NOTES

Introduction

  1. The reality was: Yamamoto et al. (2015).

Chapter 1. The Long Game

  1. In 1900, life expectancy: Kinsella (1992).

  2. we have cut mortality rates by two-thirds in the industrialized world: Mensah et al. (2017).

  3. Death rates from cancer: Siegel et al. (2021).

Chapter 2. Medicine 3.0

  1. “First, do no harm”: Sokol (2013).

  2. as Steven Johnson points out: S. Johnson (2021).

  3. The Northwestern University economist: Gordon (2016).

  4. The study reported a 24 percent relative increase: Manson et al. (2013).

  5. The Titanic’s wireless operator: New York Times (1985).

Chapter 3. Objective, Strategy, Tactics

  1. “hallmarks of aging”: López-Otín et al. (2013).

  2. low LDL cholesterol does not cause cancer: Benn et al. (2011).

  3. higher LDL cholesterol is causally linked: Ference (2015).

Chapter 4. Centenarians

  1. “cigarettes, whiskey, and wild, wild women”: Taylor (2009).

  2. “I’ve only ever had one wrinkle”: Spencer (2005).

  3. Mildred Bowers: Picard (2018).

  4. centenarians are no more health-conscious: Rajpathak et al. (2011).

  5. according to the Census Bureau: United States Census Bureau (2022).

  6. Studies of Scandinavian twins: Hjelmborg et al. (2006).

  7. Being the sister of a centenarian: Sebastiani, Nussbaum, et al. (2016).

  8. The overall mortality rate for Americans: Xu (2016).

  9. According to research by Thomas Perls: Evert et al. (2003).

  10. “a double-edged sword”: Perls (2017).

  11. As Perls and his colleagues put it: Hitt et al. (1999).

  12. having one or two copies: Michaelson (2014).

  13. a large 2019 meta-analysis: Sebastiani, Gurinovich, et al. (2019).

  14. three SNPs (or variants) in FOXO3: Willcox et al. (2008).

  15. Since then, several other studies: Revelas et al. (2018).

  16. A genetic analysis of Spanish centenarians: Serna et al. (2012).

  17. For example, a 2007 study: Melov et al. (2007).

Chapter 5. Eat Less, Live Longer?

  1. Ultimately, he and others discovered: E.J. Brown et al. (1994); Sabatini et al. (1994).

  2. it is highly “conserved”: Tatebe and Shiozaki (2017).

  3. The job of mTOR: G.Y. Liu and Sabatini (2020).

  4. mTOR is like the general contractor”: Attia (2018a).

  5. “a finger in every major process”: Attia (2018a).

  6. “by postponing death from cancer”: D.E. Harrison, Strong, Sharp, et al. (2009).

  7. Even better, other labs: Selvarani, Mohammed, and Richardson (2021).

  8. the well-publicized finding: Baur et al. (2006).

  9. When resveratrol was subjected: Miller et al. (2011); Strong et al. (2013).

  10. nicotinamide riboside: D.E. Harrison, Strong, Reifsnyder, et al. (2021).

  11. rapamycin can extend mouse lifespans: Selvarani, Mohammed, and Richardson (2021).

  12. more modern experiments have demonstrated: Fontana and Partridge (2015).

  13. Studies dating back to the 1930s: McDonald and Ramsey (2010).

  14. when it senses low levels of nutrients: Hardie (2011).

  15. Autophagy is essential to life: Kourtis and Tavernarakis (2009).

  16. Mice who lack one specific autophagy gene: Karsli-Uzunbas et al. (2014).

  17. the rapamycin analog everolimus: Mannick et al. (2014).

  18. Kaeberlein is doing a large clinical trial: Creevy et al. (2022).

  19. actually seemed to improve cardiac function: Urfer et al. (2017).

  20. “One thing that’s been surprising to me”: Attia (2018b).

  21. One large 2014 analysis: Bannister et al. (2014).

Chapter 6. One Disease to Rule Them All

  1. His curiosity piqued, Zelman recruited: Zelman (1952).

  2. nonalcoholic steatohepatitis, or NASH: Ludwig et al. (1980).

