• A. J. Larner


This chapter examines various aspects of the management of cognitive disorders, including provision of information and pharmacotherapy, both licensed and novel treatments. The effects of a number of policy directives issued under the auspices of the United Kingdom government in recent years are examined: none appears to contribute to closure of the dementia diagnosis gap. The place of neurology-led services for dementia within an integrated dementia care pathway is considered.


Dementia Treatment Cholinesterase inhibitors National Dementia Strategy Integrated care pathway 


  1. Abernethy Holland AJ, Larner AJ. Central nervous system/brain tumour 2-week referral guidelines: prospective 3-year audit. Clin Oncol. 2008;20:201–2.PubMedCrossRefGoogle Scholar
  2. Abernethy Holland AJ, Larner AJ. Yttrium-90 implantation. Prog Neurol Psychiatry. 2009;13(5):27.Google Scholar
  3. AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet. 2004;363:2105–15.CrossRefGoogle Scholar
  4. Ahmadi-Abhari S, Guzman-Castillo M, Bandosz P, et al. Temporal trend in dementia incidence since 2002 and projections for prevalence in England and Wales to 2040. BMJ. 2017;358:j2856.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ali R, Barborie A, Larner AJ, White RP. Psychiatric presentation of sporadic Creutzfeldt-Jakob disease: a challenge to current diagnostic criteria. J Neuropsychiatry Clin Neurosci. 2013;25:335–8.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Alzheimer’s Society. Dementia UK. A report into the prevalence and cost of dementia prepared by the Personal Social Services Research Unit (PSSRU) at the London School of Economics and the Institute of Psychiatry at King’s College London, for the Alzheimer’s Society. London: Alzheimer’s Society; 2007.Google Scholar
  7. Alzheimer’s Society. Mapping the dementia gap: study produced by Tesco, Alzheimer’s Society and Alzheimer’s Scotland. London: Alzheimer’s Society; 2011.Google Scholar
  8. Alzheimer’s Society. Mapping the Dementia Gap 2012. Progress on improving diagnosis of dementia 2011–2012. London: Alzheimer’s Society; 2013.Google Scholar
  9. Alzheimer’s Society. Dementia UK—overview. 2nd ed. London: Alzheimer’s Society; 2014.Google Scholar
  10. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed., text revison (DSM-IV-TR). Washington: American Psychiatric Association; 2000.Google Scholar
  11. Atri A, Shaughnessy LW, Locascio JJ, Growdon JH. Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis Assoc Disord. 2008;22:209–21.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Banerjee S, Willis R, Matthews D, Contell F, Chan J, Murray J. Improving the quality of care for mild to moderate dementia: an evaluation of the Croydon Memory Service Model. Int J Geriatr Psychiatry. 2007;22:782–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Baum ML. The neuroethics of biomarkers. What the development of bioprediction means for moral responsibility, justice, and the nature of mental disorder. Oxford: Oxford University Press; 2016.CrossRefGoogle Scholar
  14. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005593.Google Scholar
  15. Birks J, Grimley Evans J. Ginkgo Biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2009;(1):CD003120.Google Scholar
  16. Bonello M, Larner AJ, Alusi SH. Myoclonus-dystonia (DYT11) with novel SGCE mutation misdiagnosed as a primary psychiatric disorder. J Neurol Sci. 2014;346:356–7.PubMedCrossRefGoogle Scholar
  17. Bowie P, Branton T, Holmes J. Should the Mini Mental State Examination be used to monitor dementia treatments? Lancet. 1999;354:1527–8.PubMedCrossRefGoogle Scholar
  18. British Medical Association. Revisions to the GMS Contract 2006/07. Delivering investment in general practice. London: British Medical Association; 2006.Google Scholar
  19. Brodaty H, Green A, Koschera A. Meta-analysis of psychosocial interventions of caregivers of people with dementia. J Am Geriatr Soc. 2003;51:657–64.PubMedCrossRefGoogle Scholar
  20. Brooke P, Bullock R. Validation of a 6 item cognitive impairment test with a view to primary care usage. Int J Geriatr Psychiatry. 1999;14:936–40.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Brunet MD, McCartney H, Heath I, et al. There is no evidence base for proposed dementia screening. BMJ. 2012;345:e8588.PubMedCrossRefGoogle Scholar
