International Review of Psychiatry, December 2013; 25(6): 647–649
EDITORIAL
Int Rev Psychiatry Downloaded from informahealthcare.com by Universitat de Girona on 01/19/15 For personal use only.
Prospective cohort studies in dementia Although we have learned much from cross-sectional studies comparing people with dementia to those free of the syndrome, because most dementias evolve slowly (Ames et al., 2010) it is essential to undertake research which follows individuals over years to determine what factors pose a risk for the development of dementia or are protective against its incidence, and what variables modify the progression of cognitive impairment once it becomes manifest. These studies can also demonstrate the sequence and extent of biomarker changes as cognition declines, and in particular which biomarkers lie most proximal to dementia onset. It is realistic to hope and to expect that one day we will be able to calculate a risk profile for an individual and advise them of the likelihood that they will or will not develop dementia at a particular point in the future. If we are able to develop safe and effective disease modifying interventions for the commoner forms of dementia it might then be possible to offer such interventions to people at highest risk, so that we could delay or even prevent the onset of dementia in their remaining years of life. Critical to this is an understanding of when in the life course do risk factors impact upon the genesis or acceleration of disease and, accordingly, when is the best time to intervene? Both editors of this issue have had considerable experience in dementia research from at least a clinical and epidemiological perspective. When we were asked to prepare this special issue of the International Review of Psychiatry we decided to focus upon evidence from cohort studies and contacted people leading most of the important current and recently completed prospective studies of dementia and cognitive impairment which we knew to be occurring worldwide. Not all were in a position to provide an overview of their work by the deadline date we had chosen, but here in this issue we have ten papers which, given the high and rising prevalence of dementia (Ames et al., 2010) should be of interest to all the journal’s readers and of particular use to those undertaking research on dementia and cognitive decline. We think that several of these valuable summary and review articles will be cited frequently over the next few years.
ISSN 0954–0261 print/ISSN 1369–1627 online © 2013 Institute of Psychiatry DOI: 10.3109/09540261.2013.872954
The issue is bookended by two review articles, with another interleaved among seven accounts of prospective research studies. As Alzheimer’s disease is by far the commonest cause of dementia (Berr et al., 2005) it is appropriate that we open with a review article by Sona et al. examining the factors that have been shown to predict rapid (as opposed to slower) decline for individuals diagnosed with dementia due to Alzheimer’s disease. Although the literature is copious it yields disappointingly few clues about factors that accelerate or retard the progression of symptomatic Alzheimer’s disease. Younger, better educated and more impaired patients seem to go downhill faster on the measures assessed in studies. The last of these may be an epiphenomenon related to the scoring characteristics of the Mini-Mental State Examination (Folstein et al., 1975), and perhaps some other measures of dementia severity, which appear to exhibit sinusoidal decline curves in most people with Alzheimer’s dementia (Burns et al., 1991), while the second may reflect some aspect of cognitive reserve protecting individuals from exhibiting symptoms as early as those with less reserve (Stern et al., 1999), but clearly we need more and better conducted studies to refine our understanding of the phenomenon of decline, so that we can give better prognostic advice to those diagnosed with Alzheimer’s disease and their families. Findings from the Australian Imaging and Biomarkers Lifestyle (AIBL) study of ageing that indicated a more rapid decline in those subjects diagnosed with Alzheimer’s dementia who were taking cholinesterase inhibitors (Sona et al., 2012) alarmed those of us involved in their collection and interpretation at first, but are paralleled by an earlier report from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) by Schneider and colleagues (2011) and may be a consequence of a too early and injudicious ‘treatment’ with cholinesterase inhibitors (Ritchie & Zhinchin, 2013). The finding may simply reflect the propensity of doctors to prescribe treatment more often to those who are clearly declining, but reports from other cohorts confirming or refuting these observations are needed urgently.
Int Rev Psychiatry Downloaded from informahealthcare.com by Universitat de Girona on 01/19/15 For personal use only.