  3. More than one in four people: S.A. Harrison et al. (2021).

  4. the average American adult male weighed: Fryar et al. (2018); Ogden et al. (2004).

  5. With regard to ALT liver values: Kwo, Cohen, and Lim (2017).

  6. Even that may not be low enough: Prati et al. (2002).

  7. by 2025, NASH and cirrhosis: Fayek et al. (2016).

  8. According to the Centers for Disease Control (CDC): CDC (2022b).

  9. If you meet three: Hirode and Wong (2020).

  10. About 90 percent of the US population: Araújo, Cai, and Stevens (2019).

  11. A large meta-analysis of studies: Stefan, Schick, and Häring (2017).

  12. when he surgically implanted fat tissue: Gavrilova et al. (2000).

  13. NAFLD is just one of many undesirable consequences: Tchernof and Després (2013).

  14. people of Asian descent: Anand et al. (2011); Sniderman, Bhopal, et al. (2007).

  15. research by Mitch Lazar: Ahima and Lazar (2013).

  16. This is where insulin resistance likely begins: M.C. Petersen and Shulman (2018).

  17. But insulin seems to be the most potent: Frayn (2019).

  18. the Greek physician Aretaeus of Cappadocia: Tuchman (2009).

  19. The composer Johann Sebastian Bach: Diamond (2003).

  20. the famed diabetologist Elliott Joslin: Joslin (1940).

  21. By 1970, around the time I was born: NIDDK (2018).

  22. according to a 2022 CDC report: CDC (2022e).

  23. In 2020: CDC (2020).

  24. deaths were attributed to type 2 diabetes: CDC (2020).

  25. we humans have a unique capacity: R.J. Johnson, Stenvinkel, et al. (2020).

  26. “We realized fructose was having effects”: Attia (2020c).

  27. Johnson and his team began investigating: R.J. Johnson and Andrews (2015).

  28. does not put the brakes on this ATP “spending”: R.J. Johnson, Sánchez-Lozada, et al. (2017).

  29. insulin resistance itself is associated with huge increases: Igwe et al. (2015); Matsuzaki et al. (2010); Zethelius and Cederholm (2015).

Chapter 7. The Ticker

  1. Globally, heart disease and stroke: Heron (2021); WHO (2019).

  2. estimated 2,300 people: CDC (2022c).

  3. It’s not just men who are at risk: ACS (2022a); Heron (2021).

  4. Fewer Sardinian men: Caselli and Lipsi (2006).

  5. Our vascular network is equally miraculous: Bautch and Caron (2015).

  6. The humble egg: McNamara (2015).

  7. Eating lots of saturated fat: Mensink and Katan (1992).

  8. most of the actual cholesterol that we consume: Lammert and Wang (2005).

  9. “There’s no connection whatsoever”: Jaret (1997).

  10. “cholesterol is not a nutrient of concern”: Dietary Guidelines Advisory Committee (2015).

  11. Fully half of all major adverse cardiovascular events: Sniderman, Thanassoulis, et al. (2016).

  12. Atlas of Atherosclerosis Progression and Regression: Stary (2003).

  13. Autopsy data from young people: Lawson (2016).

  14. Approximately 15 percent of people: Nasir et al. (2022); Uretsky et al. (2011).

  15. in JAMA Cardiology in 2021: Marston et al. (2022).

  16. 20 to 30 percent of the US population: Tsimikas et al. (2018).

  17. A class of drug called PCSK9: O’Donoghue et al. (2019).

  18. “Atherosclerosis probably would not occur: Libby (2021).

  19. there have been only thirteen reported cases: Orphanet (2022).

  20. Instead, we have over eighteen million cases: Ritchie and Roser (2018).

  21. scores of studies showing no ill effects: Dietschy, Turley, and Spady (1993); Ference et al. (2019); Forrester (2010); Jakubowski et al. (2021); Karagiannis et al. (2021); R. Le, Zhao, and Hegele (2022); Libby and Tokgözoğlu (2022); Masana et al. (2018); O’Keefe et al. (2004); Soran, Ho, and Durrington (2018); N. Wang et al. (2020).