  22. Cagliarini AM, Price HL, Livemore ST, Larner AJ. Will use of the Six-Item Cognitive Impairment Test help to close the dementia diagnosis gap? Aging Health. 2013;9:563–6.CrossRefGoogle Scholar
  23. Campbell DT. Reforms as experiments. Am Psychol. 1969;24:409–29.CrossRefGoogle Scholar
  24. Campbell H, Hotchkiss R, Bradshaw N, Porteous M. Integrated care pathways. BMJ. 1998;316:133–7.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cannon P, Larner AJ. Errors in the scoring and reporting of cognitive screening instruments administered in primary care. Neurodegener Dis Manag. 2016;6:271–6.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chiu E. What’s in a name: dementia or dysmentia? Int J Geriatr Psychiatry. 1994;9:1–4.CrossRefGoogle Scholar
  27. Coleman LM, Fowler LL, Williams ME. Use of unproven therapies by people with Alzheimer’s disease. J Am Geriatr Soc. 1995;43:747–50.PubMedCrossRefGoogle Scholar
  28. Cruts M, van Duijn CM, Backhovens H, et al. Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet. 1998;7:43–51.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Curran S, Wattis JP, editors. Practical management of dementia: a multi-professional approach. 2nd ed. Oxford: Radcliffe Medical Press; 2011.Google Scholar
  30. Davey RJ, Jamieson S. The validity of using the mini mental state examination in NICE dementia guidelines. J Neurol Neurosurg Psychiatry. 2004;75:343–4.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Davies M, Larner AJ. Clinical misdiagnosis of Alzheimer’s disease: getting it wrong again. Eur J Neurol 2009;16(Suppl3):351 (abstract 2036).Google Scholar
  32. Davies M, Larner AJ. Frontotemporal dementias: development of an integrated care pathway through an experiential survey of patients and carers. Int J Care Pathways. 2010;14:65–9.CrossRefGoogle Scholar
  33. Department of Health. Transforming the quality of dementia care: consultation on a National Dementia Strategy. London: Department of Health; 2008.Google Scholar
  34. Department of Health. Living well with dementia: a National Dementia Strategy. London: Department of Health; 2009.Google Scholar
  35. Department of Health. Prime Minister’s Challenge on Dementia. Delivering major improvements in dementia care and research by 2015. London: Department of Health; 2012a.Google Scholar
  36. Department of Health. Using the Commissioning for Quality and Innovation (CQUIN) payment framework. Guidance on the new national goals 2012–13. London: Department of Health; 2012b.Google Scholar
  37. Department of Health. Prime Minister’s Challenge on Dementia 2020. London: Department of Health; 2015.Google Scholar
  38. Desikan RS, Fan CC, Wang Y, et al. Genetic assessment of age-associated Alzheimer disease risk: development and validation of a polygenic hazard score. PLoS Med. 2017;14(3):e1002258.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Diamond B, Johnson S, Torsney K, et al. Complementary and alternative medicines in the treatment of dementia: an evidence-based review. Drugs Aging. 2003;20:981–98.PubMedCrossRefGoogle Scholar
  40. Doody RS, Raman R, Farlow M, et al. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med. 2013;369:341–50.PubMedCrossRefGoogle Scholar
  41. Doran M, Larner AJ. Prominent behavioural and psychiatric symptoms in early-onset Alzheimer’s disease in a sib pair with the presenilin-1 gene R269G mutation. Eur Arch Psychiatry Clin Neurosci. 2004;254:187–9.PubMedCrossRefGoogle Scholar
  42. Doran M, Larner AJ. NICE/SCIE dementia guidance: time to reconsider. Adv Clin Neurosci Rehabil. 2008;8(1):34–5.Google Scholar
  43. Doran M, Harvie AK, Larner AJ. Antisocial behaviour orders: the need to consider underlying neuropsychiatric disease. Int J Clin Pract. 2006;60:861–2.PubMedCrossRefGoogle Scholar
  44. Dowd SB, Davidhizar R. Can mental and physical activities such as chess and gardening help in the prevention and treatment of Alzheimer’s? Healthy aging through stimulation of the mind. J Pract Nurs. 2003;53(3):11–3.PubMedGoogle Scholar
  45. Dubois B, Tolosa E, Katzenschlager R, et al. Donepezil in Parkinson’s disease dementia: a randomized, double-blind efficacy and safety study. Mov Disord. 2012;27:1230–8.PubMedCrossRefGoogle Scholar
