CoChat
Sign Up
Cited by 253Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Modifiable Risk Factors for Alzheimer’s Disease

Open access
Edwards III, George A., Gamez, Nazaret, Escobedo Jr., Gabriel, Calderon, Olivia, Moreno-Gonzalez, Ines·2019·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2019.00146PMC PMC6601685
Open this paper in CoChat — free accountOpen PDF

Abstract

Since first described in the early 1900s, Alzheimer's disease (AD) has risen exponentially in prevalence and concern. Research still drives to understand the etiology and pathogenesis of this disease and what risk factors can attribute to AD. With a majority of AD cases being of sporadic origin, the increasing exponential growth of an aged population and a lack of treatment, it is imperative to discover an easy accessible preventative method for AD. Some risk factors can increase the propensity of AD such as aging, sex, and genetics. Moreover, there are also modifiable risk factors-in terms of treatable medical conditions and lifestyle choices-that play a role in developing AD. These risk factors have their own biological mechanisms that may contribute to AD etiology and pathological consequences. In this review article, we will discuss modifiable risk factors and discuss the current literature of how each of these factors interplay into AD development and progression and if strategically analyzed and treated, could aid in protection against this neurodegenerative disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnagi.2019.00146

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Part of the risk factors for cardiovascular disease are in common with Alzheimer's disease, including hypertension, dyslipidemia, diabetes, obesity, dietary factors, smoking, and physical activity.

    “This could explain why part of the risk factors for cardiovascular disease are in common with AD, including hypertension, dyslipidemia, diabetes, obesity, dietary factors, smoking, and physical activity (Figure 1B).”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [103]

    The Vascular Diseases section (page unavailable) explicitly identifies hypertension, diabetes, and hypercholesterolemia as risks shared by cardiovascular disease and AD; its Smoking section also links smoking to cardiovascular disease and dementia. The paper discusses diet and obesity in relation to diabetes and AD, but does not establish every item in the citing sentence as a shared cardiovascular–AD risk factor. Its Physical Activity section says it remains unknown whether exercise reduces the risk of developing AD. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Lifestyle is an important risk factor, where intellectual, physical, and social activities, as well as diet, may help to prevent Alzheimer's disease.

    “Thus, lifestyle is also an important risk factor, where intellectual, physical, and social activities, as well as diet, may help to prevent AD [1,22,100,101,102,103].”

    From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [103]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 219

  1. Abdullah L. Evans J. E. Emmerich T. Crynen G. Shackleton B. Keegan A. P.. (2017). APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical mild cognitive impairment/Alzheimer’s disease. Aging 9, 964– 985. 10.18632/aging.101203 28333036 PMC5391242 · DOI
  2. Abedini A. Schmidt A. M. States U. (2015). Mechanisms of islet amyloidosis toxicity in type 2 diabetes. FEBS Lett. 587, 1119– 1127. 10.1016/j.febslet.2013.01.017 23337872 PMC4557799 · DOI
  3. Abner E. L. Nelson P. T. Jicha G. A. Fardo D. W. Schmitt F. A. Kryscio R. J. (2018). Cigarette smoking and risk of dementia in a Kentucky cohort: a competing risk analysis. Alzheimers Dement. 14: 973 10.1016/j.jalz.2018.06.1306 PMC6915304 30856115 · DOI
  4. Adlard P. A. Perreau V. M. Pop V. Cotman C. W. (2005). Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J. Neurosci. 25, 4217– 4221. 10.1523/JNEUROSCI.0496-05.2005 15858047 PMC6725122 · DOI
  5. Air E. L. Kissela B. M. (2007). Diabetes, the metabolic syndrome, and ischemic stroke: epidemiology and possible mechanisms. Diabetes Care 30, 3131– 3140. 10.2337/dc06-1537 17848611 · DOI
  6. Alkadhi K. A. Dao A. T. (2018). Exercise decreases BACE and APP levels in the hippocampus of a rat model of Alzheimer’s disease. Mol. Cell. Neurosci. 86, 25– 29. 10.1016/j.mcn.2017.11.008 29128320 · DOI
  7. Amatniek J. C. Hauser W. A. Delcastillo-Castaneda C. Jacobs D. M. Marder K. Bell K.. (2006). Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia 47, 867– 872. 10.1111/j.1528-1167.2006.00554.x 16686651 · DOI
  8. Anstey K. J. von Sanden C. Salim A. O’Kearney R. (2007). Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies. Am. J. Epidemiol. 166, 367– 378. 10.1093/aje/kwm116 17573335 · DOI · Paper page
  9. Arvanitakis Z. Leurgans S. E. Wang Z. Wilson R. S. Bennett D. A. Schneider J. A. (2011). Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann. Neurol. 69, 320– 327. 10.1002/ana.22112 21387377 PMC3228518 · DOI · Paper page
  10. Baek S.-S. Kim S.-H. (2016). Treadmill exercise ameliorates symptoms of Alzheimer disease through suppressing microglial activation-induced apoptosis in rats. J. Exerc. Rehabil. 12, 526– 534. 10.12965/jer.1632858.429 28119873 PMC5227313 · DOI
  11. Baglietto-Vargas D. Shi J. Yaeger D. M. Ager R. LaFerla F. M. (2016). Diabetes and Alzheimer’s disease crosstalk. Neurosci. Biobehav. Rev. 64, 272– 287. 10.1016/j.neubiorev.2016.03.005 26969101 · DOI
  12. Bakker A. Krauss G. L. Albert M. S. Speck C. L. Jones L. R. Stark C. E.. (2012). Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74, 467– 474. 10.1016/j.neuron.2012.03.023 22578498 PMC3351697 · DOI
  13. Ballard C. Gauthier S. Corbett A. Brayne C. Aarsland D. Jones E.. (2011). Alzheimer’s disease. Lancet 377, 1019– 1031. 10.1016/S0140-6736(10)61349-9 21371747 · DOI · Paper page
  14. Barnes D. E. Yaffe K. Byers A. L. McCormick M. Schaefer C. Whitmer R. A. (2012). Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch. Gen. Psychiatry 69, 493– 498. 10.1001/archgenpsychiatry.2011.1481 22566581 PMC3704214 · DOI
  15. Bateman R. J. Munsell L. Y. Morris J. C. Swarm R. Yarasheski K. E. Holtzman D. M. (2006). Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat. Med. 12, 856– 861. 10.1038/nm1438 16799555 PMC2983090 · DOI · Paper page
