In Pursuit of Memory
Page 25
As a child, I had viewed Abbas’s illness as something to fear and something to accept. Alzheimer’s was an invisible and terrifying cross to bear, a profound loss that my generation would not see an end to. Now, I understood just how innocent that thinking was. In writing this book I had discovered an astonishingly intricate yet eminently malleable disease. I had witnessed extraordinary minds catapulting neuroscience into unimaginable futures. And I had seen breathtaking acts of human courage and unalloyed sacrifice. We are closer than ever to the abolition of Alzheimer’s.
It truly is the beginning of the end.
Acknowledgements
THIS BOOK WAS made possible, first and foremost, by the patients and patient relatives who agreed to be interviewed. I am deeply grateful for their sincerity, openness and astonishing courage. For reasons of anonymity, I shall only cite those who agreed to share their real names; to all the people behind the pseudonyms, I offer you my heartfelt gratitude. I am also enormously thankful to the scientists and physicians for sharing their knowledge and intuition. Their remarkable ability to clarify complex topics provided the animating spirit for my writing, and I hope I have done their work justice.
I’m thankful to Gabriel Aristizábal, Kaj Blennow, Hari Chand, John Collinge, Paige Cramer, Sebastian Crutch, Jeffrey Cummings, Ricardo Dolmetsch, Matteo Farinella, Jens Foell, Nick Fox, Mary Ganguli, Alison Goate, Lawrence Goldstein, John Hardy, Martin Huntley, Victoria Huntley, Sarah Jarvis, Carol Jennings, John Jennings, Stuart Jennings, Mathias Jucker, Sasha Kamb, Ryuta Kawashima, William Klunk, Vijay Kumar, Michael Landon, Gary Landreth, Patrick Lewis, Francisco Lopera, Simon Lovestone, Lucía Madrigal, Karen Magorrian, George Martin, Chester Mathis, Marika Mattsson, Jeremy Mills, Pradeep Narayan, Karoly Nikolich, Thomas Piers, Jeremy Reed, Cressida Robson, Allen Roses, Maria Alejandra Ruiz, Natalie Ryan, Ian Sample, Dale Schenk, Kari Stefánsson, William Summers, Naji Tabet, Rudolph Tanzi, Selina Wray and Henrik Zetterberg.
A special thanks to Carrie Plitt, my exceedingly talented agent at Conville and Walsh, whose comments and revisions made this book significantly better. Additionally, this book could not have been published without the exceptional support of the teams at John Murray and Little, Brown. My wonderful editors, Kate Craigie and Georgina Laycock, provided countless insights in shaping this book.
I owe a huge thanks to Hajra Siraj, my most loyal reader. Her wisdom, guidance and unrivalled compassion helped me on this journey in innumerable ways. Finally, I am for ever indebted to my parents. They sacrificed so much for my education, and taught me at a young age that the purpose of life is to help others.
Resources
The idea is to die young as late as possible.
Ashley Montagu, attributed
WHAT CAN WE do? This is hard to answer, but not impossible. There is advice worth heeding, based on the clinical experience of doctors and nurses. First: early diagnosis is critical. If you are having memory problems that worry you, problems that feel like more than normal ageing, you must book an appointment to see your doctor. It truly is a case of the earlier, the better: our methods of detection are rapidly advancing. And while it can be difficult advising someone to seek medical attention for a mental health problem (again I speak from experience: persuading my mother to see a doctor about anything is like trying to persuade Kim Jong-un to see a therapist), we must remind people that it is a serious disease.
Second, but no less important: remain active and social for as long as possible. Having family and friends around can have an immensely positive effect on a patient’s mood and sense of well-being. In her instructive book Dementia: The One-Stop Guide, dementia nurse June Andrews suggests that families should also ‘start a private blog, where everyone has their own responsibility to log in and find out for themselves what is going on’, and points out that ‘friends are not a luxury; they are a necessity for maintaining your health and sanity’. Keeping diaries and calendars and notes will also help manage symptoms. So too, perhaps, will eating well, drinking less alcohol, exercising more, and staying mentally active. A healthy lifestyle might not prevent Alzheimer’s, but it may slow it down. On a lighter note, stay positive. Patients often want to keep a sense of humour about what’s happening to them, which was certainly true with many of the patients I met.
