Longitudinal patterns of brain aging and neurodegeneration among older adults with dual decline in memory and gait

Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)

Опубликована: Фев. 1, 2025

Abstract INTRODUCTION Dual cognitive and mobility decline is more strongly associated with dementia risk than only. It remains unknown whether this syndrome brain atrophy patterns, white matter (WM) damage, or pathology. METHODS In the Baltimore Longitudinal Study of Aging participants without dual decline, we used linear mixed‐effects models to compare up 13‐year longitudinal changes in MRI‐derived WM hyperintensities ( n = 339), microstructure 307), plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta 42/40 (Aβ ) ratio 349), phosphorylated tau 181 (pTau181) 258). RESULTS Those experiencing showed accelerated medial temporal p .004), parietotemporal .029), perisylvian regions .028), whereas gait only .035) memory .021). was also unique microstructural deterioration several tracts < .05), a greater decrease Aβ .015), increases GFAP .009) NfL .001). DISCUSSION Individuals are at an increased for regional atrophy, degradation, biomarker‐defined molecular underlying dementia. Highlights patterns. deterioration. ratio. NfL. may indicate blood markers

Язык: Английский

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Plasma metabolomic signatures of dual decline in memory and gait in older adults

GeroScience, Год журнала: 2023, Номер 45(4), С. 2659 - 2667

Опубликована: Апрель 13, 2023

Abstract Older adults experiencing dual decline in memory and gait have greater dementia risk than those with or only, but mechanisms are unknown. Dual may indicate specific pathophysiological pathways to which can be reflected by circulating metabolites. We compared longitudinal changes plasma metabolite biomarkers of older without the Baltimore Longitudinal Study Aging (BLSA). Participants were grouped into 4 phenotypes based on annual rates verbal speed: no gait, decline. Repeated measures metabolomics measured biocrates p500 kit during same time assessments. In BLSA, 18 metabolites differed across groups ( q -value < 0.05). Metabolites differentially abundant enriched for lysophosphatidylcholines (lysoPC C18:0,C16:0,C17:0,C18:1,C18:2), ceramides (d18:2/24:0,d16:1/24:0,d16:1/23:0), amino acids (glycine) classes. Compared decline, group showed declines lysoPC C18:0, homoarginine synthesis, module containing mostly triglycerides, a increase indoleamine 2,3-dioxygenase (IDO) activity. distinguishing implicated metabolic aminoacyl-tRNA biosynthesis, valine, leucine isoleucine histidine metabolism, sphingolipid metabolism. exhibit most extensive alterations profiling lysoPCs, ceramides, IDO activity, synthesis. Alterations these mitochondrial dysfunction, compromised immunity, elevated burden cardiovascular kidney pathology.

Язык: Английский

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Navigating and diagnosing cognitive frailty in research and clinical domains

Nature Aging, Год журнала: 2023, Номер 3(11), С. 1325 - 1333

Опубликована: Окт. 16, 2023

Язык: Английский

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Altered cerebellar and caudate gray‐matter volumes and structural covariance networks preceding dual cognitive and mobility impairments in older people

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(4), С. 2420 - 2433

Опубликована: Фев. 1, 2024

Abstract INTRODUCTION The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray‐matter volumes (GMVs) structural covariance networks (SCNs) abnormalities in community‐based older people preceding the conversion to physio‐cognitive decline syndrome (PCDS). METHODS Voxel‐wise brain GMV established SCNs were compared between PCDS non‐PCDS converters. RESULTS study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact functions. Over average 5.6‐year follow‐up, 116 transitioned PCDS. Identified regions abnormal GMVs converters over cerebellum caudate, which served as seeds for establishment. Significant differences cerebellum‐based (to right frontal pole left middle gyrus) caudate‐based caudate putamen, planum temporale, precentral gyrus, postcentral parietal operculum) nonconverters observed. DISCUSSION This reveals early neuroanatomic changes, emphasizing cerebellum's role, dual impairments. Highlights Neuroanatomic precursors of impairments identified. Cerebellar reductions increased precede onset Altered cerebellum‐ drive transformation. research establishes a foundation understanding specific syndrome.

Язык: Английский

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Accelerated sarcopenia precedes learning and memory impairments in the P301S mouse model of tauopathies and Alzheimer's disease

Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2024, Номер 15(4), С. 1358 - 1375