  16. Bazil C. W. (2003). Epilepsy and sleep disturbance. Epilepsy Behav. 4, 39– 45. 10.1016/j.yebeh.2003.07.005 14527482 · DOI
  17. Beach T. G. Wilson J. R. Sue L. I. Newell A. Poston M. Cisneros R.. (2007). Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol. 113, 13– 21. 10.1007/s00401-006-0136-y 17021755 · DOI
  18. Belarbi K. Burnouf S. Fernandez-Gomez F. J. Laurent C. Lestavel S. Figeac M.. (2011). Beneficial effects of exercise in a transgenic mouse model of Alzheimer’s disease-like Tau pathology. Neurobiol. Dis. 43, 486– 494. 10.1016/j.nbd.2011.04.022 21569847 · DOI
  19. Bellou V. Belbasis L. Tzoulaki I. Middleton L. T. Ioannidis J. P. A. Evangelou E. (2017). Systematic evaluation of the associations between environmental risk factors and dementia: an umbrella review of systematic reviews and meta-analyses. Alzheimers Dement. 13, 406– 418. 10.1016/j.jalz.2016.07.152 27599208 · DOI
  20. Benedictus M. R. van Harten A. C. Leeuwis A. E. Koene T. Scheltens P. Barkhof F.. (2015). White matter hyperintensities relate to clinical progression in subjective cognitive decline. Stroke 46, 2661– 2664. 10.1161/strokeaha.115.009475 26173729 · DOI
  21. Berhanu W. M. Yaşar F. Hansmann U. H. E. (2013). In silico cross seeding of Aβ and amylin fibril-like oligomers. ACS Chem. Neurosci. 4, 1488– 1500. 10.1021/cn400141x 24007594 PMC3837374 · DOI
  22. Berti V. Walters M. Sterling J. Quinn C. G. Logue M. Andrews R.. (2018). Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults. Neurology 90, e1789– e1798. 10.1212/wnl.0000000000005527 29653991 PMC5957301 · DOI
  23. Blennow K. Brody D. L. Kochanek P. M. Levin H. McKee A. Ribbers G. M.. (2016). Traumatic brain injuries. Nat. Rev. Dis. Primers 2: 16084. 10.1038/nrdp.2016.84 27853132 · DOI
  24. Boccardi V. Esposito A. Rizzo M. R. Marfella R. Barbieri M. Paolisso G. (2013). Mediterranean diet, telomere maintenance and health status among elderly. PLoS One 8: e62781. 10.1371/journal.pone.0062781 23646142 PMC3640022 · DOI
  25. Bonanni E. Maestri M. Tognoni G. Fabbrini M. Nucciarone B. Manca M. L.. (2005). Daytime sleepiness in mild and moderate Alzheimer’s disease and its relationship with cognitive impairment. J. Sleep Res. 14, 311– 317. 10.1016/j.sleep.2005.05.001 16120107 · DOI
  26. Bos I. Vos S. J. Frölich L. Kornhuber J. Wiltfang J. Maier W.. (2017). The frequency and influence of dementia risk factors in prodromal Alzheimer’s disease. Neurobiol. Aging 56, 33– 40. 10.1016/j.neurobiolaging.2017.03.034 28482212 · DOI
  27. Brenner D. E. Kukull W. A. van Belle G. Bowen J. D. McCormick W. C. Teri L.. (1993). Relationship between cigarette smoking and Alzheimer’s disease in a population-based case-control study. Neurology 43, 293– 300. 10.1212/wnl.43.2.293 8437692 · DOI
  28. Bretherton-Watt D. Bloom S. R. (1991). Islet amyloid polypeptide: the cause of type-2 diabetes? Trends Endocrinol. Metab. 2, 203– 206. 10.1016/1043-2760(91)90025-I 18411183 · DOI
  29. Breunig J. J. Guillot-Sestier M. V. Town T. (2013). Brain injury, neuroinflammation and Alzheimer’s disease. Front. Aging Neurosci. 5: 26. 10.3389/fnagi.2013.00026 23874297 PMC3708131 · DOI
  30. Caruso A. Nicoletti F. Mango D. Saidi A. Orlando R. Scaccianoce S. (2018). Stress as risk factor for Alzheimer’s disease. Pharmacol. Res. 132, 130– 134. 10.1016/j.phrs.2018.04.017 29689315 · DOI
  31. Chatterjee S. Peters S. A. E. Woodward M. Mejia Arango S. Batty G. D. Beckett N.. (2016). Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia. Diabetes Care 39, 300– 307. 10.2337/dc15-1588 26681727 PMC4722942 · DOI · Paper page
  32. Chen C. P. Alder J. T. Bowen D. M. Esiri M. M. McDonald B. Hope T.. (1996). Presynaptic serotonergic markers in community-acquired cases of Alzheimer’s disease: correlations with depression and neuroleptic medication. J. Neurochem. 66, 1592– 1598. 10.1046/j.1471-4159.1996.66041592.x 8627315 · DOI
  33. Chen X. H. Johnson V. E. Uryu K. Trojanowski J. Q. Smith D. H. (2009). A lack of amyloid β plaques despite persistent accumulation of amyloid β in axons of long-term survivors of traumatic brain injury. Brain Pathol. 19, 214– 223. 10.1111/j.1750-3639.2008.00176.x 18492093 PMC3014260 · DOI · Paper page
  34. Choi S. H. Bylykbashi E. Chatila Z. K. Lee S. W. Pulli B. Clemenson G. D.. (2018). Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science 361: eaan8821. 10.1126/science.aan8821 30190379 PMC6149542 · DOI · Paper page
  35. Clark A. de Koning E. J. P. Hattersley A. T. Hansen B. C. Yajnik C. S. Poulton J. (1995). Pancreatic pathology in non-insulin dependent diabetes (NIDDM). Diabetes Res. Clin. Pract. 28, S39– S47. 10.1016/0168-8227(95)01075-o 8529518 · DOI
  36. Corbett B. F. You J. C. Zhang X. Pyfer M. S. Tosi U. Iascone D. M.. (2017). ΔFosB regulates gene expression and cognitive dysfunction in a mouse model of Alzheimer’s disease. Cell Rep. 20, 344– 355. 10.1016/j.celrep.2017.06.040 28700937 PMC5785235 · DOI
  37. Cordero J. G. García-Escudero R. Avila J. Gargini R. García-Escudero V. (2018). Benefit of oleuropein aglycone for Alzheimer’s disease by promoting autophagy. Oxid. Med. Cell. Longev. 2018: 5010741. 10.1155/2018/5010741 29675133 PMC5838478 · DOI
  38. Cretin B. Sellal F. Philippi N. Bousiges O. Di Bitonto L. Martin-Hunyadi C.. (2016). Epileptic prodromal Alzheimer’s disease, a retrospective study of 13 new cases: expanding the spectrum of Alzheimer’s disease to an epileptic variant? J. Alzheimers Dis. Park. 52, 1125– 1133. 10.3233/JAD-150096 27104892 · DOI
  39. Cummings J. L. Doody R. Clark C. (2007). Disease-modifying therapies for Alzheimer disease: challenges to early intervention. Neurology 69, 1622– 1634. 10.1212/01.wnl.0000295996.54210.69 17938373 · DOI
  40. Curto M. Martocchia A. Ferracuti S. Comite F. Scaccianoce S. Girardi P.. (2017). Increased total urinary cortisol (tUC) and serum brain-derived neurotrophic factor (BDNF) ratio in Alzheimer disease (AD)-affected patients. Alzheimer Dis. Assoc. Disord. 31, 173– 176. 10.1097/wad.0000000000000156 27196536 · DOI
  41. Das M. Maeda S. Hu B. Yu G. Q. Guo W. Lopez I.. (2018). Neuronal levels and sequence of tau modulate the power of brain rhythms. Neurobiol. Dis. 117, 181– 188. 10.1016/j.nbd.2018.05.020 29859869 · DOI
  42. Davinelli S. Sapere N. Zella D. Bracale R. Intrieri M. Scapagnini G. (2012). Pleiotropic protective effects of phytochemicals in Alzheimer’s disease. Oxid. Med. Cell. Longev. 2012: 386527. 10.1155/2012/386527 22690271 PMC3368517 · DOI