648
Editorial
Our second paper, by Hoe and colleagues, gives an overview of the London and South East Region Alzheimer’s Disease study (LASER-AD). By focusing upon carers as well as patients, this body of research has added valuable knowledge which can be used directly to benefit those with Alzheimer’s dementia and their families straight away. Neuropsychiatric symptoms, carer anxiety and depression, and abuse of those with Alzheimer’s dementia all are quite common and could be helped at once by better services and support. While the finding that survival of those with Alzheimer’s dementia was not directly related to the consumption of antipsychotic or antidepressant medication is reassuring, this should not be interpreted as indicating a need for lowered vigilance and caution in the prescribing of these medications to people with Alzheimer’s dementia. Evidence for efficacy indicates modest or no benefit for these treatments (Bains et al., 2002; Brodaty et al., 2003; Banerjee et al., 2011) and even if they are not directly associated with earlier death in this cohort, their potential to affect quality of life by causing side effects such as Parkinsonism or sedation, should not be overlooked. Even if the rural non-smoking, non-drinking Mormon population of Cache county Utah is not typical of that of the entire USA, the thorough observation of 5,000 older people by a group of dedicated researchers over more than a decade has yielded a treasure trove of useful data. In our third paper Tschanz and colleagues summarize the findings of their research. Of many results reported, the one that strikes us as significant parallels that of the LASER-AD study – even among these self-disciplined and superego-driven religiose older citizens, the cross-sectional prevalence of neuropsychiatric symptoms of significance is around two thirds of those found to have Alzheimer’s dementia. Neuropsychiatric symptoms are so common in Alzheimer’s disease that they should be expected to affect most individuals with dementia due to Alzheimer’s disease at some point in their illness and we should devote an appropriate amount of research to understanding them better, especially how to diminish their adverse consequences for patients and carers, without causing more damage than good. Our colleagues at the INSERM unit in Montpelier, France have contributed greatly to our understanding of the frequency, significance and evolution of a range of psychiatric and cognitive symptoms and syndromes in late life via a host of studies reported over the last two decades. For this issue of the International Review of Psychiatry Mortamais et al. have reviewed existing literature on cerebral white matter hyperintensities (WMH) seen on cerebral MRI scans, and their utility in the prediction of incident cognitive decline and frank dementia in later life. Although
modulated by cognitive reserve, age and the spatial distribution of lesions, WMH do appear to be early predictors of dementia risk, though additional research is needed in order to elucidate the extent to which they reflect vascular risk alone or are the result of other co-occurring morbidities. The AIBL study has now been running for over 7 years and research on this cohort of 1,112 individuals has produced over 100 peer reviewed papers on aspects of Alzheimer’s disease and cognitive decline in late life to date. In this issue Ellis et al. review imaging, biomarker, diet and lifestyle, and cognitive findings from this large collaborative venture. Perhaps the most salient contribution of the AIBL study has been to refine our understanding of the relationship between amyloid deposition in the brain and the phenomenon of cognitive decline (Rowe & Villemagne, 2011) and to highlight the steady but very slow rate at which amyloid pathology develops in the brain (Villemagne et al., 2013) and thus to indicate that there may well be a quite large temporal window in which anti-amyloid interventions could be applied to at-risk individuals, well before cognitive decline becomes manifest. At the same time as the AIBL study has been accumulating data, researchers in Australia’s other main capital city, Sydney, have been running an equally important project – the Sydney Memory and Ageing Study (MAS) whose findings are summarized for this issue by Tsang et al. Drawing its subjects from an epidemiologically derived rather than a convenience cohort, the MAS found high rates of mild cognitive impairment (MCI), though these varied according to the criteria which were employed for diagnosis, and highlighted an association between inflammatory markers, plasma apolipoprotein levels and subtle cognitive difficulty. WMH, sulcal morphology and tractography were identified as biomarkers of early cognitive decline. This well-designed and meticulously conducted study will add greatly to our knowledge over the next few years. Our seventh paper, by Szoeke et al., emphasizes the value to be gained by following cohorts of individuals for very long periods of time. The Women’s Healthy Ageing Project (WHAP) started in the early 1990s as a study of women experiencing the menopausal transition and now has over a decade’s worth of cognitive data and is undertaking amyloid imaging on up to 400 of these women in order better to understand factors affecting the early pathogenesis of dementia in general and AD in particular. Twins represent a unique resource to assist the unravelling of genetic and environmental factors which may influence cognition as people age. Sachdev and others report here on successive waves of observation on 623 individuals in three Australian states (including 161 monozygotic and 124 dizygotic twin
Int Rev Psychiatry Downloaded from informahealthcare.com by Universitat de Girona on 01/19/15 For personal use only.