I am fully persuaded that we will defeat Alzheimer’s in our lifetime. In the meantime, perhaps the best advice I can give is to keep looking to the future like the people in this book are–with high spirits, fiery determination and irrepressible optimism.
Some of the best organisations for families, carers and patients:
Age UK
Tel: 0800 678 1174
Email: contact@ageuk.org.uk
Website: www.ageuk.org.uk
Alzheimer’s Association
Tel: +1 800 272 3900
Email: info@alz.org
Website: www.alz.org
Alzheimer’s Disease Education and Referral Center
Tel: +1 800 438 4380
Email: adear@nia.nih.gov
Website: www.nia.nih.gov/alzheimers
Alzheimer’s Disease International
Tel: +44 20 7981 0880
Email: info@alz.co.uk
Website: www.alz.co.uk
Alzheimer’s Europe
Tel: +352 29 79 70
Email: info@alzheimer-europe.org
Website: www.alzheimer-europe.org
Alzheimer’s Foundation of America
Tel: +1 866 232 8484
Email: info@alzfdn.org
Website: www.alzfdn.org
Alzheimer’s Research Forum
Email: contact@alzforum.org
Website: www.alzforum.org
Alzheimer’s Research UK
Tel: 0300 111 5555
Email: enquiries@alzheimersresearchuk.org
Website: www.alzheimersresearchuk.org
Alzheimer’s Society
Tel: 0300 222 1122
Email: enquiries@alzheimers.org.uk
Website: www.alzheimers.org.uk
Caregiver Action Network
Tel: +1 202 454 3970
Email: info@caregiveraction.org
Website: www.caregiveraction.org
Caregiver.com
Tel: +1 800 829 2734
Email: info@caregiver.com
Website: www.caregiver.com
Carers UK
Tel: 020 7378 4999
Email: info@carersuk.org
Website: www.carersuk.org
Dementia UK
Tel: 0800 888 6678
Email: info@dementiauk.org
Website: www.dementiauk.org
Family Caregiver Alliance
Tel: +1 415 434 3388
Email: info@caregiver.org
Website: www.caregiver.org
National Council for Palliative Care (NCPC)
Tel: 020 7697 1520
Website: www.ncpc.org.uk
NHS Choices
Website: www.nhs.uk
Office of the Public Guardian
Tel: 0870 739 5780
Email: customerservices@publicguardian.gsi.gov.uk
Website: www.gov.uk/government/organisations/office-of-the-public-guardian
Society for Neuroscience
Tel: +1 202 962 4000
Website: www.sfn.org
Notes
Preface: ‘A Peculiar Disease’
1. Prince, Comas-Herrera, et al., ‘World Alzheimer’s Report 2016’.
2. At the time of writing, Alzheimer’s overtook heart disease in England and Wales; it is now the leading cause of death. Office for National Statistics, Statistical Bulletin.