  46. Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311:33–44.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Ellul J, Archer N, Foy CM, et al. The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration. J Neurol Neurosurg Psychiatry. 2007;78:233–9.PubMedCrossRefGoogle Scholar
  48. Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351:2509–18.PubMedCrossRefGoogle Scholar
  49. Erkinjuntti T, Roman G, Gauthier S, Feldman H, Rockwood K. Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke. 2004;35:1010–7.PubMedCrossRefGoogle Scholar
  50. Evans M, Ellis A, Watson D, et al. Sustained cognitive improvement following treatment of Alzheimer’s disease with donepezil. Int J Geriatr Psychiatry. 2000;15:50–3.PubMedCrossRefGoogle Scholar
  51. Farlow M, Potkin S, Koumaras B, Veach J, Mirski D. Analysis of outcome in retrieval dropout patients in a rivastigmine vs placebo, 26-week, Alzheimer disease trial. Arch Neurol. 2003;60:843–8.PubMedCrossRefGoogle Scholar
  52. Fearn S, Larner AJ. Have Quality and Outcomes Framework Depression Indicators changed referrals from primary care to a dedicated memory clinic? Ment Health Fam Med. 2009;6:129–32.Google Scholar
  53. Feldman HH, Ferris S, Winblad B, et al. Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study. Lancet Neurol. 2007;6:501–12.PubMedCrossRefGoogle Scholar
  54. Feldman HH, Pirttila T, Dartigues JF, et al. Treatment with galantamine and time to nursing home placement in Alzheimer’s disease patients with and without cerebrovascular disease. Int J Geriatr Psychiatry. 2008;24:479–88.CrossRefGoogle Scholar
  55. Ferrante di Ruffano L, Hyde CJ, McCaffery KJ, Bossuyt PM, Deeks JJ. Assessing the value of diagnostic tests: a framework for designing and evaluating trials. BMJ. 2012;344:e686.PubMedCrossRefGoogle Scholar
  56. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112–7.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Fisher CAH, Larner AJ. Frequency and diagnostic utility of cognitive test instrument use by general practitioners prior to memory clinic referral. Fam Pract. 2007;24:495–7.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Friedland RP, Fritsch T, Smyth KA, et al. Patients with Alzheimer’s disease have reduced activities in midlife compared with healthy control group members. Proc Natl Acad Sci U S A. 2001;98:3440–5.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Gale TM, Larner AJ. Six-Item Cognitive Impairment Test (6CIT). In: Larner AJ, editor. Cognitive screening instruments. A practical approach. 2nd ed. London: Springer; 2017. p. 241–53.CrossRefGoogle Scholar
  60. Geldmacher DS, Provenzano G, McRae T, Mastey V, Ieni JR. Donepezil is associated with delayed nursing home placement in patients with Alzheimer’s disease. J Am Geriatr Soc. 2003;51:937–44.PubMedCrossRefGoogle Scholar
  61. Ghadiri-Sani M, Larner AJ. Cognitive screening instrument use in primary care: is it changing? Clin Pract. 2014;11:425–9.CrossRefGoogle Scholar
  62. Goldman JS, Farmer JM, Wood EM, et al. Comparison of family histories in FTLD subtypes and related tauopathies. Neurology. 2005;65:1817–9.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Hancock P, Larner AJ. Cambridge Behavioural Inventory for the diagnosis of dementia. Prog Neurol Psychiatry. 2008;12(7):23–5.CrossRefGoogle Scholar
  64. Hancock P, Larner AJ. Clinical utility of Patient Health Questionnaire-9 (PHQ-9) in memory clinics. Int J Psychiatry Clin Pract. 2009;13:188–91.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Hancock P, Larner AJ. Cornell Scale for Depression in Dementia: clinical utility in a memory clinic. Int J Psychiatry Clin Pract. 2015;19:71–4.PubMedCrossRefGoogle Scholar
  66. Heath Y. Evaluating the effect of therapeutic gardens. Am J Alzheimers Dis Other Demen. 2004;19:239–42.PubMedCrossRefGoogle Scholar
  67. Hogan DB, Ebly EM. Complementary medicine use in a dementia clinic population. Alzheimer Dis Assoc Disord. 1996;10:63–7.PubMedCrossRefGoogle Scholar
  68. Holmes C, Lovestone S. Long-term cognitive and functional decline in late onset Alzheimer’s disease: therapeutic implications. Age Ageing. 2003;32:200–4.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med. 2012;336:893–903.CrossRefGoogle Scholar
