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Article ; Online: Gray matter volume and within-task verbal fluency performance among older adults.

Pace, Brigitte / Holtzer, Roee / Wagshul, Mark E

2023 Volume 166, Page(s) 105960

Abstract: The current study examined the relationship between gray matter volume (GMV) and rate of word generation over the course of three consecutive 20-sec intervals in 60-sec letter and category verbal fluency (VF) tasks. Attenuated rate of within-person word ... ...

Abstract	The current study examined the relationship between gray matter volume (GMV) and rate of word generation over the course of three consecutive 20-sec intervals in 60-sec letter and category verbal fluency (VF) tasks. Attenuated rate of within-person word generation in VF provides incremental information beyond total scores and predicts increased risk of incident Mild Cognitive Impairment (MCI). No studies to date, however, have determined the structural neural substrates underlying word generation rate in VF. Participants were 70 community-residing adults ≥ 65 years, who completed the letter and category VF tasks and a 3 T structural MRI scan. Linear mixed effects models (LMEMs) were used to determine the moderating effect of GMV on word generation rate. Whole brain voxel-wise LMEMs, adjusted for age, gender, education, Wide-Range Achievement Test - reading subtest score (WRAT3), and global health score, were run using permutation methods to correct for multiple comparisons. Lower GMV, primarily in frontal regions (superior frontal, rostral middle frontal, frontal pole, medial orbitofrontal, and pars orbitalis), were related to attenuated word generation rate, especially for letter VF. We propose that lower frontal GMV underlies inefficient executive word search processes reflected by attenuated word generation slope in letter VF amongst older adults.
MeSH term(s)	Humans ; Aged ; Gray Matter/diagnostic imaging ; Verbal Behavior ; Brain/diagnostic imaging ; Cerebral Cortex ; Task Performance and Analysis ; Neuropsychological Tests
Language	English
Publishing date	2023-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603163-8
ISSN	1090-2147 ; 0278-2626
ISSN (online)	1090-2147
ISSN	0278-2626
DOI	10.1016/j.bandc.2023.105960
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Zs.A 1731: Show issues

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Article ; Online: Cortical thickness moderates intraindividual variability in prefrontal cortex activation patterns of older adults during walking.

Ross, Daliah / Wagshul, Mark E / Izzetoglu, Meltem / Holtzer, Roee

Journal of the International Neuropsychological Society : JINS

2023 Volume 30, Issue 2, Page(s) 117–127

Abstract: Objective: Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with ... ...

Abstract	Objective: Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with cognitive decline. Dual-task walking (DTW) performance in older adults has been related to cognition and neural integrity. We examined the hypothesis that reduced cortical thickness would be associated with greater increases in IIV in prefrontal cortex oxygenated hemoglobin (HbO Method: Participants were 55 healthy community-dwelling older adults (mean age = 74.84, standard deviation ( Results: Analyses revealed that thinner cortex in several regions was associated with greater increases in HbO Conclusions: Consistent with neural inefficiency, reduced cortical thickness in the PFC and throughout the cerebral cortex was associated with increases in HbO
MeSH term(s)	Humans ; Aged ; Prefrontal Cortex/diagnostic imaging ; Cerebral Cortex/diagnostic imaging ; Aging ; Cognition ; Walking
Language	English
Publishing date	2023-06-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1230632-0
ISSN	1469-7661 ; 1355-6177
ISSN (online)	1469-7661
ISSN	1355-6177
DOI	10.1017/S1355617723000371
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Zs.A 4440: Show issues

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Article ; Online: Caudate volume and symptoms of apathy in older adults with multiple sclerosis.

Cote, Sarah E / Wagshul, Mark E / Foley, Fredrick W / Lipton, Michael L / Holtzer, Roee

Multiple sclerosis (Houndmills, Basingstoke, England)

2023 Volume 29, Issue 10, Page(s) 1266–1274

Abstract: Background: Apathy is common in multiple sclerosis (MS) and neurological disease, but its presence and underlying brain mechanisms in older adults with MS (OAMS) have not been evaluated.: Objective: Examine apathy and its association with caudate ... ...