  22. Does low HDL-C causally increase the risk: Haase et al. (2012).

  23. Does raising HDL-C causally lower the risk: Voight et al. (2012).

  24. deal-breaking side effects: du Souich, Roederer, and Dufour (2017); Stroes et al. (2015).

  25. statins are associated with a small increase: Mach et al. (2018); C.B. Newman et al. (2019).

  26. an asymptomatic rise in liver enzymes: Jose (2016).

  27. a 2018 JAMA Cardiology paper: Thanassoulis, Sniderman, and Pencina (2018).

Chapter 8. The Runaway Cell

  1. “This man had had a virulent and untreatable cancer”: Rosenberg and Barr (1992).

  2. ten-year survival rates nearly doubled: NCI (2022b).

  3. in 2017 there were more cancer deaths: NCI (2021).

  4. This year, if recent trends continue: NCI (2021).

  5. a gene called PTEN: Jamaspishvili et al. (2018).

  6. “These are the starting blocks”: Pollack (2005).

  7. only about 5 to 8 percent of US cancer research funding: Sleeman and Steeg (2010).

  8. the late author Christopher Hitchens: Hitchens (2014).

  9. two key hallmarks of cancer: Hanahan and Weinberg (2011).

  10. a German physiologist named Otto Warburg: Warburg (1924, 1956).

  11. the Warburg effect: Liberti and Locasale (2016).

  12. By the time he died in 1970: Christofferson (2017).

  13. Watson recounted: J.D. Watson (2009).

  14. Cantley, Matthew Vander Heiden, and Craig Thompson argued: Vander Heiden, Cantley, and Thompson (2009).

  15. Globally, about 12 to 13 percent: Avgerinos et al. (2019).

  16. Type 2 diabetes also: Lega et al. (2019).

  17. a family of enzymes called PI3-kinases: Bradley (2004); Fruman et al. (2017).

  18. one study of caloric restriction in humans: Mercken et al. (2013).

  19. The Emperor of All Maladies: Mukherjee (2011).

  20. Published in Nature in 2018: Hopkins et al. (2018).

  21. A randomized trial in 131 cancer patients: de Groot et al. (2020).

  22. using ice cream “as a topping on cake”: ACS (2022c).

  23. In 2010, Rosenberg and his team: Kochenderfer et al. (2010).

  24. The New England Journal of Medicine had recently reported: D.T. Le et al. (2015).

  25. an analysis by oncologists: Gay and Prasad (2017).

  26. One recent paper: Cavazzoni et al. (2020).

  27. immune system can recognize: Attia (2021b); Rosenberg (2021).

  28. Between 80 and 90 percent: Atkins et al. (2000).

  29. and 67 percent of: Taieb et al. (2020).

  30. 93 percent chance: Waks et al. (2019).

  31. About 70 percent of people: Hofseth et al. (2020).

  32. In 2020, some 3,640 Americans died: ACS (2022b).

  33. Galleri has been validated: X. Chen et al. (2021).

Chapter 9. Chasing Memory

  1. the e2 version of APOE: Reiman, Arboleda-Velasquez, et al. (2020).

  2. a certain variant of the gene Klotho: Belloy et al. (2020).

  3. Luckily, these mutations are very rare: Cacace, Sleegers, and Van Broeckhoven (2016); Cruchaga et al. (2012); Cuyvers and Sleegers (2016).

  4. Every single one of them failed: Cummings et al. (2022).

  5. “Amyloid and tau define the disease”: Kolata (2020).

  6. “plaque formation and other changes”: Blessed, Tomlinson, and Roth (1968).

  7. Researchers from the Memory and Aging Center: Rabinovici et al. (2019).

  8. A 2013 analysis of preserved tissue: Müller, Winter, and Graeber (2013).

  9. Lewy body dementia as well as: Kaivola et al. (2022).

  10. “She was expecting Oliver Sacks”: Attia (2018c).

  11. “Currently, firm conclusions cannot be drawn”: Daviglus et al. (2010).

  12. A two-year randomized controlled trial: Ngandu et al. (2015).

  13. Two other large European: Rosenberg et al. (2020); Andrieu et al. (2017); van Charante et al. (2016).

  14. a rapid drop in estradiol in women: Mosconi et al. (2018); Rahman et al. (2020); Ratnakumar et al. (2019); Zhou et al. (2020).