  43. de la Torre J. (2018). The vascular hypothesis of Alzheimer’s disease: a key to preclinical prediction of dementia using neuroimaging. J. Alzheimers Dis. 63, 35– 52. 10.3233/JAD-180004 29614675 · DOI
  44. de Oliveira F. Bertolucci P. F. Chen E. Smith M. (2015). Assessment of risk factors for earlier onset of sporadic Alzheimer’s disease dementia. Neurol. India 62, 625– 630. 10.4103/0028-3886.149384 25591674 · DOI
  45. Deng J. Zhou D. H. D. Li J. Wang Y. J. Gao C. Chen M. (2006). A 2-year follow-up study of alcohol consumption and risk of dementia. Clin. Neurol. Neurosurg. 108, 378– 383. 10.1016/j.clineuro.2005.06.005 16084641 · DOI
  46. Dhouafli Z. Cuanalo-Contreras K. Hayouni E. A. Mays C. E. Soto C. Moreno-Gonzalez I. (2018). Inhibition of protein misfolding and aggregation by natural phenolic compounds. Cell. Mol. Life Sci. 75, 3521– 3538. 10.1007/s00018-018-2872-2 30030591 PMC11105286 · DOI
  47. Di Meco A. Joshi Y. B. Praticò D. (2014). Sleep deprivation impairs memory, tau metabolism and synaptic integrity of a mouse model of Alzheimer’s disease with plaques and tangles. Neurobiol. Aging 35, 1813– 1820. 10.1016/j.neurobiolaging.2014.02.011 24629673 · DOI · Paper page
  48. Dickerson T. J. Janda K. D. (2002). A previously undescribed chemical link between smoking and metabolic disease. Proc. Natl. Acad. Sci. U S A 99, 15084– 15088. 10.1073/pnas.222561699 12403823 PMC137547 · DOI
  49. Dickstein D. L. Walsh J. Brautigam H. Stockton S. D. Jr. Gandy S. Hof P. R. (2010). Role of vascular risk factors and vascular dysfunction in Alzheimer’s disease. Mt. Sinai J. Med. 77, 82– 102. 10.1002/msj.20155 20101718 PMC2918901 · DOI
  50. Diem S. J. Blackwell T. L. Stone K. L. Yaffe K. Tranah G. Cauley J. A.. (2016). Measures of sleep-wake patterns and risk of mild cognitive impairment or dementia in older women. Am. J. Geriatr. Psychiatry 24, 248– 258. 10.1016/j.jagp.2015.12.002 26964485 PMC4807599 · DOI
  51. Ding S. Fellin T. Zhu Y. Lee S.-Y. Auberson Y. P. Meaney D. F.. (2007). Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus. J. Neurosci. 27, 10674– 10684. 10.1523/JNEUROSCI.2001-07.2007 17913901 PMC2917229 · DOI
  52. Diniz B. S. Butters M. A. Albert S. M. Dew M. A. Reynolds C. F. III. (2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br. J. Psychiatry 202, 329– 335. 10.1192/bjp.bp.112.118307 23637108 PMC3640214 · DOI · Paper page
  53. Dong H. Csernansky J. G. (2009). Effects of stress and stress hormones on amyloid-β protein and plaque deposition. J. Alzheimers Dis. 18, 459– 469. 10.3233/jad-2009-1152 19584430 PMC2905685 · DOI
  54. Drevets W. C. Rubin E. H. (1989). Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. Biol. Psychiatry 25, 39– 48. 10.1016/0006-3223(89)90145-5 2912509 · DOI
  55. Durazzo T. C. Meyerhoff D. J. Nixon S. J. (2010). Chronic cigarette smoking: implications for neurocognition and brain neurobiology. Int. J. Environ. Res. Public Health 7, 3760– 3791. 10.3390/ijerph7103760 21139859 PMC2996190 · DOI
  56. Edwards G. III. Moreno-Gonzalez I. Soto C. (2017). Amyloid-β and tau pathology following repetitive mild traumatic brain injury. Biochem. Biophys. Res. Commun. 483, 1137– 1142. 10.1016/j.bbrc.2016.07.123 27492070 · DOI · Paper page
  57. Ellis R. J. Caligiuri M. Galasko D. Thal L. J. (1996). Extrapyramidal motor signs in clinically diagnosed Alzheimer disease. Alzheimer Dis. Assoc. Disord. 10, 103– 114. 10.1097/00002093-199601020-00008 8727172 · DOI
  58. Erickson K. I. Voss M. W. Prakash R. S. Basak C. Szabo A. Chaddock L.. (2011). Exercise training increases size of hippocampus and improves memory. Proc. Natl. Acad. Sci. U S A 108, 3017– 3022. 10.1073/pnas.1015950108 21282661 PMC3041121 · DOI · Paper page
  59. Extance A. (2010). Alzheimer’s failure raises questions about disease-modifying strategies. Nat. Rev. Drug Discov. 9, 749– 751. 10.1038/nrd3288 20885394 · DOI
  60. Fann J. R. Ribe A. R. Pedersen H. S. Fenger-Grøn M. Christensen J. Benros M. E.. (2018). Long-term risk of dementia among people with traumatic brain injury in Denmark: a population-based observational cohort study. Lancet Psychiatry 5, 424– 431. 10.1016/s2215-0366(18)30065-8 29653873 · DOI · Paper page
  61. Fernandez G. M. Savage L. M. (2017). Adolescent binge ethanol exposure alters specific forebrain cholinergic cell populations and leads to selective functional deficits in the prefrontal cortex. Neuroscience 361, 129– 143. 10.1016/j.neuroscience.2017.08.013 28807788 PMC5609857 · DOI
  62. Ferris L. T. Williams J. S. Shen C. L. (2007). The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med. Sci. Sports Exerc. 39, 728– 734. 10.1249/mss.0b013e31802f04c7 17414812 · DOI · Paper page
  63. Frere S. Slutsky I. (2018). Alzheimer’s disease: from firing instability to homeostasis network collapse. Neuron 97, 32– 58. 10.1016/j.neuron.2017.11.028 29301104 · DOI
  64. Gardener S. Gu Y. Rainey-Smith S. R. Keogh J. B. Clifton P. M. Mathieson S. L.. (2012). Adherence to a Mediterranean diet and Alzheimer’s disease risk in an Australian population. Transl. Psychiatry 2: e164. 10.1038/tp.2012.91 23032941 PMC3565821 · DOI
  65. Gentleman S. M. Leclercq P. D. Moyes L. Graham D. I. Smith C. Griffin W. S. T.. (2004). Long-term intracerebral inflammatory response after traumatic brain injury. Forensic Sci. Int. 146, 97– 104. 10.1016/j.forsciint.2004.06.027 15542269 · DOI · Paper page
  66. Gottesman R. F. Albert M. S. Alonso A. Coker L. H. Coresh J. Davis S. M.. (2017a). Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) cohort. JAMA Neurol. 74, 1246– 1254. 10.1001/jamaneurol.2017.1658 28783817 PMC5710244 · DOI · Paper page
  67. Graham J. E. Rockwood K. Beattie B. L. McDowell I. Eastwood R. Gauthier S. (1996). Standardization of the diagnosis of dementia in the canadian study of health and aging. Neuroepidemiology 15, 246– 256. 10.1159/000109914 8878077 · DOI
  68. Graves A. B. White E. Koepsell T. D. Reifler B. V. van Belle G. Larson E. B.. (1990). The association between head trauma and Alzheimer’s disease. Am. J. Epidemiol. 131, 491– 501. 10.1093/oxfordjournals.aje.a115523 2405648 · DOI
  69. Grossi C. Rigacci S. Ambrosini S. Ed Dami T. Luccarini I. Traini C.. (2013). The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology. PLoS One 8: e71702. 10.1371/journal.pone.0071702 23951225 PMC3738517 · DOI
  70. Gu Y. Honig L. S. Schupf N. Lee J. H. Luchsinger J. A. Stern Y.. (2015). Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population. Age 37: 24. 10.1007/s11357-015-9758-0 25750063 PMC4352412 · DOI