Editorial pairs) which support the cognitive reserve hypothesis and assist understanding of the (apparently substantial) contribution of inheritance to a range of cognitive functions. It is all very well to observe the world, but the main reason that most medical research is done is to help us change it for the better, and bearing in mind that one can only determine the length of a river by finding its source, the genesis point of neurodegenerative disease can only be found by seeking disease in (at least) mid life. In our ninth contribution Ritchie and others report on an ambitious six stage programme which aims to decrease dementia incidence by characterizing risk, describing biomarker and cognitive expression of risk and applying secondary prevention strategies to people in mid life (aged 40–59) and then following them for long periods of time. We will be hearing a lot more about this study in the years ahead, even though it is likely that its completion will require oversight by more than one generation of researchers. The issue closes with another review. Individuals affected by intellectual disability (ID), especially Down’s syndrome (Ames et al., 2010) are at heightened risk of dementia as they age for what may be a range of factors including lifestyle and co-morbid disorders as well as their genetic endowment. Evans and colleagues have done a valuable job in reviewing the existing literature in this area and highlighting the ways in which future research should focus on the challenge of helping such people and what we can learn from them that may be applied more generally. Working with the ten groups who have contributed to this issue has been a pleasure and a privilege for both of us in our role as guest editors. We thank them and the colleagues who undertook rapid peer review of these articles so that they could be published as quickly as possible after receipt. We hope that others will find that they learn nearly as much from reading this issue as we did from putting it together. We are grateful for the encouragement we have received from members of the editorial board of the International Review of Psychiatry, especially Constantine G. Lyketsos, and for the patience, assistance and perseverance of Gerd Halvorsen who helped us put this issue together and see it through from a gleam in the eye to the published articles you now see before you. David Ames Director of National Ageing Research Institute, University of Melbourne Professor of Ageing and Health, Royal Melbourne Hospital, Victoria, Australia E-mail: [email protected]
649
Craig W. Ritchie Senior Lecturer, Centre for Mental Health, Imperial College London, UK, R&D Director and Honorary Consultant Psychiatrist, West London Mental Health Trust Co-Director, London (Northwest) CLRN E-mail: [email protected] References Ames, D., Burns, A. & O’Brien, J.T. (2010). Dementia (4th ed.). London: Hodder Arnold. Bains, J., Birks, J.S. & Dening, T.R. (2002). The efficacy of antidepressants in the treatment of depression in dementia. Cochrane Database of Systematic Reviews, 4, CD003944. Banerjee, S., Hellier, J., Dewey, M., Romeo, R., Ballard, C., Baldwin, R., … Burns, A. (2011). Sertraline or mirtazapine for depression in dementia (HTA-SADD): A randomised, multi-centre, double-blind, placebo-controlled trial. Lancet, 378, 403–411. Berr, C., Wancata, J. & Ritchie, K. (2005). Prevalence of dementia in the elderly in Europe. European Neurospcyhopharmacology, 15, 463–471. Brodaty, H., Ames, D., Snowdon, J., Woodward, M., Kirwan, J., Clarnette, R., … Grossman, F. (2003). A randomized, placebocontrolled trial of risperidone for the treatment of aggression, agitation and psychosis of dementia. Journal of Clinical Psychiatry, 64, 134–143. Burns, A., Jacoby, R. & Levy, R. (1991). Progression of cognitive impairment in Alzheimer’s disease. Journal of the American Geriatrics Society, 39, 39–45. Folstein, M., Folstein S & McHugh, P. (1975). ‘Mini-Mental State’: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198. Ritchie, C.W. & Zhinchin, G. (2013). Low dose, high dose or no dose: Better prescribing of cholinesterase inhibitors for Alzheimer’s disease. Guest Editorial. International Psychogeriatrics, 25, 511–515. Rowe, C.C. & Villemagne, V. (2011). Brain amyloid imaging. Journal of Nuclear Medicine, 52, 1733–1740. Schneider, L., Insel, P. & Weiner, M. (2011). Treatment with cholinesterase inhibitors and memantine of patients in the Alzheimer’s Disease Neuroimaging Initiative. Archives of Neurology, 68, 58–66. Sona A., Zhang, P., Ames, D., Bush A.I., Lautenschlager, N.T., Martins, R.N., … Ellis, K.A. (2012). Predictors of rapid cognitive decline in Alzheimer’s disease: Results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing. International Psychogeriatrics, 24, 197–204. Stern, Y., Albert, M., Tang, M.X. & Tsai, W.Y. (1999). Rate of memory decline in Alzheimer’s disease is related to education and occupation: Cognitive reserve? Neurology, 53, 1942–1947. Villemagne, V., Burnham, S., Bourgeat, P., Brown, B., Ellis, K.A., Salvado, O., … Masters, C.L. (2013). Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurology, 12, 357–367.