  15. new research suggests that women: Yan et al. (2022).

  16. Yet Parkinson’s also appears: Cerri et al. (2019).

  17. dementia has an extremely long prologue: Langa and Levine (2014).

  18. over forty-six million people: Brookmeyer et al. (2018).

  19. according to Francisco Gonzalez-Lima: Attia (2019).

  20. also known as “healthy user bias”: Yasuno et al. (2020).

  21. In their seminal 1968 paper: Blessed, Tomlinson, and Roth (1968).

  22. The brain is a greedy organ: Raichle and Gusnard (2002).

  23. His “barf bag theory”: de la Torre (2016).

  24. “We believed, and still do”: de la Torre (2018).

  25. vascular dementia is currently considered distinct: Wolters and Ikram (2019).

  26. Having type 2 diabetes doubles or triples your risk: Cholerton et al. (2016).

  27. insulin resistance alone is enough: Neth and Craft (2017).

  28. spraying insulin right into subjects’ noses: Freiherr et al. (2013).

  29. One study found that intranasal insulin: Chapman et al. (2018).

  30. The signal event here: Kerrouche et al. (2006).

  31. Brain imaging studies reveal: Reiman, Caselli, et al. (1996); Small et al. (2000); Sperling et al. (2011).

  32. Intriguingly, this reduction appears: Kerrouche et al. (2006).

  33. A woman with one copy: Neu et al. (2017).

  34. There is also some evidence: Montagne et al. (2020).

  35. It was the original human allele: Trumble and Finch (2019).

  36. children carrying APOE e4: Mitter et al. (2012); Oriá et al. (2007).

  37. higher levels of neuroinflammation in e4 carriers: Kloske and Wilcock (2020).

  38. DHA, found in fish oil: Yassine et al. (2017).

  39. ketogenic therapies improved general cognition: Grammatikopoulou et al. (2020).

  40. heavier drinking is itself a risk factor: Slayday et al. (2021).

  41. stress and anxiety-related risk: Maeng and Milad (2015).

  42. grip strength, an excellent proxy: Esteban-Cornejo et al. (2022).

  43. Sleep disruptions and poor sleep are potential drivers: C. Wang and Holtzman (2020).

  44. Studies have found that hearing loss: Zheng et al. (2017).

  45. P. gingivalis has also shown up: Dominy et al. (2019).

  46. reduce the risk of Alzheimer’s by about 65 percent: Laukkanen et al. (2017).

  47. and the risk of ASCVD by 50 percent: Laukkanen et al. (2015).

  48. lowering homocysteine with B vitamins: A. Smith et al. (2010).

  49. while optimizing omega-3 fatty acids: Oulhaj et al. (2016).

  50. Higher vitamin D levels: Maddock et al. (2015).

Chapter 10. Thinking Tactically

  1. “Cancer, like insanity”: Proctor (1995).

  2. one person every twelve minutes: NHTSA (2022a).

  3. a very high proportion of fatalities occur at intersections: NHTSA (2022b); Attia (2020b).

Chapter 11. Exercise

  1. 77 percent of the US population is like you: Blackwell and Clarke (2018).

  2. Going from zero weekly exercise: Wen et al. (2011).

  3. regular exercisers live as much as a decade longer: Reimers, Knapp, and Reimers (2012).

  4. habitual runners and cyclists: Booth and Zwetsloot (2010).

  5. The benefits of exercise begin: I.-M. Lee and Buchner (2008).

  6. The US government’s physical activity guidelines: HHS (2018).

  7. the single most powerful marker: Mandsager et al. (2018).

  8. A 2018 study in JAMA: Mandsager et al. (2018).

  9. greater relative risk of death than smoking: Mandsager et al. (2018).

  10. Someone in the bottom quartile of VO2 max: Mandsager et al. (2018).

  11. a much larger and more recent study: Kokkinos et al. (2022).

  12. “Cardiorespiratory fitness is inversely associated”: Mandsager et al. (2018).

  13. A ten-year observational study: Li et al. (2018).

  14. at least one study suggests: Artero et al. (2011).