  71. Guo J. Shou C. Meng L. Jiang B. Dong B. Yao L.. (2007). Neuronal protein synuclein γ predicts poor clinical outcome in breast cancer. Int. J. Cancer 121, 1296– 1305. 10.1002/ijc.22763 17534899 · DOI
  72. Guzman-Ramos K. Moreno-Castilla P. Castro-Cruz M. McGaugh J. L. Martinez-Coria H. LaFerla F. M. (2012). Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer’s disease. Learn. Mem. 19, 453– 460. 10.1101/lm.026070.112 22984283 · DOI · Paper page
  73. Haglund M. Passant U. Sjöbeck M. Ghebremedhin E. Englund E. (2006). Cerebral amyloid angiopathy and cortical microinfarcts as putative substrates of vascular dementia. Int. J. Geriatr. Psychiatry 21, 681– 687. 10.1002/gps.1550 16802283 · DOI
  74. Haring B. Wu C. Mossavar-Rahmani Y. Snetselaar L. Brunner R. Wallace R. B.. (2016). No association between dietary patterns and risk for cognitive decline in older women with 9-year follow-up: data from the women’s health initiative memory study. J. Acad. Nutr. Diet. 116, 921– 930. 10.1016/j.jand.2015.12.017 27050728 PMC4884559 · DOI
  75. Hatzinger M. Z’Brun A. Hemmeter U. Seifritz E. Baumann F. Holsboer-Trachsler E.. (1995). Hypothalamic-pituitary-adrenal system function in patients with Alzheimer’s disease. Neurobiol. Aging 16, 205– 209. 10.1016/0197-4580(94)00159-6 7777138 · DOI
  76. Heffernan M. Mather K. A. Xu J. Assareh A. A. Kochan N. A. Reppermund S.. (2016). Alcohol consumption and incident dementia: evidence from the sydney memory and ageing study. J. Alzheimers Dis. 52, 529– 538. 10.3233/jad-150537 27031466 · DOI
  77. Hellström-Lindahl E. Court J. Keverne J. Svedberg M. Lee M. Marutle A.. (2004). Nicotine reduces Aβ in the brain and cerebral vessels of APPsw mice. Eur. J. Neurosci. 19, 2703– 2710. 10.1111/j.0953-816X.2004.03377.x 15147304 · DOI
  78. Hemming M. L. Selkoe D. J. (2005). Amyloid β-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J. Biol. Chem. 280, 37644– 37650. 10.1074/jbc.M508460200 16154999 PMC2409196 · DOI
  79. Hemming M. L. Selkoe D. J. Farris W. (2007). Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid β-protein metabolism in mouse models of Alzheimer disease. Neurobiol. Dis. 26, 273– 281. 10.1016/j.nbd.2007.01.004 17321748 PMC2377010 · DOI
  80. Heymann D. Stern Y. Cosentino S. Tatarina-Nulman O. Dorrejo J. N. Gu Y. (2016). The association between alcohol use and the progression of Alzheimer’s disease. Curr. Alzheimer Res. 13, 1356– 1362. 10.2174/1567205013666160603005035 27628432 PMC5526221 · DOI
  81. Hongpaisan J. Sun M.-K. Alkon D. L. (2011). PKC activation prevents synaptic loss, a elevation and cognitive deficits in Alzheimer’s disease transgenic mice. J. Neurosci. 31, 630– 643. 10.1523/JNEUROSCI.5209-10.2011 21228172 PMC6623433 · DOI
  82. Horvath A. Szucs A. Barcs G. Noebels J. L. Kamondi A. (2016). Epileptic seizures in Alzheimer disease: a review. Alzheimer Dis. Assoc. Disord. 30, 186– 192. 10.1097/wad.0000000000000134 26756385 · DOI
  83. Hu X. Song C. Fang M. Li C. (2018). Simvastatin inhibits the apoptosis of hippocampal cells in a mouse model of Alzheimer’s disease. Exp. Ther. Med 15, 1795– 1802. 10.3892/etm.2017.5620 29434767 PMC5776644 · DOI
  84. Jacobsen J. Siesser W. B. Sachs B. D. Peterson S. Cools M. J. Setola V.. (2012). Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. Mol. Psychiatry 17, 694– 704. 10.1038/mp.2011.50 21537332 PMC3536482 · DOI
  85. Janson J. Laedtke T. Parisi J. E. O’Brien P. Petersen R. C. Butler P. C. (2004). Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53, 474– 481. 10.2337/diabetes.53.2.474 14747300 · DOI · Paper page
  86. Janson J. Soeller W. C. Roche P. C. Nelson R. T. Torchia A. J. Kreutter D. K.. (1996). Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proc. Natl. Acad. Sci. U S A 93, 7283– 7288. 10.1073/pnas.93.14.7283 8692984 PMC38975 · DOI
  87. Jee Y.-S. Ko I.-G. Sung Y.-H. Lee J.-W. Kim Y.-S. Kim S.-E.. (2008). Effects of treadmill exercise on memory and c-Fos expression in the hippocampus of the rats with intracerebroventricular injection of streptozotocin. Neurosci. Lett. 443, 188– 192. 10.1016/j.neulet.2008.07.078 18687381 · DOI
  88. Jin J.-J. Ko I.-G. Kim S.-E. Shin M.-S. Kim S.-H. Jee Y.-S. (2014). Swimming exercise ameliorates multiple sclerosis-induced impairment of short-term memory by suppressing apoptosis in the hippocampus of rats. J. Exerc. Rehabil. 10, 69– 74. 10.12965/jer.140103 24877040 PMC4025552 · DOI
  89. Johnson V. E. Stewart W. Smith D. H. (2012). Widespread tau and amyloid-β pathology many years after a single traumatic brain injury in humans. Brain Pathol. 22, 142– 149. 10.1111/j.1750-3639.2011.00513.x 21714827 PMC3979351 · DOI · Paper page
  90. Kalmijn S. van Boxtel M. P. J. Verschuren M. W. M. Jolles J. Launer L. J. (2002). Cigarette smoking and alcohol consumption in relation to cognitive performance in middle age. Am. J. Epidemiol. 156, 936– 944. 10.1093/aje/kwf135 12419766 · DOI · Paper page
  91. Kamenetz F. Tomita T. Hsieh H. Seabrook G. Borchelt D. Iwatsubo T. (2003). APP processing and synaptic function. Neuron 37, 925– 937. 10.1016/S0896-6273(03)00124-7 12670422 · DOI · Paper page
  92. Kang J. E. Lim M. M. Bateman R. J. Lee J. J. Smyth L. P. Cirrito J. R.. (2009). Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science 326, 1005– 1007. 10.1126/science.1180962 19779148 PMC2789838 · DOI · Paper page
  93. Kapurniotu A. Tatarek-Nossol M. Andreetto E. Frank R. Yan L.-M. Velkova A. (2010). Identification of hot regions of the Aβ-IAPP interaction interface as high-affinity binding sites in both cross- and self-association. Angew. Chem. Int. Ed Engl. 49, 3081– 3085. 10.1002/anie.200904902 20309983 · DOI
  94. Kilander L. Andrén B. Nyman H. Lind L. Boberg M. Lithell H. (1998). Atrial fibrillation is an independent determinant of low cognitive function: a cross-sectional study in elderly men. Stroke 29, 1816– 1820. 10.1161/01.str.29.9.1816 9731601 · DOI
  95. Kim B.-K. Shin M.-S. Kim C.-J. Baek S.-B. Ko Y.-C. Kim Y.-P. (2014). Treadmill exercise improves short-term memory by enhancing neurogenesis in amyloid β-induced Alzheimer disease rats. J. Exerc. Rehabil. 10, 2– 8. 10.12965/jer.140086 24678498 PMC3952831 · DOI
  96. Kivipelto M. Solomon A. Ahtiluoto S. Ngandu T. Lehtisalo J. Antikainen R.. (2013). The finnish geriatric intervention study to prevent cognitive impairment and disability (FINGER): study design and progress. Alzheimers Dement. 9, 657– 665. 10.1016/j.jalz.2012.09.012 23332672 · DOI · Paper page
