Investigating the causality of metabolites involved in one-carbon metabolism with the risk and age at onset of Parkinson's disease: A two-sample mendelian randomization study
Neurobiol Aging. 2021 Jul 4:S0197-4580(21)00217-7. doi: 10.1016/j.neurobiolaging.2021.06.023. Online ahead of print.ABSTRACTWith the aging population and increasing life expectancy, Parkinson's disease (PD), a neurological disorder rapidly increasing in morbidity and mortality, is causing a huge burden on society and the economy. Several studies have suggested that one-carbon metabolites, including homocysteine, vitamin B6, vitamin B12 and folate acid, are associated with PD risk. However, the results remain inconsistent and controversial. Thus, we performed a two-sample Mendelian randomization (MR) study to detect the cau...
Source: Neurobiology of Aging - July 30, 2021 Category: Geriatrics Authors: Yating Zhao Dandan Tian Na Guo Chenguang Zhang Ruixia Zhu Xu Liu Jian Zhang Source Type: research

Age-related neuroinflammation and pathology in the locus coeruleus and hippocampus: beta-adrenergic antagonists exacerbate impairment of learning and memory in aged mice
This study examined effects of age and acute beta-blocker administration on LC and hippocampus pathology, neuroinflammation and learning and memory behavior in mice. Male mice, 3 and 18 months old, were administered propranolol (beta-blocker) or mabuterol (beta-adrenergic agonist) acutely around behavioral assessment. Terminal inflammatory markers in plasma, hippocampus and LC were assessed alongside histopathology. An increase in hippocampal and LC microgliosis and inflammatory proteins in the hippocampus was detected in aged mice. We report pathological hyperphosphorylation of the postsynaptic NMDA receptor subunit 2B (N...
Source: Neurobiology of Aging - July 28, 2021 Category: Geriatrics Authors: Andrew K Evans Heui Hye Park Nay Lui Saw Kratika Singhal Gaku Ogawa Ryan D Leib Mehrdad Shamloo Source Type: research

Associations of increased interstitial fluid with vascular and neurodegenerative abnormalities in a memory clinic sample
Neurobiol Aging. 2021 Jul 5;106:257-267. doi: 10.1016/j.neurobiolaging.2021.06.017. Online ahead of print.ABSTRACTThe vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF). We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be wi...
Source: Neurobiology of Aging - July 28, 2021 Category: Geriatrics Authors: Merel M van der Thiel Whitney M Freeze Inge C M Verheggen Sau May Wong Joost J A de Jong Alida A Postma Erik I Hoff Ed H B M Gronenschild Frans R Verhey Heidi I L Jacobs Inez H G B Ramakers Walter H Backes Jacobus F A Jansen Source Type: research

Age-related neuroinflammation and pathology in the locus coeruleus and hippocampus: beta-adrenergic antagonists exacerbate impairment of learning and memory in aged mice
This study examined effects of age and acute beta-blocker administration on LC and hippocampus pathology, neuroinflammation and learning and memory behavior in mice. Male mice, 3 and 18 months old, were administered propranolol (beta-blocker) or mabuterol (beta-adrenergic agonist) acutely around behavioral assessment. Terminal inflammatory markers in plasma, hippocampus and LC were assessed alongside histopathology. An increase in hippocampal and LC microgliosis and inflammatory proteins in the hippocampus was detected in aged mice. We report pathological hyperphosphorylation of the postsynaptic NMDA receptor subunit 2B (N...
Source: Neurobiology of Aging - July 28, 2021 Category: Geriatrics Authors: Andrew K Evans Heui Hye Park Nay Lui Saw Kratika Singhal Gaku Ogawa Ryan D Leib Mehrdad Shamloo Source Type: research

Associations of increased interstitial fluid with vascular and neurodegenerative abnormalities in a memory clinic sample
Neurobiol Aging. 2021 Jul 5;106:257-267. doi: 10.1016/j.neurobiolaging.2021.06.017. Online ahead of print.ABSTRACTThe vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF). We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be wi...
Source: Neurobiology of Aging - July 28, 2021 Category: Geriatrics Authors: Merel M van der Thiel Whitney M Freeze Inge C M Verheggen Sau May Wong Joost J A de Jong Alida A Postma Erik I Hoff Ed H B M Gronenschild Frans R Verhey Heidi I L Jacobs Inez H G B Ramakers Walter H Backes Jacobus F A Jansen Source Type: research

Effects of baseline serum uric acid and apolipoprotein E4 on longitudinal cognition and cerebral metabolism
Neurobiol Aging. 2021 May 24;106:223-231. doi: 10.1016/j.neurobiolaging.2021.05.003. Online ahead of print.ABSTRACTSerum uric acid, a natural antioxidant, may have a protective effect on the progression of Alzheimer's disease (AD). To investigate the effect of serum uric acid on longitudinal cognitive and brain metabolic changes, we utilized data on baseline serum uric acid levels, APOE genotyping, and longitudinal cognitive scores from the Alzheimer's Disease Neuroimaging Initiative for 1,343 participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia. In 979 participants, brain metabolism was me...
Source: Neurobiology of Aging - July 26, 2021 Category: Geriatrics Authors: Young-Gun Lee Mincheol Park Seong Ho Jeong Sung Woo Kang Kyoungwon Baik Jin Ho Jung Phil Hyu Lee Young Ho Sohn Byoung Seok Ye Alzheimer's Disease Neuroimaging Initiative Source Type: research