Abstract	Background: Apathy is common in multiple sclerosis (MS) and neurological disease, but its presence and underlying brain mechanisms in older adults with MS (OAMS) have not been evaluated. Objective: Examine apathy and its association with caudate nuclei volume in OAMS and controls. We hypothesized that compared to controls, OAMS would demonstrate: a) greater apathy; b) stronger associations between apathy and caudate nuclei volumes. Methods: OAMS ( Results: OAMS reported greater apathy compared to controls ( Conclusion: Caudate nuclei, which are susceptible to adverse MS effects and implicated in mediating cognitive and motor function, may influence the presence and severity of apathy in OAMS.
MeSH term(s)	Humans ; Aged ; Middle Aged ; Apathy ; Multiple Sclerosis/diagnosis ; Brain ; Caudate Nucleus/diagnostic imaging ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-08-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1290669-4
ISSN	1477-0970 ; 1352-4585
ISSN (online)	1477-0970
ISSN	1352-4585
DOI	10.1177/13524585231188096
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Zs.A 4428: Show issues

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Article ; Online: Brain control of dual-task walking can be improved in aging and neurological disease.

Holtzer, Roee / Choi, Jaeun / Motl, Robert W / Foley, Frederick W / Wagshul, Mark E / Hernandez, Manuel E / Izzetoglu, Meltem

GeroScience

2024 Volume 46, Issue 3, Page(s) 3169–3184

Abstract: The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the ... ...

Abstract	The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the prefrontal cortex, and compromised in multiple sclerosis and aging, predicts health outcomes. Whether acute practice can improve dual-task walking performance and prefrontal cortex hemodynamic response efficiency in multiple sclerosis has not been reported. To address this gap in the literature, the current study examined task- and practice-related effects on dual-task-walking and associated brain activation in older adults with multiple sclerosis and controls. Multiple sclerosis (n = 94, mean age = 64.76 ± 4.19 years) and control (n = 104, mean age = 68.18 ± 7.01 years) participants were tested under three experimental conditions (dual-task-walk, single-task-walk, and single-task-alpha) administered over three repeated counterbalanced trials. Functional near-infrared-spectroscopy was used to evaluate task- and practice-related changes in prefrontal cortex oxygenated hemoglobin. Gait and cognitive performances declined, and prefrontal cortex oxygenated hemoglobin was higher in dual compared to both single task conditions in both groups. Gait and cognitive performances improved over trials in both groups. There were greater declines over trials in oxygenated hemoglobin in dual-task-walk compared to single-task-walk in both groups. Among controls, but not multiple sclerosis participants, declines over trials in oxygenated hemoglobin were greater in dual-task-walk compared to single-task-alpha. Dual-task walking and associated prefrontal cortex activation efficiency improved during a single session, but improvement in neural resource utilization, although significant, was attenuated in multiple sclerosis participants. These findings suggest encouraging brain adaptability in aging and neurological disease.
MeSH term(s)	Humans ; Aged ; Walking/physiology ; Prefrontal Cortex/metabolism ; Aging/physiology ; Oxyhemoglobins/metabolism ; Multiple Sclerosis
Chemical Substances	Oxyhemoglobins
Language	English
Publishing date	2024-01-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-023-01054-3
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Zs.A 1502: Show issues

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Article ; Online: Frontal-striatal tract integrity and depression in older adults with and without multiple sclerosis.

Cote, Sarah E / Wagshul, Mark / Foley, Frederick W / Picone, Mary Anne / Lipton, Michael / Lee, Jimmy S / Holtzer, Roee

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2024

Abstract: ... prefrontal cortex to caudate nucleus (DLPFC-cn).: Results: OAMS reported significantly worse (i.e., higher ... that lower FA of the left DLPFC-pn was significantly associated with worse (i.e., higher) depression symptoms ...