  97. Koo J.-H. Kang E.-B. Oh Y.-S. Yang D.-S. Cho J.-Y. (2017). Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer’s disease. Exp. Neurol. 288, 142– 152. 10.1016/j.expneurol.2016.11.014 27889467 · DOI
  98. Kramer A. F. Hahn S. Cohen N. J. Banich M. T. McAuley E. Harrison C. R.. (1999). Ageing, fitness and neurocognitive function. Nature 400, 418– 419. 10.1038/22682 10440369 · DOI · Paper page
  99. Kumamaru E. Numakawa T. Adachi N. Yagasaki Y. Izumi A. Niyaz M.. (2008). Glucocorticoid prevents brain-derived neurotrophic factor-mediated maturation of synaptic function in developing hippocampal neurons through reduction in the activity of mitogen-activated protein kinase. Mol. Endocrinol. 22, 546– 558. 10.1210/me.2007-0264 18096693 PMC5419617 · DOI
  100. Kwok C. S. Loke Y. K. Hale R. Potter J. F. Myint P. K. (2011). Atrial fibrillation and incidence of dementia: a systematic review and meta-analysis. Neurology 76, 914– 922. 10.1212/WNL.0b013e31820f2e38 21383328 · DOI
  101. Lahiri D. K. Utsuki T. Chen D. Farlow M. R. Shoaib M. Ingram D. K.. (2002). Nicotine reduces the secretion of Alzheimer’s β-amyloid precursor protein containing β-amyloid peptide in the rat without altering synaptic proteins. Ann. N Y Acad. Sci. 965, 364– 372. 10.1111/j.1749-6632.2002.tb04178.x 12105112 · DOI
  102. Langbaum J. B. S. Chen K. Launer L. J. Fleisher A. S. Lee W. Liu X.. (2012). Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons. Neurobiol. Aging 33, 827.e11– 827.e19. 10.1016/j.neurobiolaging.2011.06.020 21821316 PMC3236809 · DOI
  103. Launer L. J. Ross G. W. Petrovitch H. Masaki K. Foley D. White L. R.. (2000). Midlife blood pressure and dementia: the honolulu-asia aging study. Neurobiol. Aging 21, 49– 55. 10.1016/S0197-4580(00)00096-8 10794848 · DOI · Paper page
  104. Law L. L. Sprecher K. E. Dougherty R. J. Edwards D. F. Koscik R. L. Gallagher C. L.. (2019). Cardiorespiratory fitness modifies influence of sleep problems on cerebrospinal fluid biomarkers in an at-risk cohort. J. Alzheimers Dis. 69, 111– 121. 10.3233/JAD-180291 30958346 PMC6675618 · DOI
  105. Lee P. N. (1994). Smoking and Alzheimer’s disease: a review of the epidemiological evidence. Neuroepidemiology 13, 131– 144. 10.1159/000110372 8090255 · DOI
  106. Leem Y. H. Lim H. J. Shim S. B. Cho J. Y. Kim B. S. Han P. L. (2009). Repression of tau hyperphosphorylation by chronic endurance exercise in aged transgenic mouse model of tauopathies. J. Neurosci. Res. 87, 2561– 2570. 10.1002/jnr.22075 19360903 · DOI
  107. Li P. Hsiao I. T. Liu C. Y. Chen C. H. Huang S. Y. Yen T. C.. (2017). β-amyloid deposition in patients with major depressive disorder with differing levels of treatment resistance: a pilot study. EJNMMI Res. 7: 24. 10.1186/s13550-017-0273-4 28324341 PMC5360749 · DOI
  108. Li G. Mayer C. L. Morelli D. Millard S. P. Raskind W. H. Petrie E. C.. (2017). Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults. Neurology 89, 1251– 1255. 10.1212/WNL.0000000000004392 28821686 PMC5606918 · DOI
  109. Li J. Wang Y. J. Zhang M. Xu Z. Q. Gao C. Y. Fang C. Q.. (2011). Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease. Neurology 76, 1485– 1491. 10.1212/WNL.0b013e318217e7a4 21490316 · DOI · Paper page
  110. Li X. Song D. Leng S. X. (2015). Link between type 2 diabetes and Alzheimer’s disease: from epidemiology to mechanism and treatment. Clin. Interv. Aging 10, 549– 560. 10.2147/CIA.S74042 25792818 PMC4360697 · DOI
  111. Liu Y. Liu F. Grundke-Iqbal I. Iqbal K. Gong C. X. (2009). Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer’s disease. J. Neurochem. 111, 242– 249. 10.1111/j.1471-4159.2009.06320.x 19659459 PMC2760012 · DOI
  112. Liu Y. Liu F. Iqbal K. Grundke-Iqbal I. Gong C. X. (2008). Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett. 582, 359– 364. 10.1016/j.febslet.2007.12.035 18174027 PMC2247364 · DOI
  113. Liu H. Zhao G. Cai K. Zhao H. Shi L. (2011). Treadmill exercise prevents decline in spatial learning and memory in APP/PS1 transgenic mice through improvement of hippocampal long-term potentiation. Behav. Brain Res. 218, 308– 314. 10.1016/j.bbr.2010.12.030 21192984 · DOI
  114. Liu H.-L. Zhao G. Zhang H. Shi L. D. (2013). Long-term treadmill exercise inhibits the progression of Alzheimer’s disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice. Behav. Brain Res. 256, 261– 272. 10.1016/j.bbr.2013.08.008 23968591 · DOI
  115. Livingston G. Sommerlad A. Orgeta V. Costafreda S. G. Huntley J. Ames D.. (2017). Dementia prevention, intervention and care. Lancet 390, 2673– 2734. 10.1016/S0140-6736(17)31363-6 28735855 · DOI · Paper page
  116. Loewenstein R. J. Weingartner H. Gillin J. C. Kaye W. Ebert M. Mendelson W. B. (1982). Disturbances of sleep and cognitive functioning in patients with dementia. Neurobiol. Aging 3, 371– 377. 10.1016/0197-4580(82)90025-2 7170053 · DOI
  117. Love S. Miners J. S. (2016). Cerebrovascular disease in ageing and Alzheimer’s disease. Acta Neuropathol. 131, 645– 658. 10.1007/s00401-015-1522-0 26711459 PMC4835514 · DOI · Paper page
  118. Lu Y. Dong Y. Tucker D. Wang R. Ahmed M. E. Brann D.. (2017). Treadmill exercise exerts neuroprotection and regulates microglial polarization and oxidative stress in a streptozotocin-induced rat model of sporadic Alzheimer’s disease. J. Alzheimers Dis. 56, 1469– 1484. 10.3233/JAD-160869 28157094 PMC5450951 · DOI
  119. Luchsinger J. A. Gustafson D. R. (2009). Adiposity, type 2 diabetes and Alzheimer’s disease. J. Alzheimers Dis. 16, 693– 704. 10.3233/JAD-2009-1022 19387106 PMC2705908 · DOI
  120. Luchsinger J. A. Reitz C. Honig L. S. Tang M. X. Shea S. Mayeux R. (2005). Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology 65, 545– 551. 10.1212/01.WNL.0000172914.08967.dc 16116114 PMC1619350 · DOI · Paper page
  121. Luchsinger J. A. Tang M.-X. Siddiqui M. Shea S. Mayeux R. (2004). Alcohol intake and risk of dementia. J. Am. Geriatr. Soc. 52, 540– 546. 10.1111/j.1532-5415.2004.52159.x 15066068 · DOI
  122. Lundgaard I. Wang W. Eberhardt A. Vinitsky H. S. Reeves B. C. Peng S.. (2018). Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function. Sci. Rep. 8: 2246. 10.1038/s41598-018-20424-y 29396480 PMC5797082 · DOI