Positivity effect in aging: evidence for the primacy of positive responses to emotional ambiguity
Neurobiol Aging. 2021 Jun 22;106:232-240. doi: 10.1016/j.neurobiolaging.2021.06.015. Online ahead of print.ABSTRACTOlder compared to younger adults show greater amygdala activity to positive emotions, and are more likely to interpret emotionally ambiguous stimuli (e.g., surprised faces) as positive. While some evidence suggests this positivity effect results from a top-down, effortful mechanism, others suggest it may emerge as the default or initial response. The amygdala is a key node in rapid, bottom-up processing and patterns of amygdala activity over time (e.g., habituation) can shed light on the mechanisms underlying ...
Source: Neurobiology of Aging - July 26, 2021 Category: Geriatrics Authors: Nathan M Petro Ruby Basyouni Maital Neta Source Type: research

Effects of baseline serum uric acid and apolipoprotein E4 on longitudinal cognition and cerebral metabolism
Neurobiol Aging. 2021 May 24;106:223-231. doi: 10.1016/j.neurobiolaging.2021.05.003. Online ahead of print.ABSTRACTSerum uric acid, a natural antioxidant, may have a protective effect on the progression of Alzheimer's disease (AD). To investigate the effect of serum uric acid on longitudinal cognitive and brain metabolic changes, we utilized data on baseline serum uric acid levels, APOE genotyping, and longitudinal cognitive scores from the Alzheimer's Disease Neuroimaging Initiative for 1,343 participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia. In 979 participants, brain metabolism was me...
Source: Neurobiology of Aging - July 26, 2021 Category: Geriatrics Authors: Young-Gun Lee Mincheol Park Seong Ho Jeong Sung Woo Kang Kyoungwon Baik Jin Ho Jung Phil Hyu Lee Young Ho Sohn Byoung Seok Ye Alzheimer's Disease Neuroimaging Initiative Source Type: research

Positivity effect in aging: evidence for the primacy of positive responses to emotional ambiguity
Neurobiol Aging. 2021 Jun 22;106:232-240. doi: 10.1016/j.neurobiolaging.2021.06.015. Online ahead of print.ABSTRACTOlder compared to younger adults show greater amygdala activity to positive emotions, and are more likely to interpret emotionally ambiguous stimuli (e.g., surprised faces) as positive. While some evidence suggests this positivity effect results from a top-down, effortful mechanism, others suggest it may emerge as the default or initial response. The amygdala is a key node in rapid, bottom-up processing and patterns of amygdala activity over time (e.g., habituation) can shed light on the mechanisms underlying ...
Source: Neurobiology of Aging - July 26, 2021 Category: Geriatrics Authors: Nathan M Petro Ruby Basyouni Maital Neta Source Type: research

Variability in sub-threshold signaling linked to Alzheimer's disease emerges with age and amyloid plaque deposition in mouse ventral CA1 pyramidal neurons
Neurobiol Aging. 2021 Jun 26;106:207-222. doi: 10.1016/j.neurobiolaging.2021.06.018. Online ahead of print.ABSTRACTThe hippocampus is vulnerable to deterioration in Alzheimer's disease (AD). It is, however, a heterogeneous structure, which may contribute to the differential volumetric changes along its septotemporal axis during AD progression. Here, we investigated amyloid plaque deposition along the dorsoventral axis in two strains of transgenic AD (ADTg) mouse models. We also used patch-clamp physiology in these mice to probe for functional consequences of AD pathogenesis in ventral hippocampus, which we found bears sign...
Source: Neurobiology of Aging - July 24, 2021 Category: Geriatrics Authors: Matthew L Russo Elizabeth Molina-Campos Natividad Ybarra Annalise E Rogalsky Timothy F Musial Viviana Jimenez Loreece G Haddad Yuliya Voskobiynyk Gary X D'Souza Gabriel Carballo Krystina M Neuman Dane M Chetkovich M Matthew Oh John F Disterhoft Daniel A N Source Type: research

Variability in sub-threshold signaling linked to Alzheimer's disease emerges with age and amyloid plaque deposition in mouse ventral CA1 pyramidal neurons
Neurobiol Aging. 2021 Jun 26;106:207-222. doi: 10.1016/j.neurobiolaging.2021.06.018. Online ahead of print.ABSTRACTThe hippocampus is vulnerable to deterioration in Alzheimer's disease (AD). It is, however, a heterogeneous structure, which may contribute to the differential volumetric changes along its septotemporal axis during AD progression. Here, we investigated amyloid plaque deposition along the dorsoventral axis in two strains of transgenic AD (ADTg) mouse models. We also used patch-clamp physiology in these mice to probe for functional consequences of AD pathogenesis in ventral hippocampus, which we found bears sign...
Source: Neurobiology of Aging - July 24, 2021 Category: Geriatrics Authors: Matthew L Russo Elizabeth Molina-Campos Natividad Ybarra Annalise E Rogalsky Timothy F Musial Viviana Jimenez Loreece G Haddad Yuliya Voskobiynyk Gary X D'Souza Gabriel Carballo Krystina M Neuman Dane M Chetkovich M Matthew Oh John F Disterhoft Daniel A N Source Type: research