3. Reagan, Handwritten letter courtesy of the Ronald Reagan Presidential Foundation and Library.
4. Mukherjee, The Emperor of All Maladies, p.39.
5. Lambert, Ibrahim-Verbaas, et al., ‘Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease’.
6. Fraser, Consulting report, July 2015.
C
hapter 1: The Psychiatrist with a Microscope
1. World Health Organization (WHO), ‘Dementia: Fact Sheet’.
2. Deuteronomy 28:28.
3. Jameson, Essays on the Changes of the Human Body, at its Different Ages, p.138.
4. Cicero, How to Grow Old, p.77.
5. Galen, De symptomatum differentiis liber, in K. Kuhn, Opera omnia.
6. Boller, Handbook of Clinical Neurology (vol. 89), p.3.
7. Porter, Madness, p.42.
8. Hunt, The Story of Psychology, p.70.
9. Ibid., p.95.
10. Berrios, The History of Mental Symptoms, p.172.
11. Boller, Handbook of Clinical Neurology (vol. 89), p.4.
12. Bynum and Porter, Dictionary of Scientific Quotations, p.598.
13. Maurer and Maurer, Alzheimer, p.55.
14. Ibid., p.84.
15. Ibid., p.152.
16. Ibid., p.163.
Chapter 2: Understanding an Epidemic
1. Newton, ‘The identity of Alzheimer’s disease and senile dementia and their relationship to senility’.
2. Ballenger, Self, Senility, and Alzheimer’s Disease in Modern America, p.49.
3. K. B. R. Katzman, Alzheimer Disease, p.33.
4. Raine, ‘Correspondence: re: Robert Terry and Robert Katzman’.
5. Kidd, ‘Paired helical filaments in electron microscopy of Alzheimer’s disease’; Terry, Gonatas, Weiss, ‘Ultrastructural studies in Alzheimer’s presenile dementia’.
6. Ballenger, Self, Senility, and Alzheimer’s Disease in Modern America, p.81.
7. Roth, Tomlinson, Blessed, ‘Correlation between scores for dementia and counts of “senile plaques” in cerebral grey matter of elderly subjects’.
8. Wade, ‘Thomas S. Kuhn: Revolutionary Theorist of Science’.
9. R. Katzman, ‘Editorial: The prevalence and malignancy of Alzheimer’s disease’.
Chapter 3: A Medicine for Memory
1. Reagan, Proclamation 5565–National Alzheimer’s Disease Month.
2. Wolpert, Malignant Sadness, p.104.
3. This is a simplification, of course; there is a phenomenon called neuroplasticity that gives these units a degree of exchangeability. In fact neuroplasticity is why stroke victims can eventually regain certain functions, because the brain has literally rewired itself.
4. P. Davies and Maloney, ‘Selective loss of central cholinergic neurons in Alzheimer’s disease’.
5. Perry, Perry, et al., ‘Necropsy evidence of central cholinergic deficits in senile dementia’.
6. Bowen, Smith, et al., ‘Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies’.
7. B. Taylor, The Last Asylum, p.249.
8. Lømo, ‘The discovery of long-term potentiation’.
9. Drachman and Leavitt, ‘Human memory and the cholinergic system’.
10. Bartus, Dean, et al., ‘The cholinergic hypothesis of geriatric memory dysfunction’.
11. Summers, Viesselman, et al., ‘Use of THA in treatment of Alzheimer’s-like dementia’.
12. Summers, Majovski, et al., ‘Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer’s type’.
Chapter 4: Diagnosis
1. Prince, Wimo, et al., ‘World Alzheimer Report 2015’.
2. UK Department of Health, Dementia, p.6.
3. Prince, Bryce, Ferri, ‘The benefits of early diagnosis and intervention’.
Chapter 5: The Alzheimer’s Gene
1. Heston, Mastri, et al., ‘Dementia of the Alzheimer type’.
2. Tanzi, Decoding Darkness, p.21.
3. Glenner and Wong, ‘Alzheimer’s disease’.
4. Glenner and Wong, ‘Alzheimer’s disease and Down’s syndrome’.
5. Goldgaber, Lerman, et al., ‘Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease’; Tanzi, Gusella, et al., ‘Amyloid beta protein gene’; Robakis, Ramakrishna, et al., ‘Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides’; Kang, Lemaire, et al., ‘The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor’.
6. A. Goate, Chartier-Harlin, et al., ‘Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease’.
7. Popham, ‘Dementia: I have a 50:50 chance’.
Chapter 6: The Science Behind the Headlines
1. This data is for women. In men, heart disease remains the leading cause of death. It’s not clear why Alzheimer’s is more likely in women; some think it’s because women typically live longer, others think genetic differences are responsible.
