that areas of cognitive skill and hearing function decline with age; therefore, additional understanding of the relationship of these functions is of particular importance to speech-language pathologists working with older individuals. This article meets the American Speech-Language-Hearing Association's (ASHA's) Special Interest Group (SIG) 15's mission of “research-to-practice” professional development by “promoting understanding of the effects of normal and pathological aging on cognition, language […] and hearing” (ASHA, 2017), and is intended to be of interest to the SIG 15 readership.

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