EDITORIAL
Int Rev Psychiatry Downloaded from informahealthcare.com by Universitat de Girona on 01/19/15 For personal use only.
Prospective cohort studies in dementia Although we have learned much from cross-sectional studies comparing people with dementia to those free of the syndrome, because most dementias evolve slowly (Ames et al., 2010) it is essential to undertake research which follows individuals over years to determine what factors pose a risk for the development of dementia or are protective against its incidence, and what variables modify the progression of cognitive impairment once it becomes manifest. These studies can also demonstrate the sequence and extent of biomarker changes as cognition declines, and in particular which biomarkers lie most proximal to dementia onset. It is realistic to hope and to expect that one day we will be able to calculate a risk profile for an individual and advise them of the likelihood that they will or will not develop dementia at a particular point in the future. If we are able to develop safe and effective disease modifying interventions for the commoner forms of dementia it might then be possible to offer such interventions to people at highest risk, so that we could delay or even prevent the onset of dementia in their remaining years of life. Critical to this is an understanding of when in the life course do risk factors impact upon the genesis or acceleration of disease and, accordingly, when is the best time to intervene? Both editors of this issue have had considerable experience in dementia research from at least a clinical and epidemiological perspective. When we were asked to prepare this special issue of the International Review of Psychiatry we decided to focus upon evidence from cohort studies and contacted people leading most of the important current and recently completed prospective studies of dementia and cognitive impairment which we knew to be occurring worldwide. Not all were in a position to provide an overview of their work by the deadline date we had chosen, but here in this issue we have ten papers which, given the high and rising prevalence of dementia (Ames et al., 2010) should be of interest to all the journal’s readers and of particular use to those undertaking research on dementia and cognitive decline. We think that several of these valuable summary and review articles will be cited frequently over the next few years.
ISSN 0954–0261 print/ISSN 1369–1627 online © 2013 Institute of Psychiatry DOI: 10.3109/09540261.2013.872954
The issue is bookended by two review articles, with another interleaved among seven accounts of prospective research studies. As Alzheimer’s disease is by far the commonest cause of dementia (Berr et al., 2005) it is appropriate that we open with a review article by Sona et al. examining the factors that have been shown to predict rapid (as opposed to slower) decline for individuals diagnosed with dementia due to Alzheimer’s disease. Although the literature is copious it yields disappointingly few clues about factors that accelerate or retard the progression of symptomatic Alzheimer’s disease. Younger, better educated and more impaired patients seem to go downhill faster on the measures assessed in studies. The last of these may be an epiphenomenon related to the scoring characteristics of the Mini-Mental State Examination (Folstein et al., 1975), and perhaps some other measures of dementia severity, which appear to exhibit sinusoidal decline curves in most people with Alzheimer’s dementia (Burns et al., 1991), while the second may reflect some aspect of cognitive reserve protecting individuals from exhibiting symptoms as early as those with less reserve (Stern et al., 1999), but clearly we need more and better conducted studies to refine our understanding of the phenomenon of decline, so that we can give better prognostic advice to those diagnosed with Alzheimer’s disease and their families. Findings from the Australian Imaging and Biomarkers Lifestyle (AIBL) study of ageing that indicated a more rapid decline in those subjects diagnosed with Alzheimer’s dementia who were taking cholinesterase inhibitors (Sona et al., 2012) alarmed those of us involved in their collection and interpretation at first, but are paralleled by an earlier report from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) by Schneider and colleagues (2011) and may be a consequence of a too early and injudicious ‘treatment’ with cholinesterase inhibitors (Ritchie & Zhinchin, 2013). The finding may simply reflect the propensity of doctors to prescribe treatment more often to those who are clearly declining, but reports from other cohorts confirming or refuting these observations are needed urgently.
Int Rev Psychiatry Downloaded from informahealthcare.com by Universitat de Girona on 01/19/15 For personal use only.