Variability in sub-threshold signaling linked to Alzheimer's disease emerges with age and amyloid plaque deposition in mouse ventral CA1 pyramidal neurons
Neurobiol Aging. 2021 Jun 26;106:207-222. doi: 10.1016/j.neurobiolaging.2021.06.018. Online ahead of print.ABSTRACTThe hippocampus is vulnerable to deterioration in Alzheimer's disease (AD). It is, however, a heterogeneous structure, which may contribute to the differential volumetric changes along its septotemporal axis during AD progression. Here, we investigated amyloid plaque deposition along the dorsoventral axis in two strains of transgenic AD (ADTg) mouse models. We also used patch-clamp physiology in these mice to probe for functional consequences of AD pathogenesis in ventral hippocampus, which we found bears sign...
Source: Neurobiology of Aging - July 24, 2021 Category: Geriatrics Authors: Matthew L Russo Elizabeth Molina-Campos Natividad Ybarra Annalise E Rogalsky Timothy F Musial Viviana Jimenez Loreece G Haddad Yuliya Voskobiynyk Gary X D'Souza Gabriel Carballo Krystina M Neuman Dane M Chetkovich M Matthew Oh John F Disterhoft Daniel A N Source Type: research

Resistance to developing brain pathology due to vascular risk factors: the role of educational attainment
We examined if education contributes to brain resistance by studying its influence on the association between vascular risk factors and brain pathology. In 4111 stroke-free and dementia-free community-dwelling participants (62.9 ± 10.7 years), we explored the association between vascular risk factors (hypertension and the Framingham Stroke Risk Profile [FRSP]) and imaging markers of brain pathology (markers of cerebral small vessel disease and brain volumetry), stratified by educational attainment level. Associations of hypertension and FSRP with markers of brain pathology were not significantly different between le...
Source: Neurobiology of Aging - July 23, 2021 Category: Geriatrics Authors: Joyce van Arendonk Pinar Yilmaz Rebecca Steketee Jend é L Zijlmans Sander Lamballais Wiro J Niessen Julia Neitzel M Arfan Ikram Meike W Vernooij Source Type: research

Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease
Neurobiol Aging. 2021 Jun 21;106:119-129. doi: 10.1016/j.neurobiolaging.2021.06.014. Online ahead of print.ABSTRACTAlthough beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with 18F-florbetapir may serve as biomarker for progression risk in Aβ-positive cognitively normal (CN) and MCI patients, including clinical follow-up data ...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Julia Pfeil Merle C Hoenig Elena Doering Thilo van Eimeren Alexander Drzezga G érard N Bischof Alzheimer's Disease Neuroimaging Initiative Source Type: research

Short-term dietary restriction maintains synaptic plasticity whereas short-term overfeeding alters cellular dynamics in the aged brain: evidence from the zebrafish model organism
Neurobiol Aging. 2021 Jun 19;106:169-182. doi: 10.1016/j.neurobiolaging.2021.06.010. Online ahead of print.ABSTRACTIncreased caloric intake (OF) impairs quality of life causing comorbidities with other diseases and cognitive deficits, whereas dietary restriction (DR) increases healthspan by preventing age-related deteriorations. To understand the effects of these opposing dietary regimens on the cellular and synaptic dynamics during brain aging, the zebrafish model, which shows gradual aging like mammals, was utilized. Global changes in cellular and synaptic markers with respect to age and a 12 week dietary regimen of OF a...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Elif Tugce Karoglu-Eravsar Melek Umay Tuz-Sasik Michelle M Adams Source Type: research

Healthy dietary intake moderates the effects of age on brain iron concentration and working memory performance
Neurobiol Aging. 2021 Jun 22;106:183-196. doi: 10.1016/j.neurobiolaging.2021.06.016. Online ahead of print.ABSTRACTAge-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, year...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Valentinos Zachariou Christopher E Bauer Elayna R Seago Georgia Panayiotou Edward D Hall D Allan Butterfield Brian T Gold Source Type: research

Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease
Neurobiol Aging. 2021 Jun 21;106:119-129. doi: 10.1016/j.neurobiolaging.2021.06.014. Online ahead of print.ABSTRACTAlthough beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with 18F-florbetapir may serve as biomarker for progression risk in Aβ-positive cognitively normal (CN) and MCI patients, including clinical follow-up data ...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Julia Pfeil Merle C Hoenig Elena Doering Thilo van Eimeren Alexander Drzezga G érard N Bischof Alzheimer's Disease Neuroimaging Initiative Source Type: research

Short-term dietary restriction maintains synaptic plasticity whereas short-term overfeeding alters cellular dynamics in the aged brain: evidence from the zebrafish model organism
Neurobiol Aging. 2021 Jun 19;106:169-182. doi: 10.1016/j.neurobiolaging.2021.06.010. Online ahead of print.ABSTRACTIncreased caloric intake (OF) impairs quality of life causing comorbidities with other diseases and cognitive deficits, whereas dietary restriction (DR) increases healthspan by preventing age-related deteriorations. To understand the effects of these opposing dietary regimens on the cellular and synaptic dynamics during brain aging, the zebrafish model, which shows gradual aging like mammals, was utilized. Global changes in cellular and synaptic markers with respect to age and a 12 week dietary regimen of OF a...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Elif Tugce Karoglu-Eravsar Melek Umay Tuz-Sasik Michelle M Adams Source Type: research