  15. side-by-side comparison of exercise studies versus drug studies: Naci and Ioannidis (2015).

  16. Endurance exercise such as running or cycling: Seifert et al. (2010).

  17. Exercise helps keep the brain vasculature healthy: Barnes and Corkery (2018).

  18. Longitudinal and cross-sectional studies: Westerterp et al. (2021).

  19. One Chilean study: Bunout et al. (2011).

  20. Having more muscle mass on your exoskeleton: Jones et al. (2017).

  21. correlated with a lower risk of falling: Van Ancum et al. (2018).

  22. Eight hundred thousand older people are hospitalized: CDC (2021).

  23. muscle atrophy and sarcopenia: H.-S. Lin et al. (2016).

  24. A recent study of older British adults: Veronese et al. (2022).

  25. subjects who are obese: Nicklas et al. (2015).

  26. or recovering from cancer treatment: K.L. Campbell et al. (2019).

  27. even those who are already elderly and frail: Zhang et al. (2020).

  28. your muscle strength will decline: Danneskiold-Samsøe et al. (2009); Hughes et al. (2001); Lindle et al. (1997).

Chapter 12. Training 101

  1. Zone 2 is one of five levels of intensity: Allen and Coggan (2010).

  2. a fascinating study: San-Millán and Brooks (2018).

  3. a process called mitochondrial biogenesis: Lemasters (2005).

  4. why zone 2 is such a powerful mediator: Kawada and Ishii (2005).

  5. glucose uptake increases as much as one-hundred-fold: Richter (2021).

  6. exercise also activates other pathways: McMillin et al. (2017).

  7. a side benefit of zone 2: Seifert et al. (2010).

  8. this measure of peak aerobic capacity: Mandsager et al. (2018).

  9. Studies suggest that your VO2 max will decline: C.-H. Kim et al. (2016).

  10. it begins to threaten your ability: Shephard (2009).

  11. well-trained octogenarian endurance athletes: Trappe et al. (2013).

  12. increasing your VO2 max: Shephard (2009).

  13. One study found that: Shephard et al. (2009).

  14. fitness of someone decades younger than you: Booth and Zwetsloot (2010); Mandsager et al. (2018).

  15. Robert Marchand: Billat et al. (2017).

  16. An eighty-year-old man: Lexell (1995).

  17. A study of twelve healthy volunteers: Kortebein et al. (2007).

  18. this muscle loss is called sarcopenia: T.N. Kim and Choi (2013).

  19. a broader clinical condition called frailty: Xue (2011).

  20. One study looked at sixty-two frail seniors: Tieland, Dirks, et al. (2012).

  21. “Carrying shaped our species”: Easter (2021).

  22. Many studies suggest that grip strength: Bohannon (2019); Hamer and O’Donovan (2017); Y. Kim et al. (2018); A.B. Newman et al. (2006).

  23. The consensus definition of sarcopenia: Cruz-Jentoft et al. (2019).

  24. In 1985, men ages twenty to twenty-four: Fain and Weatherford (2016).

Chapter 13. The Gospel of Stability

  1. Epidemiological studies tell us: Lieberman et al. (2021).

  2. According to the CDC: Dahlhamer (2018).

  3. Back pain, in particular: Shmagel et al. (2018).

  4. It is a leading cause of disability: Gaskin and Richard (2012).

  5. Studies of college-age athletes: Boneti Moreira et al. (2014).

  6. The theory behind DNS: Frank, Kobesova, and Kolar (2013).

  7. “DNS beautifully integrates”: Attia (2021a).

  8. Ten seconds is a respectable time: Araujo et al. (2022).

  9. “tech neck”: Tanweer (2021).

Chapter 14. Nutrition 3.0

  1. Richard Feynman being asked: Dye (1988).

  2. eating an ounce of tree nuts: Naghshi et al. (2020).

  3. eating twelve hazelnuts every day: Bao et al. (2013).

  4. drinking diet sodas and abdominal fat: Azad et al. (2017).

  5. Austin Bradford Hill: Hill (1965).

  6. a very well-publicized 2017 study: Schwingshackl, Schwedhelm, et al. (2018).