  70. Jackson D, Roberts G, Wu ML, Ford R, Doyle C. A systematic review of the effect of telephone, internet or combined support for carers of people living with Alzheimer’s, vascular or mixed dementia in the community. Arch Gerontol Geriatr. 2016;66:218–36.PubMedCrossRefGoogle Scholar
  71. Jorm AF, Rogers B, Christensen H. Use of medications to enhance memory in a large community sample of 60-64 year olds. Int Psychogeriatr. 2004;16:209–17.PubMedCrossRefGoogle Scholar
  72. Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt H-P, van den Bussche H. Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomised clinical trials. BMJ. 2005;331:321–3.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kertesz A, Morlog D, Light M, et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord. 2008;25:178–85.PubMedCrossRefGoogle Scholar
  74. Kitchiner D, Bundred P. Integrated care pathways. Arch Dis Child. 1996;75:166–8.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J. Risk score for the prediction of dementia in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol. 2006;5:735–41.PubMedCrossRefGoogle Scholar
  76. Knopman DS, Kitto J, Deinard S, Heiring J. Longitudinal study of death and institutionalization in patients with primary degenerative dementia. J Am Geriatr Soc. 1988;36:108–12.PubMedCrossRefGoogle Scholar
  77. Krupp LB, Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE. Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology. 2004;63:1579–85.PubMedCrossRefGoogle Scholar
  78. Kurlan R, editor. Handbook of secondary dementias. New York: Taylor and Francis; 2006.Google Scholar
  79. Kurrle S, Brodaty H, Hogarth R. Physical comorbidities of dementia. Cambridge: Cambridge University Press; 2012.CrossRefGoogle Scholar
  80. Lanctôt KL, Herrmann N, Yau KK, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ. 2003;169:557–64.PubMedPubMedCentralGoogle Scholar
  81. Larner AJ. Alzheimer’s disease: targets for drug development. Mini-Rev Med Chem. 2002;2(1):1–9.PubMedCrossRefGoogle Scholar
  82. Larner AJ. Use of the internet and of the NHS Direct telephone helpline for medical information by a cognitive function clinic population. Int J Geriatr Psychiatry. 2003;18:118–22.PubMedCrossRefGoogle Scholar
  83. Larner A. I think I need a psychiatrist. BMJ. 2003b;326:273.PubMedCentralCrossRefGoogle Scholar
  84. Larner AJ. Cholinesterase inhibitor use at a cognitive function clinic. Prog Neurol Psychiatry. 2004a;8(4):14, 18, 20.Google Scholar
  85. Larner AJ. Secretases as therapeutic targets in Alzheimer’s disease: patents 2000-2004. Exp Opin Ther Patents. 2004b;14:1403–20.CrossRefGoogle Scholar
  86. Larner AJ. Gardening and dementia. Int J Geriatr Psychiatry. 2005a;20:796–7.PubMedCrossRefGoogle Scholar
  87. Larner AJ. Two simple questions in the identification of dementia. J Neurol Neurosurg Psychiatry 2005b;76:1317 (abstract 023).Google Scholar
  88. Larner AJ. Searching the internet for medical information: frequency over time and by age and gender in an outpatient population in the UK. J Telemed Telecare. 2006a;12:186–8.PubMedCrossRefGoogle Scholar
  89. Larner AJ. Medical hazards of the internet: gambling in Parkinson’s disease. Mov Disord. 2006b;21:1789.PubMedCrossRefGoogle Scholar
  90. Larner AJ. Headache related to use of cholinesterase inhibitors: study of a Cognitive Function Clinic population. J Headache Pain. 2006;7:440–1.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Larner AJ. Neurological signs of aging. In: Pathy MSJ, Sinclair AJ, Morley JE, editors. Principles and practice of geriatric medicine. 4th ed. Chichester: Wiley; 2006d. p. 743–50.Google Scholar
  92. Larner AJ. Alzheimer 100. Adv Clin Neurosci Rehabil. 2006e;6(5):24.Google Scholar
  93. Larner AJ. Awareness and use of complementary therapies for AD. Prog Neurol Psychiatry. 2007a;11(8):27,29.CrossRefGoogle Scholar
  94. Larner AJ. Do cholinesterase inhibitors alter the course of dementia? Prog Neurol Psychiatry. 2007b;11(5):26–8.CrossRefGoogle Scholar
  95. Larner AJ. Neurologists still have a role in the dementia care pathway. Clin Med. 2007c;7:528–9.CrossRefGoogle Scholar
  96. Larner AJ. Antisocial behaviour and neuroacanthocytosis. A reply. Int J Clin Pract. 2007d;61:1419.CrossRefGoogle Scholar