Healthy dietary intake moderates the effects of age on brain iron concentration and working memory performance
Neurobiol Aging. 2021 Jun 22;106:183-196. doi: 10.1016/j.neurobiolaging.2021.06.016. Online ahead of print.ABSTRACTAge-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, year...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Valentinos Zachariou Christopher E Bauer Elayna R Seago Georgia Panayiotou Edward D Hall D Allan Butterfield Brian T Gold Source Type: research

Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease
Neurobiol Aging. 2021 Jun 21;106:119-129. doi: 10.1016/j.neurobiolaging.2021.06.014. Online ahead of print.ABSTRACTAlthough beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with 18F-florbetapir may serve as biomarker for progression risk in Aβ-positive cognitively normal (CN) and MCI patients, including clinical follow-up data ...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Julia Pfeil Merle C Hoenig Elena Doering Thilo van Eimeren Alexander Drzezga G érard N Bischof Alzheimer's Disease Neuroimaging Initiative Source Type: research

Short-term dietary restriction maintains synaptic plasticity whereas short-term overfeeding alters cellular dynamics in the aged brain: evidence from the zebrafish model organism
Neurobiol Aging. 2021 Jun 19;106:169-182. doi: 10.1016/j.neurobiolaging.2021.06.010. Online ahead of print.ABSTRACTIncreased caloric intake (OF) impairs quality of life causing comorbidities with other diseases and cognitive deficits, whereas dietary restriction (DR) increases healthspan by preventing age-related deteriorations. To understand the effects of these opposing dietary regimens on the cellular and synaptic dynamics during brain aging, the zebrafish model, which shows gradual aging like mammals, was utilized. Global changes in cellular and synaptic markers with respect to age and a 12 week dietary regimen of OF a...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Elif Tugce Karoglu-Eravsar Melek Umay Tuz-Sasik Michelle M Adams Source Type: research

Healthy dietary intake moderates the effects of age on brain iron concentration and working memory performance
Neurobiol Aging. 2021 Jun 22;106:183-196. doi: 10.1016/j.neurobiolaging.2021.06.016. Online ahead of print.ABSTRACTAge-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, year...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Valentinos Zachariou Christopher E Bauer Elayna R Seago Georgia Panayiotou Edward D Hall D Allan Butterfield Brian T Gold Source Type: research

Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease
Neurobiol Aging. 2021 Jun 21;106:119-129. doi: 10.1016/j.neurobiolaging.2021.06.014. Online ahead of print.ABSTRACTAlthough beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with 18F-florbetapir may serve as biomarker for progression risk in Aβ-positive cognitively normal (CN) and MCI patients, including clinical follow-up data ...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Julia Pfeil Merle C Hoenig Elena Doering Thilo van Eimeren Alexander Drzezga G érard N Bischof Alzheimer's Disease Neuroimaging Initiative Source Type: research

Short-term dietary restriction maintains synaptic plasticity whereas short-term overfeeding alters cellular dynamics in the aged brain: evidence from the zebrafish model organism
Neurobiol Aging. 2021 Jun 19;106:169-182. doi: 10.1016/j.neurobiolaging.2021.06.010. Online ahead of print.ABSTRACTIncreased caloric intake (OF) impairs quality of life causing comorbidities with other diseases and cognitive deficits, whereas dietary restriction (DR) increases healthspan by preventing age-related deteriorations. To understand the effects of these opposing dietary regimens on the cellular and synaptic dynamics during brain aging, the zebrafish model, which shows gradual aging like mammals, was utilized. Global changes in cellular and synaptic markers with respect to age and a 12 week dietary regimen of OF a...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Elif Tugce Karoglu-Eravsar Melek Umay Tuz-Sasik Michelle M Adams Source Type: research

Healthy dietary intake moderates the effects of age on brain iron concentration and working memory performance
Neurobiol Aging. 2021 Jun 22;106:183-196. doi: 10.1016/j.neurobiolaging.2021.06.016. Online ahead of print.ABSTRACTAge-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, year...
Source: Neurobiology of Aging - July 20, 2021 Category: Geriatrics Authors: Valentinos Zachariou Christopher E Bauer Elayna R Seago Georgia Panayiotou Edward D Hall D Allan Butterfield Brian T Gold Source Type: research

Mutation spectrum of amyotrophic lateral sclerosis in Central South China
Neurobiol Aging. 2021 Jun 19:S0197-4580(21)00202-5. doi: 10.1016/j.neurobiolaging.2021.06.008. Online ahead of print.ABSTRACTTo analyze the mutational spectrum of known ALS causative genes in China ALS patients. We comprehensively analyzed 51 ALS causative genes by combining different sequencing technologies in 753 unrelated ALS patients from Central South China. The mean age at onset (AAO) was 53.7±11.4 years. The AAO was earlier in the autosomal dominant (AD) ALS patients than in the sporadic ALS (sALS) patients. Bulbar onset was more frequent in females than in males. SOD1 was the most frequently mutated gene in ...
Source: Neurobiology of Aging - July 19, 2021 Category: Geriatrics Authors: Zhen Liu Yanchun Yuan Mengli Wang Jie Ni Wanzhen Li Ling Huang Yiting Hu Pan Liu Xiaorong Hou Xuan Hou Juan Du Ling Weng Ruxu Zhang Qi Niu Jianguang Tang Hong Jiang Lu Shen Beisha Tang Junling Wang Source Type: research

Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population
Neurobiol Aging. 2021 Jun 19:S0197-4580(21)00205-0. doi: 10.1016/j.neurobiolaging.2021.06.011. Online ahead of print.ABSTRACTOur previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD p...
Source: Neurobiology of Aging - July 19, 2021 Category: Geriatrics Authors: Hung-Li Wang Tu-Hsueh Yeh Ying-Zu Huang Yi-Hsin Weng Rou-Shayn Chen Chin-Song Lu Kuo-Chen Wei Yu-Chuan Liu Ying-Ling Chen Chao-Lang Chen Yu-Jie Chen Yan-Wei Lin Chia-Chen Hsu Chi-Han Chiu Ching-Chi Chiu Source Type: research

Hippocampal shape across the healthy lifespan and its relationship with cognition
This article is part of the Virtual Special Issue titled COGNITIVE NEU- ROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.PMID:34280848 | DOI:10.1016/j.neurobiolaging.2021.03.018 (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 19, 2021 Category: Geriatrics Authors: Aur élie Bussy Raihaan Patel Eric Plitman Stephanie Tullo Alyssa Salaciak Saashi A Bedford Sarah Farzin Marie-Lise B éland Vanessa Valiquette Christina Kazazian Christine L Tardif Gabriel A Devenyi M Mallar Chakravarty Source Type: research

Mutation spectrum of amyotrophic lateral sclerosis in Central South China
Neurobiol Aging. 2021 Jun 19:S0197-4580(21)00202-5. doi: 10.1016/j.neurobiolaging.2021.06.008. Online ahead of print.ABSTRACTTo analyze the mutational spectrum of known ALS causative genes in China ALS patients. We comprehensively analyzed 51 ALS causative genes by combining different sequencing technologies in 753 unrelated ALS patients from Central South China. The mean age at onset (AAO) was 53.7±11.4 years. The AAO was earlier in the autosomal dominant (AD) ALS patients than in the sporadic ALS (sALS) patients. Bulbar onset was more frequent in females than in males. SOD1 was the most frequently mutated gene in ...
Source: Neurobiology of Aging - July 19, 2021 Category: Geriatrics Authors: Zhen Liu Yanchun Yuan Mengli Wang Jie Ni Wanzhen Li Ling Huang Yiting Hu Pan Liu Xiaorong Hou Xuan Hou Juan Du Ling Weng Ruxu Zhang Qi Niu Jianguang Tang Hong Jiang Lu Shen Beisha Tang Junling Wang Source Type: research

Functional variant rs17525453 within RAB35 gene promoter is possibly associated with increased risk of Parkinson's disease in Taiwanese population
Neurobiol Aging. 2021 Jun 19:S0197-4580(21)00205-0. doi: 10.1016/j.neurobiolaging.2021.06.011. Online ahead of print.ABSTRACTOur previous study suggests that upregulated RAB35 is implicated in etiology of Parkinson's disease (PD). We hypothesized that upregulated RAB35 results from single nucleotide polymorphisms (SNPs) in RAB35 gene promoter. We identified SNPs within RAB35 gene promoter by analyzing DNA samples of discovery cohort and validation cohort. SNP rs17525453 within RAB35 gene promoter (T>C at position of -66) was significantly associated with idiopathic PD patients. Compared to normal controls, sporadic PD p...
Source: Neurobiology of Aging - July 19, 2021 Category: Geriatrics Authors: Hung-Li Wang Tu-Hsueh Yeh Ying-Zu Huang Yi-Hsin Weng Rou-Shayn Chen Chin-Song Lu Kuo-Chen Wei Yu-Chuan Liu Ying-Ling Chen Chao-Lang Chen Yu-Jie Chen Yan-Wei Lin Chia-Chen Hsu Chi-Han Chiu Ching-Chi Chiu Source Type: research

A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G & gt;T at the intron 9/exon 10 of the MAPT gene
This report of a second family with FTDP-17 associated with c.823-10G>T MAPT variant strongly supports pathogenicity of the variant and confirms it is a 4-repeat (4R) tauopathy. This intronic point mutation, probably strengthens the polypyrimidine tract and alters the splicing of exon 10 (10 nucleotides into intron 9) close to the 3' splice site.PMID:34274155 | DOI:10.1016/j.neurobiolaging.2021.05.010 (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 18, 2021 Category: Geriatrics Authors: Diana A Olszewska Conor Fearon Christopher McGuigan Terri P McVeigh Henry Houlden James M Polke Brian Lawlor Robert Coen Michael Hutchinson Michael Hutton Alan Beausang Isabelle Delon Francesca Brett Ioanna Sevastou Nuria Seto-Salvia Rohan de Silva Tim Ly Source Type: research

Cortical thinning is associated with brain pulsatility in older adults: An MRI and NIRS study
Neurobiol Aging. 2021 May 24;106:103-118. doi: 10.1016/j.neurobiolaging.2021.05.002. Online ahead of print.ABSTRACTAging is accompanied by global brain atrophy occurring unequally across the brain. Cortical thinning is seen with aging with a larger loss in the frontal and temporal subregions. We explored the link between regional cortical thickness and regional cerebral pulsatility. Sixty healthy individuals were divided into two age groups, young (aged 19-31) and older (aged 65-75) adults. Each participant underwent a near-infrared spectroscopy (NIRS) scan to index regional brain pulsatility from cerebral pulse-transit-ti...
Source: Neurobiology of Aging - July 18, 2021 Category: Geriatrics Authors: Hanieh Mohammadi Ke Peng Ali Kassab Anil Nigam Louis Bherer Fr édéric Lesage Yves Joanette Source Type: research