  7. someone who smokes cigarettes: Pesch et al. (2012); Proctor (2001); Sasco, Secretan, and Straif (2004); Youlden, Cramb, and Baade (2008).

  8. food is so complex: Ioannidis (2018); Moco et al. (2006); Ninonuevo et al. (2006); Wishart et al. (2007).

  9. “Nutritional epidemiology is a scandal”: Crowe (2018).

  10. David Allison ran an elegant experiment: Ejima et al. (2016).

  11. tainted by healthy user bias: Naimi et al. (2017).

  12. a recent study in JAMA: Biddinger et al. (2022).

  13. Now imagine trying to ensure: WHI (n.d.).

  14. In the end, despite all this effort: Howard et al. (2006).

  15. By the numbers, the nuts-or-olive-oil “Mediterranean” diet: Estruch et al. (2013).

  16. A post hoc analysis of PREDIMED data: Martínez-Lapiscina et al. (2013).

Chapter 15. Putting Nutritional Biochemistry into Practice

  1. a study published in Science: Colman et al. (2009).

  2. “Dieting Monkeys Offer Hope for Living Longer”: Wade (2009).

  3. in August 2012, another monkey study: Mattison et al. (2012).

  4. “Severe Diet Doesn’t Prolong Life”: Kolata (2012).

  5. lots of plants, lots of starch: Cordain, Miller, et al. (2000).

  6. very metabolically healthy: Cordain, Eaton, et al. (2002); Pontzer et al. (2018).

  7. One reason carbohydrate restriction is so effective: Gibson et al. (2015); Nymo et al. (2017); Phinney and Volek (2018); Sumithran et al. (2013).

  8. Being Latino meant: Oliveira, Cotrim, and Arrese (2019).

  9. chronic drinking has strong associations: Peng et al. (2020).

  10. mainly via its negative effect on sleep: C. Wang and Holtzman (2020).

  11. numerous well-publicized studies: Hines and Rimm (2001); Suzuki et al. (2009).

  12. the Mendelian randomization study in JAMA: Biddinger et al. (2022).

  13. But there is also evidence suggesting: Hanefeld et al. (1999); Kawano et al. (1999); H.-J. Lin et al. (2009); Standl, Schnell, and Ceriello (2011); Watanabe et al. (2011).

  14. A 2011 study looking at twenty thousand people: Pfister et al. (2011).

  15. Another study in 2019: Echouffo-Tcheugui et al. (2019).

  16. Foods high in protein and fat: Franz (1997).

  17. More than one study has found: W. Campbell et al. (2001).

  18. elderly people consuming that RDA of protein (0.8 g/kg/day): Wu (2016).

  19. one gram per pound of body weight per day: Baum, Kim, and Wolfe (2016).

  20. the ideal way to achieve this: Schoenfeld and Aragon (2018).

  21. older people might require more protein: Baum, Kim, and Wolfe (2016).

  22. the Healthy Aging and Body Composition Study: Houston et al. (2008).

  23. boosting protein intake even moderately: Rozentryt et al. (2010).

  24. Adding thirty grams of milk protein: Tieland, van de Rest, et al. (2012).

  25. giving elderly people supplements: Børsheim et al. (2009).

  26. Another study in men with type 2 diabetes: Nuttall and Gannon (2006).

  27. dietary fat also tends to leave one feeling more satiated: Boden et al. (2005); Holt et al. (1995); Samra (2010).

  28. Our per capita consumption of soybean oil: Blasbalg et al. (2011).

  29. the most comprehensive review of this topic: Abdelhamid et al. (2018).

  30. A more recent publication: Hooper et al. (2020).

  31. yet another recent review: Schwingshackl, Zähringer, et al. (2021).

  32. Fasting over long periods: Vendelbo et al. (2014).

  33. lack of nutrients accelerates autophagy: Bagherniya et al. (2018).

  34. and it activates FOXO: Gross, van den Heuvel, and Birnbaum (2008).

  35. The time-restricted mice gained less weight: Hatori et al. (2012).

  36. a sixteen-hour fast for a mouse: Jensen et al. (2013).