  123. Lyketsos C. G. Tune L. E. Pearlson G. Steele C. (1996). Major depression in Alzheimer’s disease: an interaction between gender and family history. Psychosomatics 37, 380– 384. 10.1016/S0033-3182(96)71552-9 8701017 · DOI
  124. Magariños A. M. Orchinik M. McEwen B. S. (1998). Morphological changes in the hippocampal CA3 region induced by non-invasive glucocorticoid administration: a paradox. Brain Res. 809, 314– 318. 10.1016/s0006-8993(98)00882-8 9853126 · DOI
  125. Maheshwari A. Marks R. L. Yu K. M. Noebels J. L. (2016). Shift in interictal relative γ power as a novel biomarker for drug response in two mouse models of absence epilepsy. Epilepsia 57, 79– 88. 10.1111/epi.13265 26663261 PMC5551895 · DOI
  126. McCleery J. Cohen D. A. Sharpley A. L. (2016). Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst. Rev. 11: CD009178. 10.1002/14651858.CD009178.pub3 27851868 PMC6464889 · DOI
  127. Mebane-Sims I. Alzheimer’s Association (2009). 2009 Alzheimer’s disease facts and figures. Alzheimers Dement. 5, 234– 270. 10.1016/j.jalz.2009.03.001 19426951 · DOI
  128. Mehta D. Jackson R. Paul G. Shi J. Sabbagh M. (2017). Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010–2015. Expert Opin. Investig. Drugs 26, 735– 739. 10.1080/13543784.2017.1323868 28460541 PMC5576861 · DOI
  129. Miklossy J. Qing H. Radenovic A. Kis A. Vileno B. Làszló F.. (2010). β amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes. Neurobiol. Aging 31, 1503– 1515. 10.1016/j.neurobiolaging.2008.08.019 18950899 PMC4140193 · DOI
  130. Monroe S. M. Slavich G. M. Torres L. D. Gotlib I. H. (2007). Major life events and major chronic difficulties are differentially associated with history of major depressive episodes. J. Abnorm. Psychol. 116, 116– 124. 10.1037/0021-843X.116.1.116 17324022 PMC3631311 · DOI
  131. Monti G. Tondelli M. Giovannini G. Bedin R. Nichelli P. F. Trenti T.. (2015). Cerebrospinal fluid tau proteins in status epilepticus. Epilepsy Behav. 49, 150– 154. 10.1016/j.yebeh.2015.04.030 25958230 · DOI · Paper page
  132. Morales R. Moreno-Gonzalez I. Soto C. (2013). Cross-seeding of misfolded proteins: implications for etiology and pathogenesis of protein misfolding diseases. PLoS Pathog. 9: e1003537. 10.1371/journal.ppat.1003537 24068917 PMC3777858 · DOI
  133. Moran M. Lynch C. Walsh C. Coen R. Coakley D. Lawlor B. (2005). Sleep disturbance in mild to moderate Alzheimer’s disease. Sleep Med. 6, 347– 352. 10.1016/j.sleep.2004.12.005 15978517 · DOI
  134. Moreno-Gonzalez I. Baglietto-Vargas D. Sanchez-Varo R. Jimenez S. Trujillo-Estrada L. Sanchez-Mejias E.. (2009). Extracellular amyloid-β and cytotoxic glial activation induce significant entorhinal neuron loss in young PS1M146L/APP751SL mice. J. Alzheimers Dis. 18, 755– 776. 10.3233/JAD-2009-1192 19661615 · DOI
  135. Moreno-Gonzalez I. Edwards Iii G. Salvadores N. Shahnawaz M. Diaz-Espinoza R. Soto C. (2017). Molecular interaction between type 2 diabetes and Alzheimer’s disease through cross-seeding of protein misfolding. Mol. Psychiatry 22, 1327– 1334. 10.1038/mp.2016.230 28044060 PMC5495631 · DOI
  136. Moreno-Gonzalez I. Estrada L. D. Sanchez-Mejias E. Soto C. (2013). Smoking exacerbates amyloid pathology in a mouse model of Alzheimer’s disease. Nat. Commun. 4: 1495. 10.1038/ncomms2494 23422663 · DOI
  137. Moreno-Gonzalez I. Soto C. (2011). Misfolded protein aggregates: mechanisms, structures and potential for disease transmission. Semin. Cell Dev. Biol. 22, 482– 487. 10.1016/j.semcdb.2011.04.002 21571086 PMC3175247 · DOI · Paper page
  138. Morris M. C. Tangney C. C. Wang Y. Sacks F. M. Bennett D. A. Aggarwal N. T. (2015). MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers Dement. 11, 1007– 1014. 10.1016/j.jalz.2014.11.009 25681666 PMC4532650 · DOI · Paper page
  139. Morris J. K. Vidoni E. D. Johnson D. K. Van Sciver A. Mahnken J. D. Honea R. A.. (2017). Aerobic exercise for Alzheimer’s disease: a randomized controlled pilot trial. PLoS One 12: e0170547. 10.1371/journal.pone.0170547 28187125 PMC5302785 · DOI
  140. Mucke L. Selkoe D. J. (2012). Neurotoxicity of amyloid β-protein: synaptic and network dysfunction. Cold Spring Harb. Perspect. Med. 2: a006338. 10.1101/cshperspect.a006338 22762015 PMC3385944 · DOI · Paper page
  141. Muñoz G. Urrutia J. C. Burgos C. F. Silva V. Aguilar F. Sama M.. (2015). Low concentrations of ethanol protect against synaptotoxicity induced by Aβ in hippocampal neurons. Neurobiol. Aging 36, 845– 856. 10.1016/j.neurobiolaging.2014.10.017 25433458 · DOI
  142. Muqtadar H. Testai F. D. Gorelick P. B. (2012). The dementia of cardiac disease. Curr. Cardiol. Rep. 14, 732– 740. 10.1007/s11886-012-0304-8 22968344 · DOI
  143. Nichol K. Deeny S. P. Seif J. Camaclang K. Cotman C. W. (2009). Exercise improves cognition and hippocampal plasticity in APOE ε4 mice. Alzheimers Dement. 5, 287– 294. 10.1016/j.jalz.2009.02.006 19560099 PMC4105011 · DOI · Paper page
  144. Nichol K. E. Parachikova A. I. Cotman C. W. (2007). Three weeks of running wheel exposure improves cognitive performance in the aged Tg2576 mouse. Behav. Brain Res. 184, 124– 132. 10.1016/j.bbr.2007.06.027 17698211 PMC2215770 · DOI
  145. Nigam S. M. Xu S. Kritikou J. S. Marosi K. Brodin L. Mattson M. P. (2017). Exercise and BDNF reduce Aβ production by enhancing α-secretase processing of APP. J. Neurochem. 142, 286– 296. 10.1111/jnc.14034 28382744 PMC5498234 · DOI
  146. Nordberg A. (2015). Towards early diagnosis in Alzheimer disease. Nat. Rev. Neurol. 11, 69– 70. 10.1038/nrneurol.2014.257 25623789 · DOI
  147. Nordberg A. Hellström-Lindahl E. Lee M. Johnson M. Mousavi M. Hall R.. (2002). Chronic nicotine treatment reduces β-amyloidosis in the brain of a mouse model of Alzheimer’s disease (APPsw). J. Neurochem. 81, 655– 658. 10.1046/j.1471-4159.2002.00874.x 12065674 · DOI
  148. Nordström A. Nordström P. (2018). Traumatic brain injury and the risk of dementia diagnosis: a nationwide cohort study. PLoS Med. 15: e1002496. 10.1371/journal.pmed.1002496 29381704 PMC5790223 · DOI · Paper page
  149. Ohia-Nwoko O. Montazari S. Lau Y. S. Eriksen J. L. (2014). Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice. Mol. Neurodegener. 9: 54. 10.1186/1750-1326-9-54 25432085 PMC4280713 · DOI
  150. Omar S. H. Scott C. J. Hamlin A. S. Obied H. K. (2018). Biophenols: Enzymes (β-secretase, Cholinesterases, histone deacetylase and tyrosinase) inhibitors from olive (Olea europaea L.). Fitoterapia 128, 118– 129. 10.1016/j.fitote.2018.05.011 29772299 · DOI