Relationship between inferior frontal sulcal hyperintensities on brain MRI, ageing and cerebral small vessel disease
Neurobiol Aging. 2021 Jun 21;106:130-138. doi: 10.1016/j.neurobiolaging.2021.06.013. Online ahead of print.ABSTRACTRaised signal in cerebrospinal fluid (CSF) on fluid-attenuated inversion recovery (FLAIR) may indicate raised CSF protein or debris and is seen in inferior frontal sulci on routine MRI. To explore its clinical relevance, we assessed the association of inferior frontal sulcal hyperintensities (IFSH) on FLAIR with demographics, risk factors, and small vessel disease markers in three cohorts (healthy volunteers, n=44; mild stroke patients, n=105; older community-dwelling participants from Lothian birth cohort 193...
Source: Neurobiology of Aging - July 18, 2021 Category: Geriatrics Authors: Jun-Fang Zhang Hwee Fang Lim Francesca M Chappell Una Clancy Stewart Wiseman Maria C Vald és-Hernández Daniela Jaime Garcia Mark E Bastin Fergus N Doubal Will Hewins Simon R Cox Susana Mu ñoz Maniega Michael Thrippleton Michael Stringer Charlotte Jardi Source Type: research

Pain processing in older adults with dementia-related cognitive impairment is associated with frontal neurodegeneration
This study examined whether differences in pressure pain sensitivity and endogenous pain inhibition (conditioned pain modulation (CPM)) between individuals with a dementia-related cognitive impairment (N=23) and healthy controls (N=35) are linked to dementia-related neurodegeneration. Pain was assessed via self-report ratings and by analyzing the facial expression of pain using the Facial Action Coding System. We found that cognitively impaired individuals show decreased CPM inhibition as assessed by facial responses compared to healthy controls, which was mediated by decreased gray matter volume in the medial orbitofronta...
Source: Neurobiology of Aging - July 18, 2021 Category: Geriatrics Authors: Steffie Bunk Sytse Zuidema Kathrin Koch Stefan Lautenbacher Peter P De Deyn Miriam Kunz Source Type: research

A recessive S174X mutation in Optineurin causes amyotrophic lateral sclerosis through a loss of function via allele-specific nonsense-mediated decay
Neurobiol Aging. 2021 Jun 4:S0197-4580(21)00170-6. doi: 10.1016/j.neurobiolaging.2021.05.009. Online ahead of print.ABSTRACTLoss of function (LoF) mutations in Optineurin can cause recessive amyotrophic lateral sclerosis (ALS) with some heterozygous LoF mutations associated with dominant ALS. The molecular mechanisms underlying the variable inheritance pattern associated with OPTN mutations have remained elusive. We identified that affected members of a consanguineous Middle Eastern ALS kindred possessed a novel homozygous p.S174X OPTN mutation. Analysis of these primary fibroblast lines from family members identified that...
Source: Neurobiology of Aging - July 17, 2021 Category: Geriatrics Authors: Marc Gotkine Martina de Majo Chun Hao Wong Simon D Topp Rachel Michaelson-Cohen Silvina Epsztejn-Litman Rachel Eiges Yossef Lerner Y Moein Kanaan Hagar Mor Shaked Nada Alahmady Caroline Vance Stephen J Newhouse Gerome Breen Agnes L Nishimura Christopher E Source Type: research

A recessive S174X mutation in Optineurin causes amyotrophic lateral sclerosis through a loss of function via allele-specific nonsense-mediated decay
Neurobiol Aging. 2021 Jun 4:S0197-4580(21)00170-6. doi: 10.1016/j.neurobiolaging.2021.05.009. Online ahead of print.ABSTRACTLoss of function (LoF) mutations in Optineurin can cause recessive amyotrophic lateral sclerosis (ALS) with some heterozygous LoF mutations associated with dominant ALS. The molecular mechanisms underlying the variable inheritance pattern associated with OPTN mutations have remained elusive. We identified that affected members of a consanguineous Middle Eastern ALS kindred possessed a novel homozygous p.S174X OPTN mutation. Analysis of these primary fibroblast lines from family members identified that...
Source: Neurobiology of Aging - July 17, 2021 Category: Geriatrics Authors: Marc Gotkine Martina de Majo Chun Hao Wong Simon D Topp Rachel Michaelson-Cohen Silvina Epsztejn-Litman Rachel Eiges Yossef Lerner Y Moein Kanaan Hagar Mor Shaked Nada Alahmady Caroline Vance Stephen J Newhouse Gerome Breen Agnes L Nishimura Christopher E Source Type: research

