etiology/risk of Alzheimer's disease
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Etiology
- genetic links with Alzheimer's disease
- hypotheses
- cholinergic hypothesis (see CNS cholinergic system)
- cholinergic neurons in the nucleus basalis of Meynert & in the septum are selectively vulnerable in AD
- choline acetyltransferase & acetylcholine are decreased with moderate stage dementia
- degree of cognitive impairment may correlate with loss of cholinergic neurons & fibers
- chronic anticholinergic use may increase risk of AD[24][69]
- Free radical/oxidative stress hypothesis
- cholinergic hypothesis (see CNS cholinergic system)
- chronic psychosocial stress
- midlife psychosocial stress increases risk of dementia 25 years later[116]
- chronic stress exacerbates cognitive impairment in a rat model of Alzheimer's disease[19]
- chronic stress also impairs long-term potentiation
- toxins:
- aluminum: cerebral plaques seen in autopsy of dialysis patients using tap water for dialysis & reproducible in rabbits by infusion of aluminum are morphologically distinct from amyloid plaques seen in Alzheimer's disease & Down's syndrome
- dichlorodiphenyldichloroethylene (DDE), metabolite of pesticide dichlorodiphenyltrichloroethane (DDT) associated with increased risk of Alzheimer's disease [33[
- gingipains produced by Porphyromonas gingivalis identified in the brains of patients with Alzheimer's disease[65]
- COR388, an oral agent that inhibits gingipain proteases secreted by P gingivalis in a clinical trial[70]
- gingivitis may be a risk factor for AD[84]
- trans fats, elaidic acid
- infection:
- viral encephalitis with strongest association[122]
- Chlamydia pneumoniae & Herpes simplex type 1 found in brain tissue of patients with Alzheimer's disease[11]
- analysis by 16S rRNA Next Generation Sequencing reveals
- more bacteria found in postmortem brain of patients with Alzheimer's disease (7-fold more)[55]
- 10-fold higher ratio of Actinobacteria to Proteobacteria in postmortem brain of patients with Alzheimer's disease[55]
- most Actinobacteria identified as Propionibacterium acnes
- HHV6A & HHV7 may affect metabolism of APP in brain[60]
- HSV1 & Herpes zoster may increase risk of AD[60]
- reactivation of quiescent Herpes Simplex Virus Type 1 in brain may result in release of pro-inflammatory cytokines & beta-amyloid & phosphorylated tau accumulation[110]
- HHV6A, HHV6B, HHV7 & HSV1 found in postmortem brains of AD patients[70]
- HSV1 may be a risk factor[78]
- rare cases of transmissible Alzheimer's disease
- five children treated with human growth hormone from pituitary glands obtained from cadavers developed early dementia or biomarkers consistent with Alzheimer's disease by age 38-55 years[128]
risk factors
- aging is greatest risk factor for dementia
- for risk factors specific to AD, see predictors of Alzheimer's disease
- risk of AD has been stable or declining 2000-2024[136]
- the increasing prevalence of AD is due to the aging population[136]
- 2 apolipoprotein E4 alleles (2nd greatest risk factor) (see genetics)
- previous head trauma
- traumatic brain injury controversial[104]
- family history of dementia in a 1st degree relative
- greater risk than head trauma without loss of consciousness
- low level of education
- illiteracy associated with risk for dementia, but literacy status does not affect rate of cognitive decline[74]
- a higher level of education associated with a delayed diagnosis[18]
- family history of Down's syndrome
- olfactory impairment is an independent risk factor
- olfactory bulb & olfactory tract are effected early in Alzheimer's disease
- see olfaction & Alzheimer's disease
- hypercholesterolemia
- serum cholesterol > 250 mg/dL, in midlife[6]
- serum cholesterol, LDL cholesterol, HDL cholesterol NOT risk factors[5]
- low LDL cholesterol levels due to PCSK9 & HMGCR variants not linked to Alzheimer's disease, vascular dementia, any dementia, or Parkinson's disease[43]
- low LDL cholesterol level may diminish risk of vascular dementia
- higher apoE levels in HDL linked to lower dementia risk, but only when HDL did not contain apoC3[82]
- low plasma apoE is associated with higher risk of dementia & Alzheimer's disease independent of apoE genotype[82]
- blood pressure & cardiovascular risk factors
- hypertension (systolic BP > 160 mm Hg, in midlife)[5]
- low diastolic blood pressure in the elderly (< 70 mm Hg) associated with increased risk of AD (RR=1.92)[10]
- antihypertensive agents confer reduced risk[14][23][131]
- lowest hazzard ratio for K+ sparing diuretics (0.26)
- orthostatic hypotension[83]
- no convincing evidence that lowering blood pressure prevents the development of dementia or cognitive impairment in hypertensive elderly with no apparent prior cerebrovascular disease - Cochrane Database Syst Rev 2006[15]
- attenuation of the decline in blood pressure during sleep is associated with increased amyloid burden in the posterior cingulate gyrus & altered cerebral blood flow (see blood pressure)[37]
- vascular risk factors in middle age are associated with elevated brain amyloid deposition in later life[39]
- coronary artery disease before age 45 years[127]
- midlife hypertension associated with risk for later dementia only in women[51]
- resting heart rate > 80/min vs 60-69/min associated with increased risk for dementia (RR=1.55)[94]
- systolic blood pressure variability (RR=1.02-1.10)[121]
- calcium channel blockers may lower risk
- the same risk factors that cause atherosclerosis, are also major risk factors for late-life cognitive impairment & Alzheimer's disease[48]
- 25 g of processed-meat daily (2 strips of bacon) associated with increased risk of dementia over 8 years, independent of the APOE-4 status[88]
- multimorbidity
- multimorbidity during midlife increases risk for dementia[96]
- multimorbidity associated with 63% increased risk of dementia within 15 years[111]
- risk highest in patients with cardiovascular disease[111]
- higher plasma neurofilament associated with a 54% greater risk for all-cause dementia & a 49% greater risk for Alzheimer's dementia[77].