  97. Larner AJ. Integrated care pathways in dementia: a challenge to National Institute for Health and Clinical Excellence/Social Care Institute for Excellence guidance. J Integr Care Pathways. 2007e;11:95–9.CrossRefGoogle Scholar
  98. Larner AJ. Idiopathic intracranial hypertension: towards an integrated care pathway. J Integr Care Pathways. 2007f;11:62–5.CrossRefGoogle Scholar
  99. Larner AJ. Neuropsychological neurology: the neurocognitive impairments of neurological disorders. Cambridge: Cambridge University Press; 2008a.CrossRefGoogle Scholar
  100. Larner AJ. Delusion of pregnancy in frontotemporal lobar degeneration with motor neurone disease (FTLD/MND). Behav Neurol. 2008b;19:199–200.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Larner AJ. Commentary on Living Well with Dementia: A National Dementia Strategy. Adv Clin Neurosci Rehabil. 2009a;9(1):27–8.Google Scholar
  102. Larner AJ. Impact of the National Institute for Health and Clinical Excellence and Social Care Institute for Excellence’s dementia guidelines in a neurology-led memory clinic. Clin Med. 2009b;9:197–8.CrossRefGoogle Scholar
  103. Larner AJ. Transdermal rivastigmine for Alzheimer’s disease: skin deep or scratching the surface? Int J Clin Pract. 2010a;64:534–6.PubMedCrossRefGoogle Scholar
  104. Larner AJ. Cholinesterase inhibitors—beyond Alzheimer’s disease. Exp Rev Neurotherapeutics. 2010b;10:1699–705.CrossRefGoogle Scholar
  105. Larner AJ. Cognitive impairment: update on current treatments and future prospects. In: Macallister R, editor. Horizons in Medicine 22. The proceedings of the Advanced Medicine Conference, vol. 2010. London: Royal College of Physicians; 2010c. p. 35–41.Google Scholar
  106. Larner AJ. Impact of the National Dementia Strategy in a neurology-led memory clinic. Clin Med. 2010d;10:526.CrossRefGoogle Scholar
  107. Larner AJ. Co-occurrence of bipolar disorder and cluster headache. Prog Neurol Psychiatry. 2010e;14(6):9–10.Google Scholar
  108. Larner AJ. Teleneurology by internet and telephone. A study in self-help. London: Springer; 2011a.CrossRefGoogle Scholar
  109. Larner AJ. Telemedicine and older people. GM Geriatr Med. 2011b;41:247–50,52.Google Scholar
  110. Larner AJ. Telemedicine and older neurology outpatients: use of NHS Direct and of the Internet in the UK. Can Geriatr J. 2011c;14:104–7.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Larner AJ. Impact of the 2011 NICE guidance on dementia drugs in a neurology-led memory clinic. Clin Med. 2012a;12:496.CrossRefGoogle Scholar
  112. Larner AJ. Neurological signs of aging. In: Sinclair A, Morley JE, Vellas B, editors. Pathy’s principles and practice of geriatric medicine. 5th ed. Chichester: Wiley; 2012b. p. 609–16.Google Scholar
  113. Larner AJ. Neuropsychological neurology: the neurocognitive impairments of neurological disorders (2nd edition). Cambridge: Cambridge University Press; 2013a.CrossRefGoogle Scholar
  114. Larner AJ. Delusion of pregnancy: a case revisited. Behav Neurol. 2013b;27:293–4.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Larner AJ. Impact of the National Dementia Strategy in a neurology-led memory clinic: 5-year data. Clin Med. 2014;14:216.CrossRefGoogle Scholar
  116. Larner AJ. Invited opinion piece: NICE guidelines on delaying and preventing dementia in later life. Adv Clin Neurosci Rehabil. 2015a;15(5):20.Google Scholar
  117. Larner AJ. Diagnostic test accuracy studies in dementia: a pragmatic approach. London: Springer; 2015b.CrossRefGoogle Scholar
  118. Larner AJ. A dictionary of neurological signs. 4th ed. London: Springer; 2016.CrossRefGoogle Scholar
  119. Larner AJ. Dementia and the health of the nation. In: Severn A, editor. Cognitive changes after surgery. London: Springer; 2018a (in press).Google Scholar
  120. Larner AJ. Metamemory: a construct with diagnostic utility in a cognitive disorders clinic? Int J Geriatr Psychiatry. 2018b;33:553–4.PubMedCrossRefGoogle Scholar
  121. Larner AJ, Bracewell RM. Predicting Alzheimer’s disease: a polygenic hazard score. J R Coll Physicians Edinb. 2017;47:151–2.PubMedCrossRefGoogle Scholar
  122. Larner AJ, Doran M. Broader assessment needed for treatment decisions in AD. Prog Neurol Psychiatry. 2002;6(3):5–6.Google Scholar
