Association of gait and balance disorders with age-related white matter changes

Baezner, Hansjoerg; Blahak, Christian; Poggesi, Anna; Pantoni, Leonardo; Inzitari, Domenico; Chabriat, Hugues; Erkinjuntti, Timo; Fazekas, Franz; Ferro, José M.; Langhorne, Peter; O’Brien, John T.; Scheltens, Philip; Visser, Marieke C.; Wahlund, Lars‐Olof; Waldemar, Gunhild; Wallin, Anders; Hennerici, Michael G.

doi:10.1212/01.wnl.0000305959.46197.e6

Cited by 376 publications

(326 citation statements)

References 30 publications

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“…LADIS consistently demonstrated significant differences between the performance of patients with punctate changes when compared with those with early confluent and confluent changes with the latter always being most impaired. Such relationships were seen for all clinical correlates, including cognition [87], depression [86], gait and balance [4], as well as urinary incontinence [56]. Most importantly, early confluent and to a greater extent confluent white matter abnormalities predicted functional decline in activities of daily living during a relatively short observational period of 3 years [37].…”

Section: Risk Factors and Key Clinical Findingsmentioning

confidence: 91%

“…Abstract reasoning is also commonly affected, but patients only suffer from mild memory deficits [38] with slight recognition and cueing difficulties [16]. Motor disturbances affect gait, postural control, and urinary continence [4,35,36,56]. There exists a large inter-individual variability of the clinical presentation in subjects with white matter changes.…”

Section: Risk Factors and Key Clinical Findingsmentioning

confidence: 99%

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Heterogeneity in age-related white matter changes

et al. 2011

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White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of

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Section: Risk Factors and Key Clinical Findingsmentioning

confidence: 91%

Section: Risk Factors and Key Clinical Findingsmentioning

confidence: 99%

Heterogeneity in age-related white matter changes

et al. 2011

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“…However, functional disabilities could also result from high BP, possibly through the development of cardiovascular disease or cerebrovascular pathology such as stroke or white matter lesions. [46][47][48][49] This puts functional decline in a complex position; it may be a consequence of hypertension, and at the same time modify the association between hypertension and cardiovascular morbidity and mortality.…”

Section: Risk Of Functional Disabilitiesmentioning

confidence: 99%

Treatment of Hypertension in the Oldest Old

et al. 2014

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A n 88-year-old woman with chronic hypertension was seen in the internal/geriatric medicine outpatient clinic. She had been treated for high blood pressure (BP) for ≈20 years with a low-dose thiazide, to which an angiotensin-converting enzyme-inhibitor had been added 5 years ago. In addition, after a possible transient ischemic attack 10 years ago, aspirin, omeprazole, and simvastatin had been added. She is known with mild cognitive impairment, which is stable with a mini-mental state examination score of 25, and a mild depression for which fluoxetine has been prescribed. In addition, she experienced 2 falls in the past 2 years; calcium/vitamin D and alendronate were started for the management of osteoporosis. On physical examination, she appears vital with a normal fluent gait and no signs of hemiparesis. Her BP is 165/75 mm Hg in the sitting position. Immediately after standing up from her chair, she feels dizzy for ≈10 seconds, but after 1 and 3 minutes, no orthostatic hypotension is found. Estimated glomerular filtration rate is 50 mL/min per 1.73 m 2 . Should antihypertensive treatment be intensified, left unaltered, or reduced?The oldest old, that is, persons aged ≥80 years, will be the fastest growing segment of the population for the next 40 years. By 2050, more than one quarter of all men and women aged ≥65 years in the Western world will be in the oldest old group. 1Despite longer life expectancy, the prevalence of various chronic diseases and functional impairment increases with age. As a result, populations of older individuals are often highly heterogeneous and individuals with same chronological age vary widely in health and functional ability. In other words, there is substantial heterogeneity in their biological age, and those at the higher end of biological age are often referred to as vulnerable or frail.BP rises with age, and ≈80% of people in Western societies aged ≥80 years have hypertension.2 Their hypertension is commonly characterized by elevated systolic BP, with often normal or even low diastolic BP. The widened pulse pressure (PP) is a reflection of increased arterial stiffness. Despite the large body of evidence in middle-aged populations, the predictive value of high BP in this rapidly growing older population is still debated, as is the question of whether hypertension should be treated, and if so, how intensively. Importantly, the current paradigm of lower is better may not apply to (untreated or treated) BP in the oldest old.In this concise narrative review, we summarize evidence from observational studies and randomized clinical trials. We conclude that biological age/frailty is becoming an important criterion for treatment decisions. Finally, we address what we think are the most pressing research questions for the coming years. Pathophysiology of BP Regulation in the Oldest OldAlthough hypertension in the oldest old may reflect a longstanding condition, often it manifests itself as a de novo abnormality. Data from the Framingham Heart Study indicate that the majority of patient...

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“…88 In otherwise normal older adults, white matter abnormalities have been associated with subtle abnormalities of balance and gait. [89][90][91] As white matter changes are associated with motor dysfunction in otherwise normal elderly adults, comorbid leukoaraiosis could be predicted to contribute also to clinical features in PD. We recently reported that comorbid white matter disease is a greater determinant of axial motor impairment and stooped posture than nigrostriatal dopaminergic denervation in PD.…”

Section: Non-specific White Matter Degeneration and Impaired Balance mentioning

confidence: 99%

Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease

2011

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There is a need to explore non-dopaminergic approaches to treating balance and gait problems in PD. There is emerging evidence on the role of cholinergic denervation of the PPN-thalamus system and falls in PD. Preliminary clinical trial data suggest that the subgroup of PD patients with frequent falls may be suitable candidates for future cholinergic augmentation clinical trials. Recent controlled clinical trials using methylphenidate have been unable to confirm earlier reports of improved gait in PD. Although progressive deterioration of axial motor symptoms occur with DBS of the STN or GPi, new preliminary research suggests that other surgical stimulation sites, such as the PPN, may have a potential benefit on gait and balance impairments in PD. Ongoing vigorous exercise and physical fitness should be highly encouraged to patients with PD who are at risk of physical deconditioning and fear of falling but effective anti-fall physical therapy interventions remain an unmet clinical need.

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Association of gait and balance disorders with age-related white matter changes

Abstract: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk of limitations in mobility.

Cited by 376 publications

References 30 publications

Heterogeneity in age-related white matter changes

Heterogeneity in age-related white matter changes

Treatment of Hypertension in the Oldest Old

Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease

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