Cortical thickness in the right inferior frontal gyrus mediates age-related performance differences on an item-method directed forgetting task
Neurobiol Aging. 2021 Jun 23;106:95-102. doi: 10.1016/j.neurobiolaging.2021.06.001. Online ahead of print.ABSTRACTEvidence suggests that older adults have difficulty relative to younger adults in forgetting irrelevant information. Here we sought to understand the physical basis of this deficit by investigating the relationship between cortical thickness and intentional forgetting, using an item-method directed forgetting task. We tested younger (n = 44) and older (n = 54) adults' memories for words that they were instructed to either remember or to forget, and then extracted cortical thickness values from brain regions pre...
Source: Neurobiology of Aging - July 15, 2021 Category: Geriatrics Authors: Teal S Eich Patrick Lao Michael C Anderson Source Type: research

Cortical thickness in the right inferior frontal gyrus mediates age-related performance differences on an item-method directed forgetting task
Neurobiol Aging. 2021 Jun 23;106:95-102. doi: 10.1016/j.neurobiolaging.2021.06.001. Online ahead of print.ABSTRACTEvidence suggests that older adults have difficulty relative to younger adults in forgetting irrelevant information. Here we sought to understand the physical basis of this deficit by investigating the relationship between cortical thickness and intentional forgetting, using an item-method directed forgetting task. We tested younger (n = 44) and older (n = 54) adults' memories for words that they were instructed to either remember or to forget, and then extracted cortical thickness values from brain regions pre...
Source: Neurobiology of Aging - July 15, 2021 Category: Geriatrics Authors: Teal S Eich Patrick Lao Michael C Anderson Source Type: research

Prove pathogenicity of OPTN variants before establishing a causal relation with amyotrophic lateral sclerosis
Neurobiol Aging. 2021 Jun 18:S0197-4580(21)00193-7. doi: 10.1016/j.neurobiolaging.2020.10.035. Online ahead of print.NO ABSTRACTPMID:34253421 | DOI:10.1016/j.neurobiolaging.2020.10.035 (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 13, 2021 Category: Geriatrics Authors: J Finsterer F A Scorza C A Scorza A C Fiorini Source Type: research

Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan
We report two major findings: (1) Functional connectivity patterns during initiation, inhibition, and shifting were more similar in older ages, particularly for control and default networks, a pattern consistent with dedifferentiation of the neural correlates associated with cognitive control; and (2) Networks exhibited age-related reconfiguration such that frontal, default, and dorsal attention networks were more integrated whereas sub-networks of somato-motor system were more segregated in older age. Together these findings offer new evidence for dedifferentiation and reconfiguration of functional connectivity underlying...
Source: Neurobiology of Aging - July 13, 2021 Category: Geriatrics Authors: Jenny R Rieck Giulia Baracchini Daniel Nichol Herv é Abdi Cheryl L Grady Source Type: research

Prove pathogenicity of OPTN variants before establishing a causal relation with amyotrophic lateral sclerosis
Neurobiol Aging. 2021 Jun 18:S0197-4580(21)00193-7. doi: 10.1016/j.neurobiolaging.2020.10.035. Online ahead of print.NO ABSTRACTPMID:34253421 | DOI:10.1016/j.neurobiolaging.2020.10.035 (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 13, 2021 Category: Geriatrics Authors: J Finsterer F A Scorza C A Scorza A C Fiorini Source Type: research

Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan
We report two major findings: (1) Functional connectivity patterns during initiation, inhibition, and shifting were more similar in older ages, particularly for control and default networks, a pattern consistent with dedifferentiation of the neural correlates associated with cognitive control; and (2) Networks exhibited age-related reconfiguration such that frontal, default, and dorsal attention networks were more integrated whereas sub-networks of somato-motor system were more segregated in older age. Together these findings offer new evidence for dedifferentiation and reconfiguration of functional connectivity underlying...
Source: Neurobiology of Aging - July 13, 2021 Category: Geriatrics Authors: Jenny R Rieck Giulia Baracchini Daniel Nichol Herv é Abdi Cheryl L Grady Source Type: research

Prove pathogenicity of OPTN variants before establishing a causal relation with amyotrophic lateral sclerosis
Neurobiol Aging. 2021 Jun 18:S0197-4580(21)00193-7. doi: 10.1016/j.neurobiolaging.2020.10.035. Online ahead of print.NO ABSTRACTPMID:34253421 | DOI:10.1016/j.neurobiolaging.2020.10.035 (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 13, 2021 Category: Geriatrics Authors: J Finsterer F A Scorza C A Scorza A C Fiorini Source Type: research

Age- and gender-related differences in brain tissue microstructure revealed by multi-component T < sub > 2 < /sub > relaxometry
Neurobiol Aging. 2021 Jun 10;106:68-79. doi: 10.1016/j.neurobiolaging.2021.06.002. Online ahead of print.ABSTRACTIn spite of extensive work, inconsistent findings and lack of specificity in most neuroimaging techniques used to examine age- and gender-related patterns in brain tissue microstructure indicate the need for additional research. Here, we performed the largest Multi-component T2 relaxometry cross-sectional study to date in healthy adults (N = 145, 18-60 years). Five quantitative microstructure parameters derived from various segments of the estimated T2 spectra were evaluated, allowing a more specific interpretat...
Source: Neurobiology of Aging - July 12, 2021 Category: Geriatrics Authors: Erick Jorge Canales-Rodr íguez Silvia Alonso-Lana Norma Verdolini Salvador Sarr ó Isabel Feria Irene Montoro Beatriz Garcia-Ruiz Esther Jimenez Cristina Varo Auria Albacete Isabel Argila-Plaza Anna Lluch C Mar Bonnin Elisabet Vilella Eduard Vieta Edith Source Type: research