- hyperhomocysteinemia may be risk factor[8][9]
- diabetes mellitus 65% increased risk[4]
- hyperinsulinemia provokes increases in brain inflammation & beta amyloid[3]
- hyperglycemia is a risk factor for dementia, even at levels of plasma glucose = 115 mg/dl (HR = 1.18)[32]
- diabetes mellitus type 2 for >10 years doubles risk of dementia at age 70[90]
- peripheral neuropathy linked to higher risk of dementia (RR=1.9)[99]
- J-shaped association between plasma estradiol & dementia[34]
- anemia is a risk factor for dementia in older adults (RR=1.5)[31]
- sleep disturbance in middle age may be a risk factor[36]
- diminished REM sleep may be a risk factor[47]
- disruption of slow-wave activity leads to higher CSF A-beta & CSF tau[50] may be due to diminished glymphatic clearance
- sleep duration < 5 hours (RR=2.6) or > 10 hours (RR=1.7) per night associated with increased risk for dementia[59]
- sleep duration < 7 hours per night[91]
- similar U-shaped associations for Alzheimer's disease & vascular dementia[59]
- use of sleeping pills in later life increases risk (RR=1.5)[100]
- nightmares in middle-age or older adults[113]
- disruption of circadian rhythyms may be associated with amyloid plaque pathology prior to emergence of cognitive impairment[56]
- higher outdoor nighttime light exposure is associated with higher prevalence of Alzheimer's disease[133]
- obesity is risk factor for dementia[13]
- weight loss may preceed the onset of dementia[115]
- low body mass index is not a risk factor for AD[42]
- possibly oophorectomy prior to menopause[17]
- active smoking & heavy smoking in midlife[25][26]
- air pollution (RR=1.4) risk stronger for Alzheimer's disease than vascular dementia[63]
- particulate matter < 2.5 microns,including air pollution alters brain structure & increases risk for preclinical AD[75]
- long-term exposure to air pollution increases risk of dementia[76]
- heart failure & ischemic heart disease may enhance this risk
- stroke may be intermediate condition between exposure to air pollution & dementia[76]
- living without a partner at midlife[22]
- hospitalization &/or delirium increase risk of AD[28]
- an intensive care unit (ICU) stay double risk of AD[108]
- psychologic stress greatest risk factor according to[30]
- anxiety[21]
- late-life depression[27] may interact with beta-amyloid
- chronic pain[44]
- repetitive negative thinking[80]
- repeated rumination or worry[80]
- AD may start sooner for people with anxiety, depression[87]
- greater risk of dementia when spouse has dementia?[108]
- widows & lifelong singles tend to be underdiagnosed[53]
- loneliness 45-64 years of age persisting after age 65 (RR=1.9)[89]
- loneliness triples risk of dementia & is associated with worse neurocognitive markers of Alzheimer's disease & related dementia vulnerability[97]
- marriage confers lower risk for dementia[53]
- social isolation increases risk of dementia (RR=1.3)[119]
- apathy is a risk factor[61]
- benzodiazepine use in the elderly
- new benzodiazepine use in the elderly[29]
- > 180 days of use RR=1.7[29]
- antidepressant use[41] (RR=3.3-4.9)
- anticonvulsant use[58] (RR=1.15-1.3)
- androgen deprivation therapy may be associated with increased risk for AD[38]
- menopausal hormone replacement therapy increases risk of AD (RR=1.2)[124]
- chronic anticholinergic use may increase risk of AD[24][69]
- hypermagnesemia & hypomagnesemia appear to be risk factors[49]
- diminished retinal nerve fiber layer thickness on retinal optical coherence tomography linked to cognitive decline & dementia[64]
- autoimmunity may be a modifiable component in diseases associated with dementia[98]
- inflammatory disorders appear to increase risk & TNF-alpha inhibitors appear to mitigate that risk
- inflammatory bowel disease is a risk factor (RR > 2)[81]
- breakdown of the blood-brain barrier may provide entry for components of autoimmune processes[98]
- intestinal microbiota proinflammatory genus Collinsella, identified as a risk factor for AD positively correlating with the APOE rs429358 risk allele[129]
- hospitalization with infection associated with increased risk for dementia[118]
- gout is associated with a diminished risk of AD (RR=0.73-0.76)
- uric acid may be neuroprotective[35]
- gout increases risk for vascular dementia (RR=2.3)
- vitiligo (RR=12.2)[85] & alopecia areata (RR=3)[95]
- frailty is a risk factor for mild cognitive impairment & dementia[86]
- sensory impairment
- visual impairment is a potentially modifiable risk factor[101]
- hearing impairment is a potentially modifiable risk factor (see hearing loss)
- link between ADHD & Alzheimer's disease[93]
- nonalcoholic fatty liver disease (RR=1.4)[106]
- hypothyroidism requiring levothyroxine replacement therapy (RR=3)[107]
- common vaccinations (especially influenza virus vaccine & pneumococcal vaccine) may increase risk of dementia in elderly after a 2-year lag period (RR=1.4)[123]
- most consistent associations at all time points over a 15-year span include
- depression, erectile dysfunction, gait abnormalities, hearing loss, & nervous & musculoskeletal symptoms[117]
- nose picking associated with increased risk[12]
modifiable risk factors
- midlife obesity[102]
- midlife hypertension
- physical inactivity
- depression
- smoking
- low education
- diabetes mellitus
- hearing loss[102]
- visual impairment[101]
- diet
- ultraprocessed foods associated with increased risk for dementia[112]
protective factors
- genetically proxied lean mass is associated with a reduced risk of Alzheimer's disease[125]
- multiple sclerosis is associated with reduced plasma amyloid-beta & reduced Alzheimer disease risk[134]
risk factors for amyloid & tau deposition
- risk factors for amyloid deposition & neurodegeneration appear to be distinct[40]
- maternal history (at any age) & paternal history of early-onset memory impairment are associated with beta-amyloid burden among asymptomatic elderly[130]
- midlife dyslipidemia is associated with amyloid deposition
- midlife obesity, smoking, diabetes, hypertension, cardiovascular disease & metabolic disease associated with neurodegeneration[40]
- intellectual activity does not predict of amyloid deposition or neurodegeneration[40]
- elevation in baseline brain amyloid in cognitively normal persons associated with higher likelihood of later cognitive decline, although of uncertain clinical significance (median follow-up = 3.1 years)[45]
- higher plasma amyloid-beta42 associated with 40% decreased risk for AD[77]
- repetitive negative thinking linked to amyloid deposisition & entorhinal cortex tau deposits[80]
- greater depressive symptoms over time are associated with amyloid accumulation in regions associated with emotional control (medial orbitofrontal cortex, isthmus cingulate cortex & middle frontal cortex) independent of cognitive function[132]
