Age-related White Matter Changes and Disability in the Elderly

Leonardo Pantoni, Anna Poggesi
European Psychiatric Review, 2008;1(2):55-58
pdf icon download pdf ejournal view ejournal

Abstract

Age-related white matter changes (ARWMCs), also called leukoaraiosis, are frequently found by neuroimaging in elderly patients with various clinical disturbances. The clinical relevance of ARWMCs has been extensively studied and better defined over the last decade. It has become quite clear that mild degrees of ARWMC are almost invariably found after the age of 65 years and should be considered part of the ageing process. On the other hand, moderate to severe degrees of ARWMCs are associated with cognitive, mood, gait and urinary disturbances interfering with everyday activities.

The European multicentre Leukoaraiosis And DISability (LADIS) study was started in order to assess whether ARWMC were associated with the transition to disability in autonomous patients over the age of 65 years. The study has provided corroboration of the clinical consequences of ARWMCs, and over the follow-up period has been able to show that patients with ARWMCs are at higher risk of becoming disabled, independent of the presence of other strong predictors of disability.
Keywords
White matter changes, disability, cognitive impairment, gait disturbances, elderly mood disorders
Disclosure The authors have no conflicts of interest to declare.
Received: April 18, 2008 Accepted May 15, 2008
Correspondence: Leonardo Pantoni, MD, PhD, Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. E: pantoni@neuro.unifi.it
Disability in the Elderly

Disability is a rather broad concept and can be defined as a condition judged to be significantly impaired relative to the usual standard of an individual. Disability in the elderly is the complex result of different processes, concurrent diseases and psychological and social factors. In terms of physical disability, the major underlying causes are chronic diseases, including acute events such as stroke and hip fracture, and slowly progressive diseases such as arthritis and heart disease.1 Elderly people with co-existent chronic diseases are at a higher risk of disability. As many chronic diseases are related to ageing, a vast number of elderly subjects will have to face disability at some point during their life. In Western countries, almost 75% of the elderly aged over 65 years have at least one chronic illness, and about 50% have at least two chronic illnesses.2

Despite data reporting a declining disability rate in some Western countries due to improvement of healthcare,3 it is likely that in many other geographical areas, particularly considering the ageing world population, the issue will remain a major societal problem. Loss of functionality in activities of daily living is associated with adverse outcomes and high healthcare costs. To explain the relationship between diseases and disability, various models have been proposed. Nagi4 proposed a conceptual model that sees active organ pathology or disease leading to anatomical, physiological, mental or emotional impairment, loss or abnormalities. Loss or abnormalities, in turn, would lead to functional limitations, resulting in disability. Besides demographic, lifestyle or psychosocial factors, various pathological conditions may initiate the chain of events leading to functional dependence in the elderly, but the full appreciation of their role remains to be better elucidated. This applies specifically to central nervous system diseases, because brain abnormalities are difficult to study. Imaging techniques may play a key role in this regard because they can disclose markers of brain pathology, possibly determining functional dependence in the elderly. Brain diseases may clinically present with cognitive disorders, walking and balance difficulties and mood and urinary disturbances. All these conditions are extremely common in the elderly and predict functional decline, dementia and disability.5–8

Interestingly, age-related white matter changes (ARWMCs) have been found retrospectively to be associated with each of the aforementioned disturbances (cognitive, mood, gait and urinary).9 ARWMCs, also called leukoaraiosis,10 are bilateral, patchy or confluent areas of hypodensity on computed tomography (CT), or hyperintensities on T2-weighted magnetic resonance images (MRI) found with high frequency by neuroimaging studies in the white matter of patients, mostly aged and with vascular factors. Longitudinal data have recently confirmed that ARWMCs predict motor performance decline,11 the onset of dementia12 and deterioration in selective cognitive domains.13