648
Editorial
Our second paper, by Hoe and colleagues, gives an overview of the London and South East Region Alzheimer’s Disease study (LASER-AD). By focusing upon carers as well as patients, this body of research has added valuable knowledge which can be used directly to benefit those with Alzheimer’s dementia and their families straight away. Neuropsychiatric symptoms, carer anxiety and depression, and abuse of those with Alzheimer’s dementia all are quite common and could be helped at once by better services and support. While the finding that survival of those with Alzheimer’s dementia was not directly related to the consumption of antipsychotic or antidepressant medication is reassuring, this should not be interpreted as indicating a need for lowered vigilance and caution in the prescribing of these medications to people with Alzheimer’s dementia. Evidence for efficacy indicates modest or no benefit for these treatments (Bains et al., 2002; Brodaty et al., 2003; Banerjee et al., 2011) and even if they are not directly associated with earlier death in this cohort, their potential to affect quality of life by causing side effects such as Parkinsonism or sedation, should not be overlooked. Even if the rural non-smoking, non-drinking Mormon population of Cache county Utah is not typical of that of the entire USA, the thorough observation of 5,000 older people by a group of dedicated researchers over more than a decade has yielded a treasure trove of useful data. In our third paper Tschanz and colleagues summarize the findings of their research. Of many results reported, the one that strikes us as significant parallels that of the LASER-AD study – even among these self-disciplined and superego-driven religiose older citizens, the cross-sectional prevalence of neuropsychiatric symptoms of significance is around two thirds of those found to have Alzheimer’s dementia. Neuropsychiatric symptoms are so common in Alzheimer’s disease that they should be expected to affect most individuals with dementia due to Alzheimer’s disease at some point in their illness and we should devote an appropriate amount of research to understanding them better, especially how to diminish their adverse consequences for patients and carers, without causing more damage than good. Our colleagues at the INSERM unit in Montpelier, France have contributed greatly to our understanding of the frequency, significance and evolution of a range of psychiatric and cognitive symptoms and syndromes in late life via a host of studies reported over the last two decades. For this issue of the International Review of Psychiatry Mortamais et al. have reviewed existing literature on cerebral white matter hyperintensities (WMH) seen on cerebral MRI scans, and their utility in the prediction of incident cognitive decline and frank dementia in later life. Although
modulated by cognitive reserve, age and the spatial distribution of lesions, WMH do appear to be early predictors of dementia risk, though additional research is needed in order to elucidate the extent to which they reflect vascular risk alone or are the result of other co-occurring morbidities. The AIBL study has now been running for over 7 years and research on this cohort of 1,112 individuals has produced over 100 peer reviewed papers on aspects of Alzheimer’s disease and cognitive decline in late life to date. In this issue Ellis et al. review imaging, biomarker, diet and lifestyle, and cognitive findings from this large collaborative venture. Perhaps the most salient contribution of the AIBL study has been to refine our understanding of the relationship between amyloid deposition in the brain and the phenomenon of cognitive decline (Rowe & Villemagne, 2011) and to highlight the steady but very slow rate at which amyloid pathology develops in the brain (Villemagne et al., 2013) and thus to indicate that there may well be a quite large temporal window in which anti-amyloid interventions could be applied to at-risk individuals, well before cognitive decline becomes manifest. At the same time as the AIBL study has been accumulating data, researchers in Australia’s other main capital city, Sydney, have been running an equally important project – the Sydney Memory and Ageing Study (MAS) whose findings are summarized for this issue by Tsang et al. Drawing its subjects from an epidemiologically derived rather than a convenience cohort, the MAS found high rates of mild cognitive impairment (MCI), though these varied according to the criteria which were employed for diagnosis, and highlighted an association between inflammatory markers, plasma apolipoprotein levels and subtle cognitive difficulty. WMH, sulcal morphology and tractography were identified as biomarkers of early cognitive decline. This well-designed and meticulously conducted study will add greatly to our knowledge over the next few years. Our seventh paper, by Szoeke et al., emphasizes the value to be gained by following cohorts of individuals for very long periods of time. The Women’s Healthy Ageing Project (WHAP) started in the early 1990s as a study of women experiencing the menopausal transition and now has over a decade’s worth of cognitive data and is undertaking amyloid imaging on up to 400 of these women in order better to understand factors affecting the early pathogenesis of dementia in general and AD in particular. Twins represent a unique resource to assist the unravelling of genetic and environmental factors which may influence cognition as people age. Sachdev and others report here on successive waves of observation on 623 individuals in three Australian states (including 161 monozygotic and 124 dizygotic twin
Int Rev Psychiatry Downloaded from informahealthcare.com by Universitat de Girona on 01/19/15 For personal use only.