  151. Ott A. Slooter A. J. Hofman A. van Harskamp F. Witteman J. C. Van Broeckhoven C.. (1998). Smoking and risk of dementia and Alzheimer’s disease in a population-based cohort study: the Rotterdam Study. Lancet 351, 1840– 1843. 10.1016/s0140-6736(97)07541-7 9652667 · DOI · Paper page
  152. Ott A. Stolk R. P. van Harskamp F. Pols H. A. Hofman A. Breteler M. M. (1999). Diabetes mellitus and the risk of dementia: the Rotterdam study. Neurology 53, 1937– 1942. 10.1212/wnl.53.9.1937 10599761 · DOI · Paper page
  153. Panpalli Ates M. Karaman Y. Guntekin S. Ergun M. A. (2016). Analysis of genetics and risk factors of Alzheimer’s disease. Neuroscience 325, 124– 131. 10.1016/j.neuroscience.2016.03.051 27026590 · DOI
  154. Parrott M. D. Winocur G. Bazinet R. P. Ma D. W. L. Greenwood C. E. (2015). Whole-food diet worsened cognitive dysfunction in an Alzheimer’s disease mouse model. Neurobiol. Aging 36, 90– 99. 10.1016/j.neurobiolaging.2014.08.013 25212462 · DOI
  155. Pendlebury S. T. Rothwell P. M. (2009). Prevalence, incidence and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol. 8, 1006– 1018. 10.1016/s1474-4422(09)70236-4 19782001 · DOI · Paper page
  156. Peng Y. Hou C. Yang Z. Li C. Jia L. Liu J.. (2016). Hydroxytyrosol mildly improve cognitive function independent of APP processing in APP/PS1 mice. Mol. Nutr. Food Res. 60, 2331– 2342. 10.1002/mnfr.201600332 27287957 · DOI
  157. Peters R. Beckett N. Forette F. Tuomilehto J. Clarke R. Ritchie C.. (2008). Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol. 7, 683– 689. 10.1016/S1474-4422(08)70143-1 18614402 · DOI · Paper page
  158. Petrovitch H. White L. R. Izmirilian G. Ross G. W. Havlik R. J. Markesbery W.. (2000). Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Neurobiol. Aging 21, 57– 62. 10.1016/s0197-4580(00)00106-8 10794849 · DOI · Paper page
  159. Plassman B. L. Havlik R. J. Steffens D. C. Helms M. J. Newman T. N. Drosdick D.. (2000). Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias. Neurology 55, 1158– 1166. 10.1212/wnl.55.8.1158 11071494 · DOI · Paper page
  160. Rabin J. S. Yang H. Schultz A. P. Hanseeuw B. J. Hedden T. Viswanathan A.. (2019). Vascular risk and β-amyloid are synergistically associated with cortical tau. Ann. Neurol. 85, 272– 279. 10.1002/ana.25399 30565287 PMC6351182 · DOI
  161. Ramos B. Baglietto-Vargas D. del Rio J. C. Moreno-Gonzalez I. Santa-Maria C. Jimenez S.. (2006). Early neuropathology of somatostatin/NPY GABAergic cells in the hippocampus of a PS1 × APP transgenic model of Alzheimer’s disease. Neurobiol. Aging 27, 1658– 1672. 10.1016/j.neurobiolaging.2005.09.022 16271420 · DOI
  162. Raschetti R. Albanese E. Vanacore N. Maggini M. (2007). Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Med. 4: e338. 10.1371/journal.pmed.0040338 18044984 PMC2082649 · DOI
  163. Rasmuson S. Andrew R. Näsman B. Seckl J. R. Walker B. R. Olsson T. (2001). Increased glucocorticoid production and altered cortisol metabolism in women with mild to moderate Alzheimer’s disease. Biol. Psychiatry 49, 547– 552. 10.1016/s0006-3223(00)01015-5 11257240 · DOI
  164. Rehm J. (2011). The risks associated with alcohol use and alcoholism. Alcohol Res. Health 34, 135– 143. 22330211 PMC3307043
  165. Reijs B. L. R. Vos S. J. B. Soininen H. Lötjonen J. Koikkalainen J. Pikkarainen M.. (2017). Association between later life lifestyle factors and Alzheimer’s disease biomarkers in non-demented individuals: a longitudinal descriptive cohort study. J. Alzheimers Dis. 60, 1387– 1395. 10.3233/JAD-170039 29036813 · DOI
  166. Reitz C. den Heijer T. van Duijn C. Hofman A. Breteler M. M. B. (2007). Relation between smoking and risk of dementia and Alzheimer disease: the Rotterdam study. Neurology 69, 998– 1005. 10.1212/01.wnl.0000271395.29695.9a 17785668 · DOI
  167. Richards M. Jarvis M. J. Thompson N. Wadsworth M. E. J. (2003). Cigarette smoking and cognitive decline in midlife: evidence from a prospective birth cohort study. Am. J. Public Health 93, 994– 998. 10.2105/ajph.93.6.994 12773367 PMC1447882 · DOI · Paper page
  168. Roberson E. D. Halabisky B. Yoo J. W. Yao J. Chin J. Yan F.. (2011). Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer’s disease. J. Neurosci. 31, 700– 711. 10.1523/jneurosci.4152-10.2011 21228179 PMC3325794 · DOI · Paper page
  169. Roh J. H. Jiang H. Finn M. B. Stewart F. R. Mahan T. E. Cirrito J. R. (2015). Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease. J. Exp. Med. 212: 121 10.1084/jem.2014178812122014c PMC4267230 25422493 · DOI
  170. Roher A. E. Esh C. Kokjohn T. A. Kalback W. Luehrs D. C. Seward J. D.. (2003). Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer’s disease. Arterioscler. Thromb. Vasc. Biol. 23, 2055– 2062. 10.1161/01.atv.0000095973.42032.44 14512367 · DOI
  171. Ross J. A. Gliebus G. Van Bockstaele E. J. (2018). Stress induced neural reorganization: a conceptual framework linking depression and Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 85, 136– 151. 10.1016/j.pnpbp.2017.08.004 28803923 PMC5809232 · DOI
  172. Russo A. Palumbo M. Aliano C. Lempereur L. Scoto G. Renis M. (2003). Red wine micronutrients as protective agents in Alzheimer-like induced insult. Life Sci. 72, 2369– 2379. 10.1016/s0024-3205(03)00123-1 12639702 · DOI
  173. Sah S. K. Lee C. Jang J.-H. Park G. H. (2017). Effect of high-fat diet on cognitive impairment in triple-transgenic mice model of Alzheimer’s disease. Biochem. Biophys. Res. Commun. 493, 731– 736. 10.1016/j.bbrc.2017.08.122 28865961 · DOI
  174. Sanchez P. E. Zhu L. Verret L. Vossel K. A. Orr A. G. Cirrito J. R.. (2012). Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model. Proc. Natl. Acad. Sci. U S A 109, E2895– E2903. 10.1073/pnas.1121081109 22869752 PMC3479491 · DOI · Paper page
  175. Scarmeas N. Luchsinger J. A. Mayeux R. Stern Y. (2007). Mediterranean diet and Alzheimer disease mortality. Neurology 69, 1084– 1093. 10.1212/01.wnl.0000277320.50685.7c 17846408 PMC2673956 · DOI
  176. Scharfman H. E. (2007). The neurobiology of epilepsy. Curr. Neurol. Neurosci. Rep. 7, 348– 354. 10.1007/s11910-007-0053-z 17618543 PMC2492886 · DOI
  177. Shakour N. Bianconi V. Pirro M. Barreto G. E. Hadizadeh F. Sahebkar A. (2019). In silico evidence of direct interaction between statins and β-amyloid. J. Cell. Biochem. 120, 4710– 4715. 10.1002/jcb.27761 30260016 · DOI
  178. Shen Y. Joachimiak A. Rich Rosner M. Tang W. J. (2006). Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature 443, 870– 874. 10.1038/nature05143 17051221 PMC3366509 · DOI