  123. Larner AJ, Doran M. Prion diseases: update on therapeutic patents, 1999-2002. Exp Opin Ther Patents. 2003;13:67–78.CrossRefGoogle Scholar
  124. Larner A, Storton K. Clinical review: Alzheimer’s disease. GP. 2011;28 January:32–4.Google Scholar
  125. Li Y, Hai S, Zhou Y, Dong BR. Cholinesterase inhibitors for rarer dementias associated with neurological conditions. Cochrane Database Syst Rev. 2015;(3):CD009444.Google Scholar
  126. Lincoln P, Fenton K, Alessi C, et al. The Blackfriars Consensus on brain health and dementia. Lancet. 2014;383:1805–6.PubMedCrossRefGoogle Scholar
  127. Lipton AM, Marshall CD. The common sense guide to dementia for clinicians and caregivers. New York: Springer; 2013.CrossRefGoogle Scholar
  128. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390:2673–734.PubMedCrossRefGoogle Scholar
  129. Lopez OL, Becker JT, Wisniewski S, Saxton J, Kaufer DI, DeKosky ST. Cholinesterase inhibitor treatment alters the natural history of Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2002;72:310–4.PubMedPubMedCentralCrossRefGoogle Scholar
  130. Lopez OL, Becker JT, Saxton J, Sweet RA, Klunk W, DeKosky ST. Alteration of a clinically meaningful outcome in the natural history of Alzheimer’s disease by cholinesterase inhibition. J Am Geriatr Soc. 2005;53:83–7.PubMedCrossRefGoogle Scholar
  131. Lopez OL, Becker JT, Wahed AS, Saxton J, Sweet RA, Wolk DA, Klunk W, DeKosky ST. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry. 2009;80:600–7.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Lovera JF, Kim E, Heriza E, et al. Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial. Neurology. 2012;79:1278–84.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol. 2010;9:702–16.PubMedCrossRefGoogle Scholar
  134. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for the treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1000–15.PubMedPubMedCentralCrossRefGoogle Scholar
  135. Masoodi N. Review: cholinesterase inhibitors do not reduce progression to dementia from mild cognitive impairment. Ann Intern Med. 2013;158:JC2–3.CrossRefGoogle Scholar
  136. Matthews FE, Stephan BC, Robinson L, et al. A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II. Nat Commun. 2016;7:11398.PubMedPubMedCentralCrossRefGoogle Scholar
  137. McKee M, Karanikolos M, Belcher P, Stuckler D. Austerity: a failed experiment on the people of Europe. Clin Med. 2012;12:346–50.CrossRefGoogle Scholar
  138. McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000;356:2031–6.PubMedCrossRefGoogle Scholar
  139. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;(2):CD003154.Google Scholar
  140. Mendez MF, Lauterbach EC, Sampson SM, ANPA Committee on Research. An evidence-based review of the psychopathology of frontotemporal dementia: a report of the ANPA Committee on Research. J Neuropsychiatry Clin Neurosci. 2008a;20:130–49.PubMedCrossRefGoogle Scholar
  141. Mendez MF, Shapira JS, Woods RJ, Licht EA, Saul RE. Psychotic symptoms in frontotemporal dementia: prevalence and review. Dement Geriatr Cogn Disord. 2008b;25:206–11.PubMedCrossRefGoogle Scholar
  142. Menon R, Larner AJ. Use of cognitive screening instruments in primary care: the impact of national dementia directives (NICE/SCIE, National Dementia Strategy). Fam Pract. 2011;28:272–6.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Naidoo M, Bullock R. An integrated care pathway for dementia. Best practice for dementia care. London: Mosby International; 2001.Google Scholar
  144. National Audit Office. Improving services and support for people with dementia. London: National Audit Office; 2007.Google Scholar
  145. National Audit Office. Improving dementia services in England—an interim report. ( London: National Audit Office; 2010.Google Scholar
  146. National Institute for Clinical Excellence. Guidance on the use of donepezil, rivastigmine, and galantamine for the treatment of Alzheimer’s disease (Technology Appraisal Guidance No. 19). London: NICE; 2001.Google Scholar
  147. National Institute for Health and Care Excellence. Dementia, disability and frailty in later life—mid-life approaches to delay or prevent onset. NICE guidelines. London: NICE (; 2015.Google Scholar