- service in the U.S. military
- associated with post mortem neuritic amyloid plaque & tau pathology[126]
plasma proteins linked to increased risk of cognitive impairment
- proteins that inhibit central nervous system axonogenesis & synaptogenesis
- SLIT2, CHST12, PAM[92]
not risk factors
- proton pump inhibitors not a risk factor[46][52]
- controversial, some data suggests a link[103]
- alcohol consumption 1-7 drinks weekly not associated with risk of dementia (lowest risk)
- abstinence or more associated with higher risk[62]
- midlife diet does not appear to be a risk factor[67]
- physical inactivity[68] (controversial[102]
Radiology
- cerebral abnormalities on neuroimaging in older adults & in midlife are associated with an increased risk for dementia[66]
- MRI brain perivascular spaces may be proxy measure of cerebral small vessel disease, glymphatic dysfunction & risk of dementia[114]
Comparative biology
- in a triple transgenic mouse model of Alzheimer's disease canola oil increased in body weight, impaired working memory, decreased post-synaptic density protein-95 (marker of synaptic integrity), & increased the ratio of insoluble Abeta42/Abeta40[54]
- pericyte dysfunction may initiate leukoaraiosis prior to neuronal loss[57]
- in 3xTg-AD mice, Klebsiella pneumoniae can translocate from the gut to the bloodstream by penetrating the gut epithelial barrier & susequently infiltrate the brain by penetrating the blood-brain barrier[135]
Notes
Also see:
- prevention of Alzheimer's disease
- investigational therapies for AD
- causes of dementia
- risk factors for dementia
* risk factors for Alzheimer's disease vs dementia in general are not well differentiated, largely because the literature does not always distinguish the two
More general terms
Additional terms
- Alzheimer's disease (AD)
- olfaction & Alzheimer's disease
- predictors of Alzheimer's disease
- prevention of Alzheimer's disease/dementia
- risk factors & protective factors for vascular dementia
References
- ↑ Greenfield's Neuropathology, 5th ed., 1992 p.1327
- ↑ Selkoe D. Biochemistry of Alzheimer's Disease, In: Basic Neurochemistry, 5th ed, Siegel et al (eds), Raven Press, New York, 1994
- ↑ 3.0 3.1 Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, Cook DG, Peskind ER, Baker LD, Goldgaber D, Nie W, Asthana S, Plymate SR, Schwartz MW, Craft S. Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Arch Neurol. 2005 Oct;62(10):1539-44. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/16216936 <Internet> http://archneur.ama-assn.org/cgi/content/short/62/10/1539
- ↑ 4.0 4.1 Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004 May;61(5):661-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15148141
- ↑ 5.0 5.1 5.2 Journal Watch 23(12):93, 2003 Tan ZS, Seshadri S, Beiser A, Wilson PW, Kiel DP, Tocco M, D'Agostino RB, Wolf PA. Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study. Arch Intern Med. 2003 May 12;163(9):1053-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12742802
George J Elevated Blood Pressure at Age 50 Tied to Dementia Later. Mild hypertension may increase risk, even without cardiovascular disease. MedPage Today. June 13, 2018 https://www.medpagetoday.com/neurology/dementia/73469
Abell J, Kivimaki M, Dugravot A et al Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration and threshold used to define hypertension. Eur Heart J 2018. June 12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29901708 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehy288/5032485 - ↑ 6.0 6.1 Journal Watch 21(15):125, 2001 Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ. 2001 Jun 16;322(7300):1447-51. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11408299
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 15, 18. American College of Physicians, Philadelphia 2009, 2018.
- ↑ 8.0 8.1 Journal Watch 22(7):56-57, 2002 Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11844848
- ↑ 9.0 9.1 Prescriber's Letter 9(4):22 2002
- ↑ 10.0 10.1 Journal Watch 24(3):23, 2004 Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ. Low blood pressure and the risk of dementia in very old individuals. Neurology. 2003 Dec 23;61(12):1667-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14694027
- ↑ 11.0 11.1 United Press International http://www.nlm.nih.gov/medlineplus/news/fullstory_18334.html
- ↑ 12.0 12.1 Cole GM Mechanisms of prevention of Alzheimer's pathogenesis with the turmeric extract, cucurmin, and the omega-3 fatty acid, DHA Aging: Mechanisms and Prevention 34th Annual Meeting of the American Aging Association June 3-6, 2005, Oakland CA
Zhou X, Kumar P, Bhuyab DJ et al Neuroinflammation in Alzheimer's Disease: A Potential Role of Nose-Picking in Pathogen Entry via the Olfactory System? Biomolecules. 2023 Oct 24;13(11):1568. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38002250 PMCID: PMC10669446 Free PMC article - ↑ 13.0 13.1 Journal Watch 25(15):119, 2005 Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr, Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ. 2005 Jun 11;330(7504):1360. Epub 2005 Apr 29. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15863436 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7504/1360
- ↑ 14.0 14.1 Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, Tschanz JT, Mayer LS, Welsh-Bohmer KA, Breitner JC. Antihypertensive Medication Use and Incident Alzheimer Disease: The Cache County Study. Arch Neurol. 2006 Mar 13; [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/16533956
- ↑ 15.0 15.1 McGuinness B, Todd S, Passmore P, Bullock R. The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004034. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16625595
- ↑ Drachman DA Aging of the brain, entropy, and Alzheimer's disease. Neurology 2006, 67:1340 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17060558
- ↑ 17.0 17.1 Rocca WA et al, Increased risk of cognitive impairment of dementia in women who underwent oophorectomy before menopause. Neurology 2007, 69:1074 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17761551
- ↑ 18.0 18.1 Hall CB et al, Education delays accelerated decline on memory test in persons who develop dementia. Neurology 2007, 69:1657 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17954781
- ↑ 19.0 19.1 Srivareerat M et al. Chronic psychosocial stress exacerbates impairment of cognition and long-term potentiation in beta-amyloid rat model of Alzheimer's disease. Biol Psychiatry 2009 Jun 1; 65:918. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18849021
Alberini CM. Unwind: Chronic stress exacerbates the deficits of Alzheimer's disease. Biol Psychiatry 2009 Jun 1; 65:916. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19433151 - ↑ Hakansson K et al Association between mid-life marital status and cognitive function in later life: population based cohort study BMJ 2009;339:b2462 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19574312