Опубликована: Апрель 22, 2024

Abstract Background Alzheimer's disease (AD) impairs cognitive functions and peripheral systems, including skeletal muscles. The PS19 mouse, expressing the human tau P301S mutation, shows muscular pathologies, reflecting central atrophy seen in AD. Methods We analysed muscle morphology neuromuscular junction (NMJ) through immunohistochemistry advanced image quantification. A factorial Analysis of Variance assessed weight, NCAM expression, NMJ, myofibre type distribution, cross‐sectional areas, expression single or multiple myosin heavy‐chain isoforms, grouping wild (WT) mice over their lifespan (1–12 months). Results Significant weight differences extensor digitorum longus (EDL) soleus muscles between WT were noted by 7–8 months. For EDL females, weighed 0.0113 ± 0.0005 compared with PS19's 0.0071 0.0008 ( P < 0.05), males, was 0.0137 0.0001 versus 0.0069 0.0006 0.005). Similarly, showed significant differences; females (WT: 0.0084 0.0004; PS19: 0.0057 0.0005, 0.005) males 0.0088 0.0003; 0.0047 0.0004, 0.0001). NMJ revealed a marked reduction innervation at 5 months, further decline 10 pre‐terminals became shorter simpler showing steep Genotype age strongly influenced immunoreactivity, denoting denervation as early 5–6 months Type II fibres, earlier effects I fibres 3–4 Muscle subsequent linked to IIB IIA muscle, accompanied an increase hybrid fibres. fibre 1505 110 μm 2 1208 94 , 1731 185 1227 116 . demonstrated from 6 1194 52 858 62 1257 43 1030 55 Atrophy also affected IIX, + IIA, IIX both timeline for overall consistent, indicating simultaneous decline. Conclusions Progressive accelerated neurogenic sarcopenia may precede potentially predict deficits observed

Язык: Английский

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Mapping the neural substrate of high dual-task gait cost in older adults across the cognitive spectrum

Brain Structure and Function, Год журнала: 2025, Номер 230(1)

Опубликована: Янв. 4, 2025

Abstract The dual task cost of gait (DTC) is an accessible and cost-effective test that can help identify individuals with cognitive decline dementia. However, its neural substrate has not been widely described. This study aims to investigate the high DTC in older adults across spectrum decline. A total 336 from GAIT cohort were analyzed, including cognitively healthy (N = 122, 71 ± 3.6 years), those mild impairment 168, 5.3 dementia 46, 80 5.7 years). 20% or greater was considered indicate a level slowing down while performing successively two verbal tasks (counting backwards by ones naming animals). Voxel-based morphometry employed differences gray matter volume (GMV) between groups, which dichotomized according DTC. whole population 336) associated smaller GMV bilateral temporal lobe both dual-task conditions. moderation analysis compare status groups. revealed group exhibited additional cluster located left precentral gyrus loss animals DTC, contrast other These results provide new evidence on why capabilities deteriorate normal pathological aging. more precise understanding would elucidate use clinical research settings.

Язык: Английский

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Association between oral health and physio-cognitive decline syndrome of older adults in China and its sex differences: a cross-sectional study

BMC Geriatrics, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 28, 2025

Physio-Cognitive Decline Syndrome (PCDs) is characterized by the coexistence of MIND (mobility impairment, no disability) and CIND (cognitive dementia), which predicts dementia risk. Deteriorating oral health can contribute to malnutrition, cognitive decline, physical frailty, all may exacerbate PCDs symptoms. This study investigates association between PCDs, exploring sex differences in this relationship. A cross-sectional analysis baseline data from Nanjing Brain Health Cohort included 252 participants aged 60 older, assessing mobility (6-meter walk test, grip strength), function (MoCA), (natural teeth count, denture use, tongue lip motor function, masticatory swallowing ability, Oral Frailty Index). Logistic regression models were used examine associations PCDs. Among participants, 15.5% classified as having The odds lower with a higher number (OR = 0.939, 95% CI: 0.890–0.991, p 0.021), while impaired increased 3.811, 1.059–13.717, 0.041). In females, greater use. For males, frailty 5.202, 1.429–18.940, 0.012). Findings underscore significant among older adults, sex-specific effects. women, maintaining natural proper use are associated CIND, for men, linked Healthcare providers should consider incorporate strategies.

Язык: Английский

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Handgrip strength and gait speed relationships with cognitive impairment in Iranian older adults: Birjand longitudinal aging study

Geriatric Nursing, Год журнала: 2025, Номер 63, С. 280 - 287

Опубликована: Апрель 12, 2025

Язык: Английский

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Advanced brain age in community-dwelling population with combined physical and cognitive impairments

Neurobiology of Aging, Год журнала: 2023, Номер 130, С. 114 - 123

Опубликована: Июль 6, 2023

We investigated whether advanced brain biological age is associated with accelerated age-related physical and/or cognitive functional decline: mobility impairment no disability (MIND), dementia (CIND) and physio-cognitive decline syndrome (PCDS). constructed a brain-age prediction model using gray-matter features from the MRI of 1,482 healthy individuals (age: 18-92 years). Predicted chronological differences were obtained (brain-age-gap; BAG) analyzed in another 1,193 community-dwelling population aged ≥ 50 years. Among participants, there 501, 346, 148, 198 robust, CIND, MIND, PCDS groups, respectively. Participants had significantly larger BAG (BAG = 2.99±8.97) than robust -0.49±9.27, p 0.002; η2 0.014), CIND 0.47±9.16, 0.02; 0.01), MIND 0.36±9.69, 0.036; 0.013) groups. Advanced aging involved pathophysiology co-occurrence older people. The may be clinical phenotype reflective individuals. Data supporting present findings are available upon reasonable request.

Язык: Английский

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Correlated decline of cognitive and motor phenotypes and ADRD pathologies in old age

Alzheimer s & Dementia, Год журнала: 2023, Номер 19(9), С. 4150 - 4162

Опубликована: Июнь 12, 2023

Examining motor and cognitive decline in separate models may underestimate their associations.

Язык: Английский

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