Analysis of PTRHD1 common and rare variants in European patients with Parkinson's disease
Neurobiol Aging. 2021 Jun 16:S0197-4580(21)00198-6. doi: 10.1016/j.neurobiolaging.2021.06.005. Online ahead of print.ABSTRACTThree studies in Iranian and African families identified three different variants in the peptidyl-tRNA hydrolase domain containing 1 gene (PTRHD1) in patients affected by parkinsonism with intellectual impairment. In the current study, our objective was to investigate whether PTRHD1 variants are associated with Parkinson's disease (PD) risk and age at onset (AAO). To evaluate the association between PTRHD1 and PD risk, we analyzed whole genome sequencing data of 1647 PD cases and 1050 healthy control...
Source: Neurobiology of Aging - July 11, 2021 Category: Geriatrics Authors: Yuri L Sosero Sara Bandres-Ciga Ziv Gan-Or Lynne Krohn IPDGC Source Type: research

Age-related dedifferentiation and hyperdifferentiation of perceptual and mnemonic representations
Neurobiol Aging. 2021 Jun 7;106:55-67. doi: 10.1016/j.neurobiolaging.2021.05.021. Online ahead of print.ABSTRACTPreliminary evidence indicates that occipito-temporal activation patterns for different visual stimuli are less distinct in older (OAs) than younger (YAs) adults, suggesting a dedifferentiation of visual representations with aging. Yet, it is unclear if this deficit (1) affects only sensory or also categorical aspects of representations during visual perception (perceptual representations), and (2) affects only perceptual or also mnemonic representations. To investigate these issues, we fMRI-scanned YAs and OAs v...
Source: Neurobiology of Aging - July 11, 2021 Category: Geriatrics Authors: Lifu Deng Simon W Davis Zachary A Monge Erik A Wing Benjamin R Geib Alex Raghunandan Roberto Cabeza Source Type: research

Analysis of PTRHD1 common and rare variants in European patients with Parkinson's disease
Neurobiol Aging. 2021 Jun 16:S0197-4580(21)00198-6. doi: 10.1016/j.neurobiolaging.2021.06.005. Online ahead of print.ABSTRACTThree studies in Iranian and African families identified three different variants in the peptidyl-tRNA hydrolase domain containing 1 gene (PTRHD1) in patients affected by parkinsonism with intellectual impairment. In the current study, our objective was to investigate whether PTRHD1 variants are associated with Parkinson's disease (PD) risk and age at onset (AAO). To evaluate the association between PTRHD1 and PD risk, we analyzed whole genome sequencing data of 1647 PD cases and 1050 healthy control...
Source: Neurobiology of Aging - July 11, 2021 Category: Geriatrics Authors: Yuri L Sosero Sara Bandres-Ciga Ziv Gan-Or Lynne Krohn IPDGC Source Type: research

Age-related dedifferentiation and hyperdifferentiation of perceptual and mnemonic representations
Neurobiol Aging. 2021 Jun 7;106:55-67. doi: 10.1016/j.neurobiolaging.2021.05.021. Online ahead of print.ABSTRACTPreliminary evidence indicates that occipito-temporal activation patterns for different visual stimuli are less distinct in older (OAs) than younger (YAs) adults, suggesting a dedifferentiation of visual representations with aging. Yet, it is unclear if this deficit (1) affects only sensory or also categorical aspects of representations during visual perception (perceptual representations), and (2) affects only perceptual or also mnemonic representations. To investigate these issues, we fMRI-scanned YAs and OAs v...
Source: Neurobiology of Aging - July 11, 2021 Category: Geriatrics Authors: Lifu Deng Simon W Davis Zachary A Monge Erik A Wing Benjamin R Geib Alex Raghunandan Roberto Cabeza Source Type: research

Apolipoprotein E4, amyloid, and cognition in Alzheimer's and Lewy body disease
In conclusion, the impact of APOE4 on disease risk depends on its effects on β-amyloid deposition, and APOE4 is associated with β-amyloid deposition regardless of the clinical diagnosis. However, it interacts with typical LBD to cause occipital β-amyloid deposition.PMID:34242895 | DOI:10.1016/j.neurobiolaging.2021.06.004 (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 9, 2021 Category: Geriatrics Authors: Jin Ho Jung Seun Jeon Kyoungwon Baik Yang Hyun Lee Seok Jong Chung Han Soo Yoo Seong Ho Jeong Young H Sohn Phil Hyu Lee Byoung Seok Ye Source Type: research

Apolipoprotein E4, amyloid, and cognition in Alzheimer's and Lewy body disease
In conclusion, the impact of APOE4 on disease risk depends on its effects on β-amyloid deposition, and APOE4 is associated with β-amyloid deposition regardless of the clinical diagnosis. However, it interacts with typical LBD to cause occipital β-amyloid deposition.PMID:34242895 | DOI:10.1016/j.neurobiolaging.2021.06.004 (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 9, 2021 Category: Geriatrics Authors: Jin Ho Jung Seun Jeon Kyoungwon Baik Yang Hyun Lee Seok Jong Chung Han Soo Yoo Seong Ho Jeong Young H Sohn Phil Hyu Lee Byoung Seok Ye Source Type: research