Helmer C Dementia and marital status at midlife and late life. BMJ 2009;339:b1690 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19574311 - ↑ 21.0 21.1 Gallacher J et al Does anxiety affect risk of dementia? Findings from the Caerphilly Prospective Study. Psychosom Med 2009 Jul; 71:659 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19553290
- ↑ 22.0 22.1 Hakansson K et al Association between mid-life marital status and cognitive function in later life: Population based cohort study. BMJ 2009 Jul 2; 339:b2462. http://dx.doi.org/10.1136/bmj.b2462 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19574312
- ↑ 23.0 23.1 Hoffman LB et al. Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons. Neurology 2009 May 19; 72:1720. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19228583
Haag MDM et al Duration of antihypertensive drug use and risk of dementia: A prospective cohort study. Neurology 2009 May 19; 72:1727. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19228584 - ↑ 24.0 24.1 24.2 Carriere I et al Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-city study. Arch Intern Med 2009 Jul 27; 169:1317. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19636034
- ↑ 25.0 25.1 Rusanen M et al Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia Arch Intern Med. Published online October 25, 2010. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20975015 doi:10.1001/archinternmed.2010.393 http://archinte.ama-assn.org/cgi/content/short/archinternmed.2010.393
- ↑ 26.0 26.1 Daviglus ML, Bell CC, Berretini W, et al. National Institutes of Health State-of-the-Science Conference statement: Preventing Alzheimer disease and cognitive decline. Ann Intern Med 2010; 153:176-181. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20547888
- ↑ 27.0 27.1 Bai F et al. Topologically convergent and divergent structural connectivity patterns between patients with remitted geriatric depression and amnestic mild cognitive impairment. J Neurosci 2012 Mar 21; 32:4307 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22442092
Xu W et al. Amyloid pathologies modulate the associations of minimal depressive symptoms with cognitive impairments in older adults without dementia. Biol Psychiatry 2020 Jul 14; [e-pub] Not indexed in PubMed https://www.biologicalpsychiatryjournal.com/article/S0006-3223(20)31742-X/fulltext - ↑ 28.0 28.1 Fong TG et al Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease Ann Intern Med. 19 June 2012;156(12):848-856 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22711077 <Internet> http://annals.org/article.aspx?articleid=1183010
- ↑ 29.0 29.1 29.2 Billioti de Gage S et al Benzodiazepine use and risk of dementia: prospective population based study BMJ 2012;345:e6231 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23045258 <Internet> http://www.bmj.com/content/345/bmj.e6231
Gallacher J et al Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS). J Epidemiol Community Health. 2012 Oct;66(10):869-73 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22034632
Billioti de Gage S et al. Benzodiazepine use and risk of Alzheimer's disease: Case- control study. BMJ 2014 Sep 9; 349:g5205 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25208536 - ↑ 30.0 30.1 30.2 Russ TC, Hamer M, Stamatakis E, et al. Psychological distress as a risk factor for dementia death. Arch Intern Med 2011; 171(20):1858-1859 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22083575
- ↑ 31.0 31.1 Hong CH, Falvey C, Harris TB et al Anemia and risk of dementia in older adults Neurology. July 31, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23902706 <Internet> http://www.neurology.org/content/early/2013/07/31/WNL.0b013e31829e701d.short
- ↑ 32.0 32.1 Crane PK et al Glucose Levels and Risk of Dementia. N Engl J Med 2013; 369:540-548August 8, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23924004 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1215740
- ↑ Richardson JR et al Elevated Serum Pesticide Levels and Risk for Alzheimer Disease. JAMA Neurol. Published online January 27, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24473795 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=1816015
DeKosky ST and Gandy S Environmental Exposures and the Risk for Alzheimer Disease. Can We Identify the Smoking Guns? JAMA Neurol. Published online January 27, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24473699 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=1816013 - ↑ 34.0 34.1 Carcaillon L et al High plasma estradiol interacts with diabetes on risk of dementia in older postmenopausal women. Neurology. January 29, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24477111 <Internet> http://www.neurology.org/content/early/2014/01/29/WNL.0000000000000107.abstract
- ↑ 35.0 35.1 Lu N et al. Gout and the risk of Alzheimer's disease: A population-based, BMI-matched cohort study. Ann Rheum Dis 2015 Mar 4 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25739830 <Internet> http://ard.bmj.com/content/early/2015/02/11/annrheumdis-2014-206917
Gever J Is Gout Protective Against Dementia? Provocative results from Korean study. MedPage Today May 25, 2022 https://www.medpagetoday.com/rheumatology/generalrheumatology/98910
Kim JH, Yim DK, Choi IA et al The impact of clinical association between gout and dementia: a nationwide population-based cohort study in Korea. Arthritis Car & Research 2022. May 23 https://onlinelibrary.wiley.com/doi/abs/10.1002/acr.24959 - ↑ 36.0 36.1 Sprecher KE, Bendlin BB, Racine AM et al Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults. Neurobiol Aging. 2015 Sep;36(9):2568-76. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26059712
- ↑ 37.0 37.1 Tarumi T et al. Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment. Neurology 2015 Dec 1; 85:1922 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26537049
- ↑ 38.0 38.1 Nead KT et al. Androgen deprivation therapy and future Alzheimer's disease risk. J Clin Oncol 2016 Feb 20; 34:566. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26644522 Free Article <Internet> http://jco.ascopubs.org/content/34/6/566
McGinty HL. Unlocking electronic medical record data to identify possible connections between cancer and cognitive declines. J Clin Oncol 2016 Feb 20; 34:530. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26712232 Free Article <Internet> http://jco.ascopubs.org/content/34/6/530 - ↑ 39.0 39.1 Gottesman RF, Schneider AL, Zhou Y et al Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition. JAMA. 2017;317(14):1443-1450 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28399252 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2616396