  37. A 2020 clinical trial by Ethan Weiss: Lowe et al. (2020).

  38. Two similar studies also found minimal benefit: Jamshed et al. (2019); D. Liu et al. (2022).

  39. subjects can indeed lose weight on alternate-day fasting diets: Varady and Gabel (2019).

  40. One small but revealing study: Templeman et al. (2021).

Chapter 16. The Awakening

  1. We now know that even one sleepless night: Dawson and Reid (1997); Lamond and Dawson (1999).

  2. sleep-deprived medical personnel: Mansukhani et al. (2012); Tang et al. (2019).

  3. Poor sleep dramatically increases one’s propensity: Iftikhar et al. (2015).

  4. up to and including type 2 diabetes: Shan et al. (2015).

  5. wreak havoc with the body’s hormonal balance: Leproult and Van Cauter (2010); Reutrakul and Van Cauter (2018); de Zambotti, Colrain, and Baker (2015).

  6. Good sleep, in terms of not only quantity: Goldstein and Walker (2014); Killgore (2013); Krause et al. (2017); Kuna et al. (2012); Motomura et al. (2013); Prather, Bogdan, and Hariri (2013); Rupp, Wesensten, and Balkin (2012); Van Dongen, Maislin, et al. (2003); Van Dongen, Baynard, et al. (2004); Yoo et al. (2007).

  7. It even cleans itself: Reddy and van der Werf (2020).

  8. sleeping well is essential to preserving our cognition: C. Wang and Holtzman (2020).

  9. “[The] decimation of sleep”: Walker (2017).

  10. Every animal engages in some form of sleep: Cirelli and Tononi (2008).

  11. studies conducted in dark caves: Zuccarelli et al. (2019).

  12. Even a single night of bad sleep: Cullen et al. (2019); Fullagar et al. (2015).

  13. Even our ability to perspire is impaired: Dewasmes et al. (1993); Kolka and Stephenson (1988); Sawka, Gonzalez, and Pandolf (1984).

  14. A 2014 observational study: Milewski et al. (2014).

  15. In one study, Stanford basketball players: Mah et al. (2011).

  16. LeBron James makes sleep a key part: Ferriss (2018).

  17. professional drivers displayed far worse reaction time: Jackson et al. (2013).

  18. But a survey conducted by AAA: AAA Foundation (2016).

  19. people who are sleep deprived: Hafner et al. (2017); Killgore (2013); Krause et al. (2017); J. Lim and Dinges (2008); Van Dongen, Maislin, et al. (2003).

  20. people who sleep less chronically: Oyetakin-White et al. (2015).

  21. Sleep researcher Eve van Cauter: Broussard, Ehrmann, et al. (2012).

  22. No fewer than nine different studies: Broussard, Ehrmann, et al. (2012); Broussard, Chapotot, et al. (2015); Buxton et al. (2010); Leproult, Holmbäck, and Van Cauter (2014); Nedeltcheva et al. (2009); Rao et al. (2015); Spiegel, Leproult, and Van Cauter (1999); Stamatakis and Punjabi (2010); Tasali et al. (2008).

  23. Multiple large meta-analyses: Iftikhar et al. (2015); Itani et al. (2017); Shan et al. (2015).

  24. Similar risk associations have been found: Itani et al. (2017).

  25. it also causes glucose to be released: Kuo et al. (2015).

  26. Studies by Eve van Cauter’s group: Spiegel, Tasali, et al. (2004); Spiegel, Leproult, L’hermite-Balériaux, et al. (2004).

  27. Follow-up studies by van Cauter’s group: Bosy-Westphal et al. (2008); Brondel et al. (2010); Broussard, Kilkus, et al. (2016); Calvin et al. (2013); Spaeth, Dinges, and Goel (2015).

  28. Two large meta-analyses: Itani et al. (2017); Yin et al. (2017).

  29. But one particularly interesting study: Dashti et al. (2019).

  30. The MR data confirmed the observational findings: Daghlas et al. (2019).

  31. chronic bad sleep as a powerful potential cause: C. Wang and Holtzman (2020).

  32. we sleep in a series of well-defined stages: Lendner et al. (2020).

  33. the brain clears out its cache: Diekelmann and Born (2010); Wilson and McNaughton (1994).