References:
  1. Fried LP, Guralnik JM, Disability in older adults: evidence regarding significance, etiology, and risk, J Am Geriatr Soc, 1997;45:92–100.
  2. Calkins E, Boult C, Wagner E, Pacala JTD (eds), New ways to care for older people, Building Systems Based on Evidence, New York: Springer, 1999.
  3. Cutler DM, Declining disability among the elderly, Health Aff (Millwood), 2001;20:11–27.
  4. Nagi S, Some conceptual issues in disability and rehabilitation, In: Sussman MB (ed.), Sociology and Rehabilitation, Washington, DC: American Sociological Association, 1965:100–113.
  5. Guralnik JM, Ferrucci L, Simonsick EM, et al., Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability, N Engl J Med, 1995;332:556–61.
  6. Di Carlo A, Baldereschi M, Amaducci L, et al., ILSA Working Group, Incidence of dementia, Alzheimer’s disease, and vascular dementia in Italy, The ILSA Study, J Am Geriatr Soc, 2002;50:41–8.
  7. Beekman AT, Copeland JR, Prince MJ, Review of community prevalence of depression in later life, Br J Psychiatry, 1999;174:307–11.
  8. Thom D, Variation in estimates of urinary incontinence prevalence in the community: effects of differences in definition, population characteristics, and study type, J Am Geriatr Soc, 1998;46:473–80.
  9. Kuo HK, Lipsitz LA, Cerebral white matter changes and geriatric syndromes: is there a link?, J Gerontol A Biol Sci Med Sci, 2004;59:818–26.
  10. Hachinski VC, Potter P, Merskey H, Leuko-araiosis, Arch Neurol, 1987;44:21–3.
  11. Rosano C, Kuller LH, Chung H, et al., Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults, J Am Geriatr Soc, 2005;53:649–54.
  12. Prins ND, van Dijk EJ, den Heijer T, et al., Cerebral white matter lesions and the risk of dementia, Arch Neurol, 2004;61:1531–4.
  13. Prins ND, van Dijk EJ, den Heijer T, et al., Cerebral smallvessel disease and decline in information processing speed, executive function and memory, Brain, 2005;128:2034–41.
  14. Schmidt R, Scheltens P, Erkinjuntti T, et al., for the European Task Force on Age-Related White Matter Changes, White matter lesion progression. A surrogate endpoint for trials in cerebral small vessel disease, Neurology, 2004;63:139–44.
  15. Pantoni L, Garcia JH, The significance of cerebral white matter abnormalities 100 years after Binswanger’s report: a review, Stroke, 1995;26:1293–1301.
  16. Pantoni L, Poggesi A, Inzitari D, The relation between white matter lesions and cognition, Curr Opin Neurol, 2007;20:390–97.
  17. Erkinjuntti T, Pantoni L, Scheltens P, Cooperation and networking on white matter disorders: the European Task Force on Age-Related White Matter Changes, Dement Geriatr Cogn Disord, 1998;9(Suppl. 1):44–5.
  18. Pantoni L, Basile AM, Pracucci G, et al., Impact of agerelated cerebral white matter changes on the transition to disability — the LADIS study: rationale, design and methodology, Neuroepidemiology, 2005;24:51–62.
  19. Lawton MP, Brody EM, Assessment of older people: selfmaintaining and instrumental activities of daily living, Gerontologist, 1969;9:179–86.
  20. Fazekas F, Chawluk JB, Alavi A, et al., MR signal abnormalities at 1.5T in Alzheimer’s dementia and normal aging, AJNR Am J Neuroradiol, 1987;8:421–6.
  21. Longstreth WT, Manolio TA, Arnold A, et al., Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3302 elderly people, The Cardiovascular Health Study, Stroke, 1996;27:1274–82.
  22. Gelinàs I, Gauthier L, McIntyre M, Gauthier S, Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia, Am J Occup Ther, 1999;53:471–81.
  23. The Euro-Qol Group, Euro-Qol: a new facility for the measurement of health-related quality of life, Health Policy, 1990;16:199–208.
  24. Folstein MF, Folstein SE, McHugh PR, “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician, J Psychiatr Res, 1975;12:189–98.
  25. McLeod CM, Half a century of research on the Stroop effect: an integrative review, Psychol Bull, 1991;109:163–203.
  26. Reitan RM, Validity of the Trail Making Test as an indicator of organic brain damage, Percept Mot Skills, 1958;8:271- 276.
  27. Ferris SH, General measures of cognition, Int Psychogeriatr, 2003;15(Suppl.1):215–17.
  28. Yesavage JA, Geriatric Depression Scale, Psychopharmacol Bull, 1988;24:709–11.
  29. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA, Cornell scale for depression in dementia, Biol Psychiatry, 1988;23:271–84.
  30. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), Washington (DC): American Psychiatric Association, 1994.
  31. Guralnik JM, Simonsick EM, Ferrucci L, et al., A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission, J Gerontol, 1994;49:M85-94.
  32. Guttmann CR, Benson R, Warfield SK, et al., White matter abnormalities in mobility-impaired older persons, Neurology, 2000;54:1277–83.
  33. Firback MJ, O’Brien JT, Pakrasi S, et al., on behalf of the LADIS group, White matter hyperinyensities and depression. Preliminary results from the LADIS study, Int J Geriatr Psychiatry, 2005;20:674–9.
  34. Krishnan MS, O’Brien JT, Firbank MJ, et al., on behalf of the LADIS group. Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study, Int J Geriatr Psychiatry, 2006;21:983–9.
  35. O’Brien JT, Firbank MJ, Krishnan MS, et al., on behalf of the LADIS group, White matter hyperintensities rather than lacunar infacts are associated with depressive symptoms in older people, The LADIS study, Am J Geriatr Psychiatry, 2006;14:834–41.
  36. Teodorczuk A, O’Brien JT, Firbank MJ, et al., LADIS Group, White matter changes and late-life depressive symptoms: longitudinal study, Br J Psychiatry, 2007;191:212–17.
  37. van der Flier WM, van Straaten ECW, Barkhof F, et al., on behalf of the LADIS study group, Small vessel disease and general cognitive function in non-disabled elderly: the LADIS study, Stroke, 2005;36:2116–20.
  38. van der Flier WM, van Straaten ECW, Barkhof F, et al., on behalf of the LADIS study group. Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly: the LADIS study, J Neurol Neurosurg Psychiatry, 2005;76:1497–1500.
  39. Verdelho A, Madureira S, Ferro JM, et al., LADIS Study, Differential impact of cerebral white matter changes, diabetes, hypertension and stroke on cognitive performance among non-disabled elderly. The LADIS study, J Neurol Neurosurg Psychiatry, 2007;78:1325–30.
  40. Baezner H, Blahak C, Poggesi A, et al., LADIS Study Group, Association of gait and balance disorders with age-related white matter changes: the LADIS study, Neurology, 2008;70:935–42.
  41. Pantoni L, Poggesi A, Basile AM, et al., on behalf of the LADIS Study Group, Leukoaraiosis predicts hidden global functioning impairment in nondisabled elderly. The LADIS (Leukoaraiosis and Disability in the Elderly) Study, J Am Geriatr Soc, 2006;54:1095–1101.
  42. Inzitari D, Simoni M, Pracucci G, et al., LADIS Study Group, Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study, Arch Intern Med, 2007;167:81–8.
close

This content is copyright protected

However, if you would like to share the information on this webpage, you may use the headline and link below:

Age-related White Matter Changes and Disability in the Elderly

Read more: Age-related White Matter Changes and Disability in the Elderly