Abstract	Objective: Lower white matter integrity of frontal-subcortical circuitry has been associated with late-life depression in normally aging older adults and with the presence of multiple sclerosis (MS). Frontal-striatal white matter tracts involved in executive, cognitive, emotion, and motor function may underlie depression in older adults with MS. The present study examined the association between depression score and frontal-striatal white matter integrity in older adults with MS and controls. Methods: Older adults with MS (OAMS) (n = 67, mean age = 64.55 ± 3.89) and controls (n = 74, mean age = 69.04 ± 6.32) underwent brain MRI, cognitive assessment, psychological, and motoric testing. Depression was assessed through the 30-item Geriatric Depression Scale. Fractional anisotropy (FA) was extracted from two bilateral tracts: dorsolateral prefrontal cortex to putamen nucleus (DLPFC-pn) and dorsolateral prefrontal cortex to caudate nucleus (DLPFC-cn). Results: OAMS reported significantly worse (i.e., higher) depression symptoms (β = .357, p < .001) compared to healthy controls. Adjusted moderation analyses revealed, via group by FA interactions, significantly stronger associations between FA of the left DLPFC-pn tract and total depression (B = - 61.70, p = .011) among OAMS compared to controls. Conditional effects revealed that lower FA of the left DLPFC-pn was significantly associated with worse (i.e., higher) depression symptoms (b = - 38.0, p = .028) only among OAMS. The other three tracts were not significant in moderation models. Conclusions: We provided first evidence that lower white matter integrity of the left DLPFC-pn tract was related to worse depression in older adults with MS.
Language	English
Publishing date	2024-01-30
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-024-07316-y
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Zs.A 1877: Show issues

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Article ; Online: Prefrontal cortex activation during dual-task walking in older adults is moderated by thickness of several cortical regions.

Ross, Daliah / Wagshul, Mark E / Izzetoglu, Meltem / Holtzer, Roee

GeroScience

2021 Volume 43, Issue 4, Page(s) 1959–1974

Abstract: Dual tasking, a defined facet of executive control processes, is subserved, in part, by the prefrontal cortex (PFC). Previous functional near-infrared spectroscopy (fNIRS) studies revealed elevated PFC oxygenated hemoglobin ( ... ...

Abstract	Dual tasking, a defined facet of executive control processes, is subserved, in part, by the prefrontal cortex (PFC). Previous functional near-infrared spectroscopy (fNIRS) studies revealed elevated PFC oxygenated hemoglobin (HbO
MeSH term(s)	Aged ; Executive Function ; Humans ; Oxyhemoglobins/metabolism ; Prefrontal Cortex/diagnostic imaging ; Prefrontal Cortex/metabolism ; Spectroscopy, Near-Infrared ; Walking
Chemical Substances	Oxyhemoglobins
Language	English
Publishing date	2021-06-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-021-00379-1
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Zs.A 1502: Show issues

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Article ; Online: Cortical thickness and hippocampal volume in adolescent children with obstructive sleep apnea.

Lee, Min-Hee / Sin, Sanghun / Lee, Seonjoo / Wagshul, Mark E / Zimmerman, Molly E / Arens, Raanan

Sleep

2022 Volume 46, Issue 3

Abstract: Study objectives: Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA ... ...