  34. Researchers have observed: Walker (2009).

  35. When we are young: A.K. Patel, Reddy, and Araujo (2022).

  36. REM sleep is especially helpful: C. Smith and Lapp (1991); Stickgold et al. (2000).

  37. Another very important function: van der Helm and Walker (2009); Hutchison and Rathore (2015).

  38. studies of combat veterans: Repantis et al. (2020).

  39. Perhaps most intriguing: Goldstein-Piekarski et al. (2015).

  40. enough to enter REM: Rasking et al. (2007).

  41. as social animals: Yamazaki et al. (2020).

  42. A few years ago, researchers in Rochester: Iliff et al. (2013).

  43. amyloid-beta and tau, the two proteins: Lucey, McCullough, et al. (2019).

  44. Broader studies have found: Branger et al. (2016); B. Brown et al. (2016); Ju et al. (2013); Spira et al. (2013); Sprecher et al. (2015).

  45. This can become a vicious cycle: C. Wang and Holtzman (2020).

  46. Also, up to half of people: Emamian et al. (2016).

  47. Insomnia affects 30 to 50 percent: Benito-León et al. (2009); Jack et al. (2013); A.S.P. Lim, Kowgier, et al. (2013); A.S.P. Lim, Yu, et al. (2013); Lobo et al. (2008); Osorio et al. (2011).

  48. One study linked poor sleep quality: Potvin et al. (2012).

  49. Meanwhile, superior sleep quality: A.S.P. Lim, Kowgier, et al. (2013); A.S.P. Lim, Yu, et al. (2013).

  50. Successfully treating sleep disturbance: Ancoli-Israel et al. (2008); Moraes et al. (2006).

  51. More research points: Winer et al. (2019).

  52. The first real blockbuster sleeping medication: Saul (2006).

  53. Currently, the US sleep medication market: Business Wire (2021).

  54. One study found that Ambien: Arbon, Knurowska, and Dijk (2015).

  55. a new class of sleep drugs: Herring et al. (2016).

  56. Quviviq (daridorexant): Ziemichód et al. (2022).

  57. Then there are the older benzodiazepine drugs: Picton, Marino, and Nealy (2018).

  58. especially if it also improves sleep architecture: Zheng et al. (2022).

  59. Keep in mind, however: Shahid et al. (2011).

  60. Studies have found that some individuals: Kalmbach et al. (2017).

  61. Not only does non-natural lighting: Hardeland (2013).

  62. One large-scale survey: Gradisar et al. (2013).

  63. according to research by Michael Gradisar: Gradisar et al. (2013).

  64. One of the signal events: Harding, Franks, and Wisden (2020).

  65. It’s counterintuitive: Ebrahim et al. (2013).

  66. More alarming is the finding: C. Smith and Smith (2003).

  67. Most people think of caffeine as a stimulant: Urry and Landolt (2015).

  68. But the half-life of caffeine: IOM (2001).

  69. This is why one of the primary techniques: Maurer et al. (2021).

  70. Another way to help cultivate: Dworak et al. (2007); Youngstedt et al. (2000).

  71. Another way to turn down: D. Kim et al. (2022).

Chapter 17. Work in Progress

  1. Another very direct way: CDC (2022f).

  2. a man named Ken Baldwin: Friend (2003).

  3. It’s not a surprise: Spillane et al. (2020).

  4. the CDC estimates: Strobe (2021).

  5. These “accidental” overdoses: CDC (2022a).

  6. They were slow-motion suicides: Case et al. (2015).

  7. This category of death: CDC (2022d).

  8. Middle-aged white men and women, in particular: Case and Deaton (2015).

  9. Surveys show that older Americans: Livingston (2019).

  10. Terrence Real’s book: Real (1998).

  11. as David Foster Wallace explained: Wallace (2009).

  12. “résumé virtues”: Brooks (2016).

  13. “When nothing seems to help”: Riis (1901).

  14. Clinical trials have found it to be effective: Asarnow et al. (2021); Linehan et al. (2006).

  15. exposing oneself to the fractal geometric patterns: Hagerhall (2008).

Disclosures

  1. For an up-to-date list of all my disclosures, please see https://peterattiamd.com/​about/ under the heading “Disclosures.”