- ↑ 40.0 40.1 40.2 40.3 Jenkins K Different Risks for Amyloid, Neurodegeneration - In Alzheimer's, risk factors for two disease hallmarks are distinct. MedPage Today. April 17, 2017 https://www.medpagetoday.com/Neurology/AlzheimersDisease/64601
Vemuri P et al Evaluation of amyloid protective factors and Alzheimer disease neurodegeneration protective factors in elderly individuals JAMA Neurol. 2017 Apr 17 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28418521 - ↑ 41.0 41.1 Then CK et al. Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan. PLoS One 2017 Apr 6; 12:e0175187 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28384235 Free Article
- ↑ 42.0 42.1 Nordestgaard LT, Tybjaerg-Hansen A, Nordestgaard BG et al Body Mass Index and Risk of Alzheimer Disease: a Mendelian Randomization Study of 399,536 Individuals. J Clin Endocrinol Metab jc.2017-00195. May 9, 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28609829 https://academic.oup.com/jcem/article-abstract/doi/10.1210/jc.2017-00195/3805501/Body-Mass-Index-and-Risk-of-Alzheimer-Disease-a?redirectedFrom=fulltext
- ↑ 43.0 43.1 Benn M et al. Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's disease and Parkinson's disease: Mendelian randomisation study. BMJ 2017 Apr 24; 357:j1648 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28438747 Free PMC Article
- ↑ 44.0 44.1 Whitlock EL, Diaz-Ramirez LG, Glymour MM et al Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders. JAMA Intern Med. Published online June 5, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28586818 <Internet> http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2629448
- ↑ 45.0 45.1 Donohue MC, Sperling RA, Petersen R et al Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons. JAMA. 2017;317(22):2305-2316 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28609533 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2631529
Visser PJ, Tijms B. Brain Amyloid Pathology and Cognitive Function. Alzheimer Disease Without Dementia. JAMA. 2017;317(22):2285-2287 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28609518 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2631513 - ↑ 46.0 46.1 Taipale H, Tolppanen AM, Tiihonen M et al. No association between proton pump inhibitor use and risk of Alzheimer's disease. Am J Gastroenterol 2017 Jul 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28695906
- ↑ 47.0 47.1 Pase MP, Himali JJ, Grima NA et al Sleep architecture and the risk of incident dementia in the community Neurology 2017; 89:1-7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28835407
- ↑ 48.0 48.1 Gorelick PB, Furie KL, Iadecola C et al Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association. Stroke. Sept 7, 2017 http://stroke.ahajournals.org/content/early/2017/09/07/STR.0000000000000148
- ↑ 49.0 49.1 Kieboom BCT, Licher S, Wolters FJ et al Serum magnesium is associated with the risk of dementia. Neurol 2017; 89(1-7). PMID: https://www.ncbi.nlm.nih.gov/pubmed/28931641
- ↑ 50.0 50.1 Ju YS, Ooms SJ, Sutphen C, et al. Slow wave sleep disruption increases cerebrospinal fluid amyloid-beta levels. Brain 2017 Aug; 140:2104 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28899014
- ↑ 51.0 51.1 Gilsanz P, Mayeda ER, Glymour M et al Female sex, early-onset hypertension, and risk of dementia. Neurology. October 4, 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28978656 <Internet> http://www.neurology.org/content/early/2017/10/04/WNL.0000000000004602
- ↑ 52.0 52.1 Goldstein FC, Steenland K, Zhao L et al Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc 2017 Sep; 65:1969-1974 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28590010
- ↑ 53.0 53.1 53.2 Kneisel K. Married Folks Seem to Have Lower Dementia Risk. Widowed, lifelong singles tend to be underdiagnosed in routine clinical practice. MedPage Today Nov 28, 2017 https://www.medpagetoday.com/geriatrics/dementia/69529
Sommerlad A, Ruegger J, Singh-Manoux A, Lewis G, Livingston G. Marriage and risk of dementia: systematic review and meta- analysis of observational studies. J Neurol Neurosurg Psychiatry 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29183958
Chen CPLH, Mok VCT. Marriage and risk of dementia: systematic review and meta- analysis of observational studies. J Neurol Neurosurg Psychiatry 2017 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29183957 Free Article - ↑ 54.0 54.1 Lauretti E, Pratico D Effect of canola oil consumption on memory, synapse and neuropathology in the triple transgenic mouse model of Alzheimer's disease. Scientific Reports 7, Article number: 17134 (Dec 7, 2017) PMID: https://www.ncbi.nlm.nih.gov/pubmed/29215028 Free PMC Article https://www.nature.com/articles/s41598-017-17373-3
- ↑ 55.0 55.1 55.2 Emery DC, Shoemark DK, Batstone TE et al 16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain. Front Aging Neurosci. 2017 Jun 20;9:195. eCollection 2017. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28676754 Free PMC Article
- ↑ 56.0 56.1 George J, Circadian Dysfunction May ID Preclinical Alzheimer's. Fragmented rhythms associated with plaque pathology. MedPage Today. January 29, 2018 https://www.medpagetoday.com/neurology/alzheimersdisease/70815
Musiek E et al Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease. JAMA Neurology 2018;
Musiek ES. Circadian Rhythms in AD pathogenesis: A Critical Appraisal. Curr Sleep Med Rep. 2017 Jun;3(2):85-92. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29308355
Musiek ES, Holtzman DM. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science. 2016 Nov 25;354(6315):1004-1008. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27885006 Free PMC Article - ↑ 57.0 57.1 Montagne A, Nikolakopoulou AM, Zhao Z et al Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. Nature Medicine Feb 5, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29400711 https://www.nature.com/articles/nm.4482
- ↑ 58.0 58.1 University of Eastern Finland Antiepileptic drugs increase risk of Alzheimer's and dementia. Science News. April 9, 2018 https://www.sciencedaily.com/releases/2018/04/180409103901.htm
- ↑ 59.0 59.1 59.2 Ohara T, Honda T Hata J et al. Association Between Daily Sleep Duration and Risk of Dementia and Mortality in a Japanese Community. J Am Geriatr Soc. June 6, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29873398
- ↑ 60.0 60.1 60.2 Readhead B, Haure-Mirande JV, Funk CC et al Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron. June 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29937276 https://www.cell.com/neuron/fulltext/S0896-6273(18)30421-5
Eimer WA, Vijaya Kumar DK et al. Alzheimer's disease-associated beta-amyloid is rapidly seeded by Herpesviridae to protect against brain infection. Neuron 2018 Jul 11; 99:56. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30001512 https://www.cell.com/neuron/fulltext/S0896-6273(18)30526-9