2. J. A. Hardy and Higgins, ‘Alzheimer’s disease’.
3. Games, Adams, et al., ‘Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein’.
4. Duff and Hardy, ‘Mouse model made’.
5. Saunders, Strittmatter, et al., ‘Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease’.
6. Roses, ‘On the discovery of the genetic association of Apolipoprotein E genotypes and common late-onset Alzheimer disease’.
7. Strittmatter, Saunders, et al., ‘Apolipoprotein E’.
8. Small, Ercoli, et al., ‘Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease’.
9. Herrup, ‘The case for rejecting the amyloid cascade hypothesis’.
10. Correspondence with Professor Karoly Nikolich.
11. Shenk, The Forgetting, p.68.
Chapter 7: The Second Brain
1. Fields, The Other Brain, p.11.
2. McGeer, Itagaki, et al., ‘Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR’.
3. M. L. Block and Hong, ‘Microglia and inflammation-mediated neurodegeneration’; M. L. Block, Zecca, Hong, ‘Microglia-mediated neurotoxicity’.
4. Jebelli, Hooper, Pocock, ‘Microglial p53 activation is detrimental to neuronal synapses during activation-induced inflammation’; Jebelli, Su, et al., ‘Glia’; Jebelli, Hooper, Garden, Pocock, ‘Emerging roles of p53 in glial cell function in health and disease’.
5. Watkins and Treisman, ‘Cognitive impairment in patients with AIDS’.
6. Schenk, ‘Amyloid-β immunotherapy for Alzheimer’s disease’.
7. Only 18 per cent do, according to one estimate. Arrowsmith, ‘Trial watch’.
8. Hock, Konietzko, et al., ‘Antibodies against beta-amyloid slow cognitive decline in Alzheimer’s disease’.
9. Spinney, ‘The forgetting gene’.
10. Klunk, Engler, et al., ‘Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B’.
11. Stein, Four in America, p.175.
Chapter 8: Swedish Brain Power
1. Arai, Terajima, et al., ‘Tau in cerebrospinal fluid’; Blennow and Zetterberg, ‘The application of cerebrospinal fluid biomarkers in early diagnosis of Alzheimer disease’.
2. Shahim, Tegner, et al., ‘Blood biomarkers for brain injury in concussed professional ice hockey players’; Siman, Shahim, et al., ‘Serum SNTF increases in concussed professional ice hockey players and relates to the severity of postconcussion symptoms’.
3. Mapstone, Cheema, et al., ‘Plasma phospholipids identify antecedent memory impairment in older adults’.
4. Announced at the US Society for Neuroscience conference, Washington DC, November 2014.
5. Announced at the US Society for Neuroscience conference, San Diego CA, November 2013.
6. Clare Walton, of the Alzheimer’s Society, quoted in the Mail Online, 13 November 2013.
7. Global AgeWatch Index 2013: Insight report, summary and methodology.
8. Sontag, Illness as Metaphor, p.3.
Chapter 9: Stress
1. McEwen and Gianaros, ‘Stress-
and allostasis-induced brain plasticity’; Marcello, Gardoni, Di Luca, ‘Alzheimer’s disease and modern lifestyle’.
2. McEwen and Gianaros, ‘Central role of the brain in stress and adaptation’.
3. Ganzel, Kim, et al., ‘Resilience after 9/11’.
4. Yaffe, Vittinghoff, et al., ‘Post-traumatic stress disorder and risk of dementia among U.S. veterans’.
5. Csernansky, Dong, et al., ‘Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia’.
6. Wilson, Barnes, et al., ‘Proneness to psychological distress and risk of Alzheimer disease in a biracial community’.
7. Wilson, Arnold, et al., ‘Chronic psychological distress and risk of Alzheimer’s disease in old age’.
8. Baglietto-Vargas, Chen, et al., ‘Short-term modern life-like stress exacerbates Abeta-pathology and synapse loss in 3xTg-AD mice’.
9. Selye, The Stress of Life, p.247.
Chapter 10: Diet
1. M. C. Morris, Tangney, et al., ‘MIND diet associated with reduced incidence of Alzheimer’s disease’.