Editorial pairs) which support the cognitive reserve hypothesis and assist understanding of the (apparently substantial) contribution of inheritance to a range of cognitive functions. It is all very well to observe the world, but the main reason that most medical research is done is to help us change it for the better, and bearing in mind that one can only determine the length of a river by finding its source, the genesis point of neurodegenerative disease can only be found by seeking disease in (at least) mid life. In our ninth contribution Ritchie and others report on an ambitious six stage programme which aims to decrease dementia incidence by characterizing risk, describing biomarker and cognitive expression of risk and applying secondary prevention strategies to people in mid life (aged 40–59) and then following them for long periods of time. We will be hearing a lot more about this study in the years ahead, even though it is likely that its completion will require oversight by more than one generation of researchers. The issue closes with another review. Individuals affected by intellectual disability (ID), especially Down’s syndrome (Ames et al., 2010) are at heightened risk of dementia as they age for what may be a range of factors including lifestyle and co-morbid disorders as well as their genetic endowment. Evans and colleagues have done a valuable job in reviewing the existing literature in this area and highlighting the ways in which future research should focus on the challenge of helping such people and what we can learn from them that may be applied more generally. Working with the ten groups who have contributed to this issue has been a pleasure and a privilege for both of us in our role as guest editors. We thank them and the colleagues who undertook rapid peer review of these articles so that they could be published as quickly as possible after receipt. We hope that others will find that they learn nearly as much from reading this issue as we did from putting it together. We are grateful for the encouragement we have received from members of the editorial board of the International Review of Psychiatry, especially Constantine G. Lyketsos, and for the patience, assistance and perseverance of Gerd Halvorsen who helped us put this issue together and see it through from a gleam in the eye to the published articles you now see before you. David Ames Director of National Ageing Research Institute, University of Melbourne Professor of Ageing and Health, Royal Melbourne Hospital, Victoria, Australia E-mail: [email protected]
649
Craig W. Ritchie Senior Lecturer, Centre for Mental Health, Imperial College London, UK, R&D Director and Honorary Consultant Psychiatrist, West London Mental Health Trust Co-Director, London (Northwest) CLRN E-mail: [email protected] References Ames, D., Burns, A. & O’Brien, J.T. (2010). Dementia (4th ed.). London: Hodder Arnold. Bains, J., Birks, J.S. & Dening, T.R. (2002). The efficacy of antidepressants in the treatment of depression in dementia. Cochrane Database of Systematic Reviews, 4, CD003944. Banerjee, S., Hellier, J., Dewey, M., Romeo, R., Ballard, C., Baldwin, R., … Burns, A. (2011). Sertraline or mirtazapine for depression in dementia (HTA-SADD): A randomised, multi-centre, double-blind, placebo-controlled trial. Lancet, 378, 403–411. Berr, C., Wancata, J. & Ritchie, K. (2005). Prevalence of dementia in the elderly in Europe. European Neurospcyhopharmacology, 15, 463–471. Brodaty, H., Ames, D., Snowdon, J., Woodward, M., Kirwan, J., Clarnette, R., … Grossman, F. (2003). A randomized, placebocontrolled trial of risperidone for the treatment of aggression, agitation and psychosis of dementia. Journal of Clinical Psychiatry, 64, 134–143. Burns, A., Jacoby, R. & Levy, R. (1991). Progression of cognitive impairment in Alzheimer’s disease. Journal of the American Geriatrics Society, 39, 39–45. Folstein, M., Folstein S & McHugh, P. (1975). ‘Mini-Mental State’: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198. Ritchie, C.W. & Zhinchin, G. (2013). Low dose, high dose or no dose: Better prescribing of cholinesterase inhibitors for Alzheimer’s disease. Guest Editorial. International Psychogeriatrics, 25, 511–515. Rowe, C.C. & Villemagne, V. (2011). Brain amyloid imaging. Journal of Nuclear Medicine, 52, 1733–1740. Schneider, L., Insel, P. & Weiner, M. (2011). Treatment with cholinesterase inhibitors and memantine of patients in the Alzheimer’s Disease Neuroimaging Initiative. Archives of Neurology, 68, 58–66. Sona A., Zhang, P., Ames, D., Bush A.I., Lautenschlager, N.T., Martins, R.N., … Ellis, K.A. (2012). Predictors of rapid cognitive decline in Alzheimer’s disease: Results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing. International Psychogeriatrics, 24, 197–204. Stern, Y., Albert, M., Tang, M.X. & Tsai, W.Y. (1999). Rate of memory decline in Alzheimer’s disease is related to education and occupation: Cognitive reserve? Neurology, 53, 1942–1947. Villemagne, V., Burnham, S., Bourgeat, P., Brown, B., Ellis, K.A., Salvado, O., … Masters, C.L. (2013). Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurology, 12, 357–367.