Abstract	Study objectives: Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA in overweight and obese adolescent children is associated with cortical thickness and hippocampal structure compared to overweight and obese controls and whether OSA severity is associated with measures of brain integrity. Methods: We calculated cortical thickness and hippocampal subfield volumes from T1-weighted images of 45 controls (age 15.43 ± 1.73 years, 21 male) and 53 adolescent children with OSA (age 15.26 ± 1.63 years, 32 male) to investigate the association of childhood OSA with the alteration of cortical structure and hippocampal subfield structural changes. In addition, we investigated the correlation between OSA severity and cortical thickness or hippocampal subfield volume using Pearson's correlation analysis. Results: We found cortical thinning in the right superior parietal area of adolescent children with OSA (cluster size 32.29 mm2, cluster-wise corrected p-value = .030) that was negatively correlated with apnea-hypopnea index (AHI) (R=-0.27, p-value = .009) and arousal index (R=-0.25, p-value = .014). In addition, the volume of the right subiculum-head area of the hippocampus of adolescent children with OSA was larger than controls (0.19 ± 0.02 ml vs. 0.18 ± 0.02 ml, β = 13.79, false discovery rate corrected p-value = .044), and it was positively correlated with AHI (R = 0.23, p-value = .026) and arousal index (R = 0.31, p-value = .002). Conclusions: Our findings provide evidence for OSA-associated brain structure alterations in adolescent children prior to the onset of treatment that likely have important implications for timely intervention and continued monitoring of health outcomes.
MeSH term(s)	Humans ; Male ; Adolescent ; Child ; Overweight ; Pediatric Obesity/complications ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/diagnostic imaging ; Brain ; Hippocampus/diagnostic imaging
Language	English
Publishing date	2022-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsac201
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Zs.A 1475: Show issues

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Article ; Online: Cognitive Reserve Moderates the Efficiency of Prefrontal Cortex Activation Patterns of Gait in Older Adults.

Holtzer, Roee / Ross, Daliah / O'Brien, Catherine / Izzetoglu, Meltem / Wagshul, Mark E

The journals of gerontology. Series A, Biological sciences and medical sciences

2021 Volume 77, Issue 9, Page(s) 1836–1844

Abstract: Background: Cognitive reserve (CR) protects against cognitive decline, but whether CR influences the efficiency of cortical control of gait has not been reported. The current study addressed this important gap in the literature. Specifically, we ... ...

Abstract	Background: Cognitive reserve (CR) protects against cognitive decline, but whether CR influences the efficiency of cortical control of gait has not been reported. The current study addressed this important gap in the literature. Specifically, we determined the role of CR in moderating the efficiency of functional near-infrared spectroscopy (fNIRS)-derived oxygenated hemoglobin (HbO2) in the prefrontal cortex (PFC) assessed during active walking. We hypothesized that higher CR would be associated with more efficient brain activation patterns. Methods: Participants were 55 (mean age = 74.84; %female = 49.1) older adults who underwent the combined walking/fNIRS protocol and had magnetic resonance imaging data. We used an established dual-task walking paradigm that consisted of 3 task conditions: single-task walk (STW), single-task alpha (STA, cognitive task), and dual-task walk (DTW). Using the residual approach, CR was derived from a word-reading test score by removing variance accounted for by sociodemographic variables, tests of current cognitive functions, and a measure of structural brain integrity. Results: CR moderated the change in fNIRS-derived HbO2 in the PFC across tasks. Higher CR was associated with smaller increases in fNIRS-derived HbO2 from the single tasks to dual-task walking (CR × DTW compared with STW: estimate = 0.183; p < .001; CR × DTW compared with STA: estimate = 0.257; p < .001). The moderation effect of CR remained significant when adjusting for multiple covariates and concurrent moderation effects of measures of gait performance, current cognitive functions, and structural integrity of the brain. Conclusion: The current study provided first evidence that higher CR was associated with better neural efficiency of walking in older adults.
MeSH term(s)	Aged ; Cognitive Reserve ; Female ; Gait/physiology ; Humans ; Oxyhemoglobins/metabolism ; Prefrontal Cortex/metabolism ; Spectroscopy, Near-Infrared/methods ; Walking/physiology
Chemical Substances	Oxyhemoglobins
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glab288
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Article ; Online: Altered cortical structure network in children with obstructive sleep apnea.

Lee, Min-Hee / Sin, Sanghun / Lee, Seonjoo / Park, Hyunbin / Wagshul, Mark E / Zimmerman, Molly E / Arens, Raanan

Sleep

2022 Volume 45, Issue 5

Abstract: Study objectives: Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse during sleep, resulting in intermittent hypoxia and sleep fragmentation that may contribute to alternations in brain structure and function. We hypothesized ... ...