  179. Shokri-Kojori E. Wang G.-J. Wiers C. E. Demiral S. B. Guo M. Kim S. W.. (2018). β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc. Natl. Acad. Sci. U S A 115, 4483– 4488. 10.1073/pnas.1721694115 29632177 PMC5924922 · DOI · Paper page
  180. Sim Y.-J. (2014). Treadmill exercise alleviates impairment of spatial learning ability through enhancing cell proliferation in the streptozotocin-induced Alzheimer’s disease rats. J. Exerc. Rehabil. 10, 81– 88. 10.12965/jer.140102 24877042 PMC4025554 · DOI
  181. Steenland K. Karnes C. Seals R. Carnevale C. Hermida A. Levey A. (2012). Late-life depression as a risk factor for mild cognitive impairment or Alzheimer’s disease in 30 us Alzheimer’s disease centers. J. Alzheimers Dis. 31, 265– 275. 10.3233/JAD-2012-111922 22543846 PMC3729228 · DOI
  182. Sun M.-K. Hongpaisan J. Nelson T. J. Alkon D. L. (2008). Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains. Proc. Natl. Acad. Sci. U S A 105, 13620– 13625. 10.1073/pnas.0805952105 18768786 PMC2533239 · DOI
  183. Swan G. E. Lessov-Schlaggar C. N. (2007). The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol. Rev. 17, 259– 273. 10.1007/s11065-007-9035-9 17690985 · DOI
  184. Taillard J. Sagaspe P. Berthomier C. Brandewinder M. Amieva H. Dartigues J.-F.. (2019). Non-REM sleep characteristics predict early cognitive impairment in an aging population. Front. Neurol. 10: 197. 10.3389/fneur.2019.00197 30918496 PMC6424890 · DOI
  185. Taylor M. K. Sullivan D. K. Swerdlow R. H. Vidoni E. D. Morris J. K. Mahnken J. D.. (2017). A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults. Am. J. Clin. Nutr. 106, 1463– 1470. 10.3945/ajcn.117.162263 29070566 PMC5698843 · DOI
  186. Thériault P. ElAli A. Rivest S. (2016). High fat diet exacerbates Alzheimer’s disease-related pathology in APPswe/PS1 mice. Oncotarget 7, 67808– 67827. 10.18632/oncotarget.12179 27661129 PMC5356521 · DOI
  187. Toda A. Tagata Y. Nakada T. Komatsu M. Shibata N. Arai H. (2013). Changes in mini-mental state examination score in Alzheimer’s disease patients after stopping habitual drinking. Psychogeriatrics 13, 94– 98. 10.1111/psyg.12008 23909966 · DOI
  188. Toledo J. B. Arnold S. E. Raible K. Brettschneider J. Xie S. X. Grossman M.. (2013). Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 136, 2697– 2706. 10.1093/brain/awt188 23842566 PMC3858112 · DOI · Paper page
  189. Topiwala A. Allan C. L. Valkanova V. Zsoldos E. Filippini N. Sexton C.. (2017). Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ 357: j2353. 10.1136/bmj.j2353 28588063 PMC5460586 · DOI · Paper page
  190. Trichopoulou A. Kyrozis A. Rossi M. Katsoulis M. Trichopoulos D. La Vecchia C.. (2015). Mediterranean diet and cognitive decline over time in an elderly Mediterranean population. Eur. J. Nutr. 54, 1311– 1321. 10.1007/s00394-014-0811-z 25482573 · DOI
  191. Tseng B. Y. Uh J. Rossetti H. C. Cullum C. M. Diaz-Arrastia R. F. Levine B. D.. (2013). Masters athletes exhibit larger regional brain volume and better cognitive performance than sedentary older adults. J. Magn. Reson. Imaging 38, 1169– 1176. 10.1002/jmri.24085 23908143 PMC3812419 · DOI
  192. Um H. S. Kang E. B. Leem Y. H. Cho I. H. Yang C. H. Chae K. R.. (2008). Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer’s disease in an NSE/APPSw-transgenic model. Int. J. Mol. Med. 22, 529– 539. 10.3892/ijmm_00000052 18813861 · DOI
  193. Uryu K. Chen X.-H. Martinez D. Browne K. D. Johnson V. E. Graham D. I.. (2007). Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp. Neurol. 208, 185– 192. 10.1016/j.expneurol.2007.06.018 17826768 PMC3979356 · DOI · Paper page
  194. Valente T. Gella A. Fernàndez-Busquets X. Unzeta M. Durany N. (2010). Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer’s disease and diabetes mellitus. Neurobiol. Dis. 37, 67– 76. 10.1016/j.nbd.2009.09.008 19778613 · DOI
  195. Valls-Pedret C. Sala-Vila A. Serra-Mir M. Corella D. de la Torre R. Martínez-González M. Á.. (2015). Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Intern. Med. 175, 1094– 1103. 10.1001/jamainternmed.2015.1668 25961184 · DOI · Paper page
  196. van Dyck C. H. (2018). Anti-amyloid-β monoclonal antibodies for Alzheimer’s disease: pitfalls and promise. Biol. Psychiatry 83, 311– 319. 10.1016/j.biopsych.2017.08.010 28967385 PMC5767539 · DOI · Paper page
  197. Vemuri P. Lesnick T. G. Przybelski S. A. Knopman D. S. Lowe V. J. Graff-Radford J.. (2017). Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Ann. Neurol. 82, 706– 718. 10.1002/ana.25071 29023983 PMC5696029 · DOI
  198. Vetreno R. P. Crews F. T. (2018). Adolescent binge ethanol-induced loss of basal forebrain cholinergic neurons and neuroimmune activation are prevented by exercise and indomethacin. PLoS One 13: e0204500. 10.1371/journal.pone.0204500 30296276 PMC6175501 · DOI
  199. Vidoni E. D. Van Sciver A. Johnson D. K. He J. Honea R. Haines B.. (2012). A community-based approach to trials of aerobic exercise in aging and Alzheimer’s disease. Contemp. Clin. Trials 33, 1105– 1116. 10.1016/j.cct.2012.08.002 22903151 PMC3468654 · DOI
  200. Vijayan M. Reddy P. H. (2016). Stroke, vascular dementia, and Alzheimer’s disease: molecular links. J. Alzheimers Dis. 54, 427– 443. 10.3233/JAD-160527 27567871 PMC5793908 · DOI

200 of 219 shown

Cited by

Sorted by citations

Authors
Edwards III, G. A., Gamez, N., Escobedo Jr., G., Calderon, O., & Moreno-Gonzalez, I.
Affiliations
  • Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
  • The University of Texas Health Science Center at Houston (US)
ORCID
Gamez, Nazaret
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2019-06-24
Volume
11
Pages
146-146
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2019.00146
PMC
PMC6601685
OpenAlex
W2954731391
Cited by
253
References
50
Citations by year
2026: 12 · 2025: 31 · 2024: 34 · 2023: 60 · 2022: 42 · 2021: 42 · 2020: 30 · 2019: 2
FWCI
23.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Defense (AZ160106)
  • Alzheimer's Association (NIRG-394284)
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (F31NS103499)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, modifiable risk factors, lifestyle factors, health conditions, prevention, aging, sex differences, sporadic Alzheimer's disease, neurodegeneration, disease progression

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review