Itzhaki RF, Lathe R. Herpes viruses and senile dementia: First population evidence for a causal link. J Alzheimers Dis 2018; 64:363. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29889070 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad180266 - ↑ 61.0 61.1 Monaco K Apathy Tied to Higher Dementia Risk in Memory Clinic Patients. Findings suggest early marker for clinically significant cognitive decline. MedPage Today. July 18, 2018 https://www.medpagetoday.com/geriatrics/dementia/74088
Willem van Dalen J, van Wanrooij LL, Moll van Charante EP et al Association of apathy with risk of incident dementia: A Systematic Review and Meta-analysis. JAMA Psychiatry, July 18, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30027214 - ↑ 62.0 62.1 Sabia S, Fayosse A, Dumurgier J et al Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ 2018;362:k2927 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30068508 Free full text https://www.bmj.com/content/362/bmj.k2927
Yasar S Relation between alcohol consumption in midlife and dementia in late life. BMJ 2018;362:k3164 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30068510 https://www.bmj.com/content/362/bmj.k3164https://www.bmj.com/content/362/bmj.k3164 - ↑ 63.0 63.1 Carey IM, Anderson HR, Atkinson RW et al Are noise and air pollution related to the incidence of dementia? A cohort study in London, England BMJ Open. 2018. 8(9) https://bmjopen.bmj.com/content/8/9/e022404
- ↑ 64.0 64.1 Mutlu U, Colijn JM, Ikram MA et al. Association of retinal neurodegeneration on optical coherence tomography with dementia: A population-based study. JAMA Neurol 2018 Oct 1; 75:1256. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29946702 https://jamanetwork.com/journals/jamaneurology/article-abstract/2685868
Ko F, Muthy ZA, Gallacher J et al. Association of retinal nerve fiber layer thinning with current and future cognitive decline: A study using optical coherence tomography. JAMA Neurol 2018 Oct 1; 75:1198 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29946685 https://jamanetwork.com/journals/jamaneurology/article-abstract/2685869 - ↑ 65.0 65.1 Dominy SS, Lynch C, Ermini F et al Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances 23 Jan 2019: Vol. 5, no. 1, eaau3333 http://advances.sciencemag.org/content/5/1/eaau3333.full
- ↑ 66.0 66.1 West NA, Windham G, Knopman DS et al. Neuroimaging findings in midlife and risk of late-life dementia over 20 years of follow-up. Neurology 2019 Jan 18 https://n.neurology.org/content/92/9/e917
- ↑ 67.0 67.1 Akbaraly TN, Singh-Manoux A, Dugravot A et al Association of Midlife Diet With Subsequent Risk for Dementia. JAMA. 2019;321(10):957-968. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30860560 https://jamanetwork.com/journals/jama/fullarticle/2727449
- ↑ 68.0 68.1 Kivimaki M, Singh-Manoux A, Pentti J et al Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis. BMJ 2019;365:l1495 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30995986 Free Article https://www.bmj.com/content/365/bmj.l1495
- ↑ 69.0 69.1 69.2 Coupland CAC, Hill T, Dening T et al Anticholinergic Drug Exposure and the Risk of Dementia. A Nested Case-Control Study. JAMA Intern Med. Published online June 24, 2019. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31233095 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2736353
Campbell NL, Holden R, Boustani MA et al. Preventing Alzheimer disease by deprescribing anticholinergic medications. JAMA Intern Med 2019 Jun 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31233087 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2736349 - ↑ 70.0 70.1 70.2 George J Does Alzheimer's Disease Stem From Infection? Scientists debate, and one company targets gingivitis bacterium to slow Alzheimer's progression. MedPage Today. July 17, 2019 https://www.medpagetoday.com/meetingcoverage/aaic/81065
Weninger S, et al Emerging Concepts in Basic Science Series: Is There a Causative Role for Infectious Organisms in Alzheimer's Disease. Alzheimer's Association International Conference (AAIC) 2019.
Detke M, et al Initiation of the Phase 2/3 GAIN trial of COR388, a novel bacterial virulence factor inhibitor for the treatment of Alzheimer's Disease (AD) based on Phase I a/b safety, PK, biomarker and efficacy data. Alzheimer's Association International Conference (AAIC) 2019 abstract P4-663. - ↑ Brower V Anti-TNF Drugs May Reduce Risk of Alzheimer's - Large analysis indicates elevated risk with inflammatory diseases, reduced risk with TNF blockers MedPage Today October 9, 2019 (reference deprecated)
Zhou M et al Tumor necrosis factor (TNF) blocking agents reduce risk for Alzheimer's disease in patients with rheumatoid arthritis and psoriasis. medRxiv 2019; (not indexed in PubMed) - ↑ George J Dementia Tied to Trans Fats - Study links all-cause dementia and Alzheimer's to higher blood levels of elaidic acid MedPage Today. October 24, 2019 https://www.medpagetoday.com/neurology/dementia/82917
Honda T, Ohara T, Shinohara M et al Serum elaidic acid concentration and risk of dementia. The Hisayama study. Neurology 2019. Oct 23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31645469 - ↑ Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
- ↑ 74.0 74.1 George J Illiteracy Tied to Dementia Risk - But literacy status did not affect the rate of cognitive decline. MedPage Today. November 13, 2019 https://www.medpagetoday.com/neurology/dementia/83321
Arce Renteria M, Vonk JMJ et al Illiteracy, dementia risk, and cognitive trajectories among older adults with low education. Neurology. Nov 13, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31722961 https://n.neurology.org/content/early/2019/11/12/WNL.0000000000008587 - ↑ 75.0 75.1 Younan D, Petkus AJ, Widaman KF et al Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer's disease. Brain. Nov 20, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31746986 https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awz348/5628036?redirectedFrom=fulltext
- ↑ 76.0 76.1 76.2 Grande G, Ljungman PLS, Eneroth k et al Association Between Cardiovascular Disease and Long-term Exposure to Air Pollution With the Risk of Dementia. JAMA Neurol. Published online March 30, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32227140 Free PMC Article https://jamanetwork.com/journals/jamaneurology/fullarticle/2763459
- ↑ 77.0 77.1 77.2 de Wolf F, Ghanbari M, Licher S et al. Plasma tau, neurofilament light chain and amyloid-beta levels and risk of dementia; a population-based cohort study. Brain 2020 Apr 1; 143:1220 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32206776 Free PMC Article https://academic.oup.com/brain/article/143/4/1220/5811096
- ↑ 78.0 78.1 Cairns DM, Rouleau N, Parker RN et al. A 3D human brain-like tissue model of herpes-induced Alzheimer's disease. Sci Adv 2020 May 6; 6:eaay8828. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32494701 Free PMC article. https://advances.sciencemag.org/content/6/19/eaay8828