  148. National Institute for Health and Clinical Excellence. Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer’s disease. Includes a review of NICE technology appraisal guidance 19. Nice technology appraisal guidance 111. London: NICE; 2006.Google Scholar
  149. National Institute for Health and Clinical Excellence. Final appraisal determination: donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease (review of NICE technology appraisal guidance 111). Technology appraisal 217. London: NICE; 2011.Google Scholar
  150. National Institute for Health and Clinical Excellence/Social Care Institute for Excellence. Dementia: supporting people with dementia and their carers in health and social care. NICE Clinical Guidance 42. London: National Institute for Health and Clinical Excellence (; 2006.Google Scholar
  151. Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385:2255–63.PubMedCrossRefGoogle Scholar
  152. Oken BS, Storzbach DM, Kaye JA. The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol. 1998;55:1409–15.PubMedCrossRefGoogle Scholar
  153. Panicker J, Larner AJ. Two-week wait referrals for CNS cancer—are they working? J Neurol Neurosurg Psychiatry. 2012;83(Suppl2):A30–1.Google Scholar
  154. Patterson C, Feightner JW, Garcia A, Hsiung GY, MacKnight C, Sadovnick AD. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ. 2008;178:548–56.PubMedPubMedCentralCrossRefGoogle Scholar
  155. Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379–88.PubMedPubMedCentralCrossRefGoogle Scholar
  156. Prince M, Wimo A, Guerchet M, et al. World Alzheimer Report 2015. The global impact of dementia. An analysis of prevalence, incidence, cost and trends. London: Alzheimer’s Disease International; 2015.Google Scholar
  157. Provenzano G, Duttagupta S, McRae T, Mastey V, Ellis B, Ieni J. Delays in nursing home placement for patients with Alzheimer’s disease associated with treatment with donepezil may have health care cost-saving implications. Value Health 2001;4:158 (abstract).Google Scholar
  158. Rabins PV, Lyketsos CG, Steele CD. Practical dementia care. 3rd ed. New York: Oxford University Press; 2016.Google Scholar
  159. Rafii MS, Aisen PS. Advances in Alzheimer’s disease drug development. BMC Med. 2015;13:62.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148:379–97.PubMedCrossRefGoogle Scholar
  161. Randall A, Ellis R, Hywel B, Davies RR, Alusi SH, Larner AJ. Rapid cognitive decline: not always Creutzfeldt-Jakob disease. J R Coll Phys Edinb. 2015;45:209–12.CrossRefGoogle Scholar
  162. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.PubMedPubMedCentralCrossRefGoogle Scholar
  163. Ritchie CW, Ames D, Clayton T, Lai R. Metaanalysis of randomized trials of the efficacy and safety of donepezil, galantamine and rivastigmine for the treatment of Alzheimer disease. Am J Geriatr Psychiatry. 2004;12:358–69.PubMedCrossRefGoogle Scholar
  164. Rodda J, Carter J. Cholinesterase inhibitors and memantine for symptomatic treatment of dementia. BMJ. 2012;344:e2986.PubMedCrossRefGoogle Scholar
  165. Rolinski M, Fox C, Maidment I, McShane R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson’s disease dementia and cognitive impairment in Parkinson’s disease. Cochrane Database Syst Rev. 2012;(3):CD006504.Google Scholar
  166. Rosness TA, Haugen PK, Passant U, Engedal K. Frontotemporal dementia – a clinically complex diagnosis. Int J Geriatr Psychiatry. 2008;23:837–42.PubMedCrossRefGoogle Scholar
  167. Royal College of Psychiatrists/Alzheimer’s Society. Services for younger people with Alzheimer’s disease and other dementias. London: Royal College of Psychiatrists/Alzheimer’s Society; 2006.Google Scholar
  168. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev. 2012;(9):CD009132.Google Scholar
  169. Sabia S, Dugravot A, Dartigues JF, et al. Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study. BMJ. 2017;357:j2709.PubMedPubMedCentralCrossRefGoogle Scholar
  170. Salloway S, Ferris S, Kluger A, et al. Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial. Neurology. 2004;63:651–7.PubMedCrossRefGoogle Scholar
  171. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med. 1997;336:1216–22.PubMedCrossRefGoogle Scholar
  172. Sathasivam S, Doran M, Larner AJ. Frontotemporal lobar degeneration with motor neurone disease (FTLD/MND): presentations in psychiatric practice. Int J Psychiatry Clin Pract. 2008;12:138–41.PubMedCrossRefGoogle Scholar