Abstract	Study objectives: Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse during sleep, resulting in intermittent hypoxia and sleep fragmentation that may contribute to alternations in brain structure and function. We hypothesized that OSA in children reorganizes and alters cortical structure, which can cause changes in cortical thickness correlation between brain regions across subjects. Methods: We constructed cortical structure networks based on cortical thickness measurements from 41 controls (age 15.54 ± 1.66 years, male 19) and 50 children with OSA (age 15.32 ± 1.65 years, male 29). The global (clustering coefficient [CC], path length, and small-worldness) and regional (nodal betweenness centrality, NBC) network properties and hub region distributions were examined between groups. Results: We found increased CCs in OSA compared to controls across a wide range of network densities (p-value < .05) and lower NBC area under the curve in left caudal anterior cingulate, left caudal middle frontal, left fusiform, left transverse temporal, right pars opercularis, and right precentral gyri (p-value < .05). In addition, while most of the hub regions were the same between groups, the OSA group had fewer hub regions and a different hub distribution compared to controls. Conclusions: Our findings suggest that children with OSA exhibit altered global and regional network characteristics compared to healthy controls. Our approach to the investigation of cortical structure in children with OSA could prove useful in understanding the etiology of OSA-related brain functional disorders.
MeSH term(s)	Adolescent ; Brain ; Child ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Male ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/diagnostic imaging ; Sleep Deprivation
Language	English
Publishing date	2022-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsac030
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Zs.A 1475: Show issues

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Article ; Online: Differential Associations of Mobility With Fronto-Striatal Integrity and Lesion Load in Older Adults With and Without Multiple Sclerosis.

Wagshul, Mark E / Foley, Frederick W / Chaudhary, Kapil / Lipton, Michael L / Motl, Robert W / Izzetoglu, Meltem / Hernandez, Manuel E / Picone, Mary Ann / Holtzer, Roee

Neurorehabilitation and neural repair

2023 Volume 37, Issue 4, Page(s) 205–217

Abstract: Background: Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood.: Objective: Examine fronto-striatal ... ...

Abstract	Background: Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood. Objective: Examine fronto-striatal white matter (WM) integrity and lesion load as imaging correlates of mobility outcomes in older persons with and without MS. Methods: Fifty-one older MS patients (age 64.9 ± 3.7 years, 29 women) and 50 healthy, matched controls (66.2 ± 3.2 years, 24 women), participated in the study, which included physical and cognitive test batteries and 3T MRI imaging session. Primary imaging measures were fractional anisotropy (FA) and WM lesion load. The relationship between mobility impairment, defined using a validated short physical performance battery cutoff score, and neuroimaging measures was assessed with stratified logistic regression models. FA was extracted from six fronto-striatal circuits (left/right): dorsal striatum (dStr)-to-anterior dorsolateral prefrontal cortex (aDLPFC), dStr-to-posterior DLPFC, and ventral striatum (vStr)-to-ventromedial prefrontal cortex (VMPFC). Results: Mobility impairment was significantly associated with lower FA in two circuits, left dStr-aDLPFC ( Conclusions: Comparing older persons with and without MS, we provide compelling evidence of a double dissociation between the presence of mobility impairment and two neuroimaging markers of white matter integrity, fronto-striatal fractional anisotropy, and whole brain lesion load.
MeSH term(s)	Humans ; Female ; Aged ; Aged, 80 and over ; Middle Aged ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnostic imaging ; Brain/pathology ; Magnetic Resonance Imaging/methods ; Gray Matter/pathology ; White Matter/diagnostic imaging ; White Matter/pathology ; Anisotropy
Language	English
Publishing date	2023-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1491637-x
ISSN	1552-6844 ; 1545-9683 ; 0888-4390
ISSN (online)	1552-6844
ISSN	1545-9683 ; 0888-4390
DOI	10.1177/15459683231164787
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Zs.B 3096: Show issues

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