- ↑ Komaroff AL Can Infections Cause Alzheimer Disease? JAMA. Published online June 8, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32511670 https://jamanetwork.com/journals/jama/fullarticle/2767210
- ↑ 80.0 80.1 80.2 80.3 George J Repetitive Negative Thinking Linked With Alzheimer's - Rumination, worry tied to amyloid, tau, and cognitive decline. MedPage Today June 8, 2020 https://www.medpagetoday.com/neurology/alzheimersdisease/86953
Marchant NL, Lovland LR, Jones R et al Repetitive negative thinking is associated with amyloid, tau, and cognitive decline. Alzheimer's & DEmentia, June 7, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32508019 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12116 - ↑ 81.0 81.1 Zhang B, Wang HF, Bai YM et al Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study , Gut (BMJ Journal) ePub June 24, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32576641 https://gut.bmj.com/content/early/2020/04/28/gutjnl-2020-320789
- ↑ 82.0 82.1 82.2 George J HDL Protein Linked to Lower Dementia Risk - Findings extend associations from cardiovascular disease to dementia. MedPage Today July 14, 2020 https://www.medpagetoday.com/neurology/dementia/87564
Koch M, DeKosky ST, Goodman M et al Association of Apolipoprotein E in Lipoprotein Subspecies With Risk of Dementia. JAMA Netw Open. 2020;3(7):e209250. July 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32648923 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768103
Thambisetty,M Plasma Apolipoprotein E Levels and Risk of Dementia - You Are the Company You Keep JAMA Netw Open. 2020;3(7):e209501 July 10 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32648920 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768100 - ↑ 83.0 83.1 George J Ten Targets for Reducing Alzheimer's Risk - Meta-analysis offers evidence-based guidance for Alzheimer's prevention. MedPage Today July 21, 2020 https://www.medpagetoday.com/neurology/alzheimersdisease/87674
Yu JT, Xu W, Tan CC et al vidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials J Neurol, Neurosurg Psychiatry. 2020 (online July) PMID: https://www.ncbi.nlm.nih.gov/pubmed/32690803 https://jnnp.bmj.com/content/early/2020/06/01/jnnp-2019-321913 - ↑ 84.0 84.1 Demmer RT, Norby FL, Lakshminarayan K Periodontal Disease and Incident Dementia: The Atherosclerosis Risk in Communities Study (ARIC). Neurology. July 29 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32727837 https://n.neurology.org/content/early/2020/07/29/WNL.0000000000010312
- ↑ 85.0 85.1 Chang TH, Tai TH, Dai YX et al Association between vitiligo and subsequent risk of dementia: A population-based cohort study. J Dermatol. 2020. Nov 12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33180352 https://onlinelibrary.wiley.com/doi/abs/10.1111/1346-8138.15582
- ↑ 86.0 86.1 Meglio M Health-Deficit Accumulation Affects Risk for Mild Cognitive Impairment, Dementia. NeurologyLive. 2020. Nov 17. https://www.neurologylive.com/view/health-deficit-accumulation-affects-chance-of-mild-cognitive-impairment-dementia
- ↑ 87.0 87.1 George J Alzheimer's May Start Sooner for People With Anxiety, Depression History - Psychiatric disorders could have additive effects on AD pathophysiology, study suggests. MedPage Today February 24, 2021 https://www.medpagetoday.com/meetingcoverage/aan/91346
- ↑ 88.0 88.1 Zhang H, Greenwood DC, Risch HA et al Meat consumption and risk of incident dementia: cohort study of 493,888 UK Biobank participants. Am J Clin Nutr 2021. March 22 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33748832 https://academic.oup.com/ajcn/advance-article-abstract/doi/10.1093/ajcn/nqab028/6178922
- ↑ 89.0 89.1 George J Middle-Age Loneliness Linked to Alzheimer's Disease. Relationship varied, depending on whether loneliness persisted. MedPage Today March 25, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/91811
Akhter-Khan SC, et al Associations of loneliness with risk of Alzheimer's disease dementia in the Framingham Heart Study. Alzheimer's Dement 2021. March 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33760348 https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.12327 - ↑ 90.0 90.1 Barbiellini Amidei C et al. Association between age at diabetes onset and subsequent risk of dementia. JAMA 2021 Apr 27; 325:1640. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33904867 https://jamanetwork.com/journals/jama/article-abstract/2779197
- ↑ 91.0 91.1 Sabia S et al. Association of sleep duration in middle and old age with incidence of dementia. Nat Commun 2021 Apr 20; 12:2289. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33879784 PMCID: PMC8058039 Free PMC article https://www.nature.com/articles/s41467-021-22354-2
- ↑ 92.0 92.1 Kivimaki M et al. Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: Three analyses of population cohort studies. BMJ 2021 Aug 18; 374:n1804 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34407988 PMCID: PMC8372196 Free PMC article https://www.bmj.com/content/374/bmj.n1804
- ↑ 93.0 93.1 Brooks M ADHD a New Risk Factor for Alzheimer's? Medscape. September 15, 2021 https://www.medscape.com/viewarticle/958784
- ↑ 94.0 94.1 George J Dementia Tied to Resting Heart Rate. Findings persist even after accounting for cardiovascular disease. MedPage Today December 3, 2021 https://www.medpagetoday.com/neurology/dementia/95999
Imahori Y, Vetrano DL, Xia X et al Association of resting heart rate with cognitive decline and dementia in older adults: A population-based cohort study. Alzheimer's & Dementia. Dec 3, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34859936 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12495 - ↑ Swift Yasgur B Alopecia Tied to a Threefold Increased Risk for Dementia. Medscape. November 3, 2021 https://www.medscape.com/viewarticle/962186
- ↑ 96.0 96.1 George J Midlife Conditions Linked With Later Dementia Early onset of two or more chronic diseases ups dementia risk. MedPage Today February 2, 2022 https://www.medpagetoday.com/neurology/dementia/96990
Ben Hassen C, Fayosse A, Landre B et al Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study. BMJ 2022;376:e068005 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35110302 Free article https://www.bmj.com/content/376/bmj-2021-068005 - ↑ 97.0 97.1 George J Loneliness May Triple Dementia Risk. Even without dementia, lonely feelings linked with brain changes. MedPage Today February 9, 2022 https://www.medpagetoday.com/neurology/dementia/97105
Salinas J, Beiser AS, Samra JK et al Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline. Neurology 2022. February 07 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35131906 https://n.neurology.org/content/early/2022/02/07/WNL.0000000000200039 - ↑ 98.0 98.1 98.2 Ghanjanasak T Causal Evidence for Autoimmunity in Dementia? Medscape. Feb 28, 2022 https://www.medscape.com/viewarticle/969346