  173. Scharre DW, editor. Long-term management of dementia. Abingdon: Informa; 2010.Google Scholar
  174. Sharma P, Herrmann N, Rochon PA, et al. Perceptions of natural health products among patients attending a memory clinic. Am J Alzheimers Dis Other Demen. 2006;21:156–63.PubMedCrossRefGoogle Scholar
  175. Storton K, Davies M, Cagliarini AM, Larner AJ. Frontotemporal dementia: supportive role of the Alzheimer’s Society. Dement Geriatr Cogn Disord. 2012;34(Suppl1):113.Google Scholar
  176. Swash M, Brooks DN, Day NE, Frith CD, Levy R, Warlow CP. Clinical trials in Alzheimer’s disease. A report from the Medical Research Council Alzheimer’s Disease Clinical Trials Committee. J Neurol Neurosurg Psychiatry. 1991;54:178–81.PubMedPubMedCentralCrossRefGoogle Scholar
  177. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291:317–24.PubMedCrossRefGoogle Scholar
  178. Thompson PA, Wright DE, Counsell CE, Zajicek J. Statistical analysis, trial design and duration in Alzheimer’s disease clinical trials: a review. Int Psychogeriatr. 2012;24:689–97.PubMedCrossRefGoogle Scholar
  179. Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357:j2353.PubMedPubMedCentralCrossRefGoogle Scholar
  180. Trevitt CR, Collinge J. A systematic review of prion therapeutics in experimental models. Brain. 2006;129:2241–65.PubMedCrossRefGoogle Scholar
  181. van de Glind EM, van Enst WA, van Munster BC, et al. Pharmacological treatment of dementia: a scoping review of systematic reviews. Dement Geriatr Cogn Disord. 2013;36:211–28.PubMedCrossRefGoogle Scholar
  182. Varma AR, Snowden JS, Lloyd JJ, et al. Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer’s disease and frontotemporal dementia. J Neurol Neurosurg Psychiatry. 1999;66:184–8.PubMedPubMedCentralCrossRefGoogle Scholar
  183. Vellas B, Coley N, Ousset PJ, et al. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol. 2012;11:851–9.PubMedCrossRefGoogle Scholar
  184. Whitehead A, Perdomo C, Pratt RD, Birks J, Wilcock GK, Evans JG. Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer’s disease: a meta-analysis of individual patient data from randomised controlled trials. Int J Geriatr Psychiatry. 2004;19:624–33.PubMedCrossRefGoogle Scholar
  185. Wilcock G, Howe I, Coles H, Lilienfeld S, Truyen L, Zhu Y, Bullock R, Members of the GAL-GBR2 Study Group. A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease. Drugs Aging. 2003;20:777–89.PubMedCrossRefGoogle Scholar
  186. Wilcock GK, Black SE, Hendrix SB, Zavitz KH, Swabb EA, Laughlin MA, Tarenflurbil Phase II Study Investigators. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: a randomised phase II trial. Lancet Neurol. 2008;7:483–93. [Erratum Lancet Neurol. 2008;7:575].PubMedCrossRefGoogle Scholar
  187. Williamson J, Larner AJ. Young-onset cognitive decline: not always variant Creutzfeldt-Jakob disease. Eur J Neurol. 2016;23(Suppl1):368. (abstract P21049).Google Scholar
  188. Winblad B, Cummings J, Andreasen N, et al. A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s disease—rivastigmine patch versus capsule. Int J Geriatr Psychiatry. 2007;22:456–67.PubMedCrossRefGoogle Scholar
  189. Winblad B, Gauthier S, Scinto L, et al. Safety and efficacy of galantamine in subjects with mild cognitive impairment. Neurology. 2008;70:2024–35.PubMedCrossRefGoogle Scholar
  190. Wong SH, Steiger MJ, Larner AJ, Fletcher NA. Hereditary myoclonus dystonia (DYT11): a novel SGCE mutation with intrafamilial phenotypic heterogeneity. Mov Disord. 2010;15:956–7.CrossRefGoogle Scholar
  191. Wu YT, Fratiglioni L, Matthews FE, et al. Dementia in western Europe: epidemiological evidence and implications for policy making. Lancet Neurol. 2016;15:116–24.PubMedCrossRefGoogle Scholar
  192. Zerr I, Kallenberg K, Summers DM, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain. 2009;132:2659–68. [Erratum Brain. 2012;135:1335].PubMedPubMedCentralCrossRefGoogle Scholar
  193. Ziso B, Marsden D, Alusi S, Larner AJ. “Undifferentiated schizophrenia” revisited. J Neuropsychiatry Clin Neurosci. 2014;26:E62–3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • A. J. Larner
    • 1
  1. 1.Cognitive Function ClinicWalton Centre for Neurology and NeurosurgeryLiverpoolUK

Personalised recommendations