Lindbolm JV, Mars N, Sipila PN et al Immune system and blood-brain barrier-wide biomarker analyses provide causal evidence for autoimmunity in dementia. MedRxiv. 2022. Feb 18. https://www.medrxiv.org/content/10.1101/2022.02.17.22271136v1 - ↑ 99.0 99.1 George J Peripheral Nerve Problems Tied to Later Dementia. Findings may indicate shared susceptibility to neurodegeneration. MedPage Today March 11, 2022 https://www.medpagetoday.com/neurology/dementia/97632
Brenowitz WD, Robbins NM, Strotmeyer ES, Yaffe K Associations of Lower Extremity Peripheral Nerve Impairment and Risk of Dementia in Black and White Older Adults. Neurology 2022. March 9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35264428 https://n.neurology.org/content/early/2022/03/09/WNL.0000000000200185 - ↑ 100.0 100.1 Full KM, Pusalavidyasagar S, Palta P et al Associations of late-life sleep medication use with incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study. J Gerontol A Biol Sci Med Sci. 2022, April 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35421897 https://academic.oup.com/biomedgerontology/advance-article-abstract/doi/10.1093/gerona/glac088/6568591
- ↑ 101.0 101.1 101.2 Ehrlich JR, Goldstein J, Swenor BK et al Addition of Vision Impairment to a Life-Course Model of Potentially Modifiable Dementia Risk Factors in the US. JAMA Neurol. Published online April 25, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35467745 https://jamanetwork.com/journals/jamaneurology/fullarticle/2791268
Deal J, Rohas JC Visual Impairment as a Modifiable Risk Factor in Dementia Prevention and Management. JAMA Neurol. Published online April 25, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35467705 https://jamanetwork.com/journals/jamaneurology/fullarticle/2791267 - ↑ 102.0 102.1 102.2 102.3 George J Large Share of Alzheimer's, Dementia Cases Tied to 8 Modifiable Risk Factors. Midlife, early-life risk factors now more common, differ by sex, race/ethnicity. MedPage Today May 9, 2022 https://www.medpagetoday.com/neurology/dementia/98615
Nianogo RA, Rosenwohl-Mack A, Yaffe K et al Risk Factors Associated With Alzheimer Disease and Related Dementias by Sex and Race and Ethnicity in the US. JAMA Neurol. Published online May 9, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35532912 https://jamanetwork.com/journals/jamaneurology/article-abstract/2792227 - ↑ 103.0 103.1 Hashmi A New PPI Data Again Link Medication Use to Alzheimer's. Medscape. April 01, 2022 https://www.medscape.com/viewarticle/971414
Kwon MJ, Kim JH, Kim JH et al Associations between proton pump inhibitors and Alzheimer's disease: A nested case-control study using a Korean nationwide health screening cohort. Research Square. March 11, 2022 https://www.researchsquare.com/article/rs-1435267/v1 - ↑ 104.0 104.1 Crane PK et al. Association of traumatic brain injury with late-life neurodegenerative conditions and neuropathologic findings. JAMA Neurol 2016 Jul 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27400367 PMCID: PMC5319642 Free PMC article
Raj R, Kaprio J, Jousilahti P et al Risk of Dementia After Hospitalization Due to Traumatic Brain Injury: A Longitudinal, Population-Based Study. Neurology. 2022. May 11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35545443 https://n.neurology.org/content/early/2022/05/11/WNL.0000000000200290 - ↑ 105.0 105.1 Wang HX, Karp A, Herlitz A, Personality and lifestyle in relation to dementia incidence. Neurology. 2009 Jan 20;72(3):253-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19153372
George J Social Isolation Tied to Higher Risk of Subsequent Dementia. Isolation linked with lower brain volume in areas related to cognition. MedPage Today June 9, 2022 https://www.medpagetoday.com/neurology/dementia/99159
Shen C, Rolls E, Chen W et al Associations of Social Isolation and Loneliness With Later Dementia. Neurology. June 8, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35676089 https://n.neurology.org/content/early/2022/06/08/WNL.0000000000200583 - ↑ 106.0 106.1 Hamza Z NAFLD Tied to Higher Dementia Risk
Findings were stronger among patients with comorbid heart disease. MedPage Today July 13, 2022 https://www.medpagetoday.com/neurology/dementia/99704https://www.medpagetoday.com/neurology/dementia/99704
Shang Y, Widman L, Hagstrom H Nonalcoholic Fatty Liver Disease and Risk of Dementia: A Population-Based Cohort Study. Neurology. 2022. July 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35831178 https://n.neurology.org/content/early/2022/07/13/WNL.0000000000200853 - ↑ 107.0 107.1 Wieland DR, Wieland JR, Wang H et al Thyroid Disorders and Dementia Risk: A Nationwide Population-Based Case-Control Study Neurology. 2022 Jul 6:10.1212/WNL.0000000000200740. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35794019 https://n.neurology.org/content/early/2022/07/06/WNL.0000000000200740
- ↑ 108.0 108.1 108.2 George J ICU Stay Doubles Dementia Risk. Higher risks of both Alzheimer's and all-type dementia seen. MedPage Today August 2, 2022. https://www.medpagetoday.com/meetingcoverage/aaic/100018
- ↑ Norton MC, Smith KR, Ostbye T et al Greater risk of dementia when spouse has dementia? The Cache County study. J Am Geriatr Soc. 2010 May;58(5):895-900 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20722820 PMCID: PMC2945313 DOI: Free PMC article
- ↑ 110.0 110.1 Cairns DM, Itzhaki RF, Kaplan DL Potential Involvement of Varicella Zoster Virus in Alzheimer's Disease via Reactivation of Quiescent Herpes Simplex Virus Type 1. J Alzheimers Dis. 2022;88(3):1189-1200 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35754275 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad220287
- ↑ 111.0 111.1 111.2 Calvin CM, Conroy MC, Moore SF et al Association of Multimorbidity, Disease Clusters, and Modification by Genetic Factors With Risk of Dementia. JAMA Netw Open. 2022;5(9):e2232124 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36125811 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2796543
- ↑ 112.0 112.1 Li H et al. Association of ultraprocessed food consumption with risk of dementia: A prospective cohort study. Neurology 2022 Jul 27; 99:e1056. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35896436 https://n.neurology.org/content/99/10/e1056
- ↑ 113.0 113.1 Brooks M Not Just a Bad Dream: Nightmares May Predict Dementia. Medscape. Sept 26, 2022 https://www.medscape.com/viewarticle/981468
- ↑ 114.0 114.1 Romero JR et al. MRI visible perivascular spaces and risk of incident dementia: The Framingham Heart Study. Neurology 2022 Sep 29; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36175148 https://n.neurology.org/content/early/2022/09/29/WNL.0000000000201293
- ↑ 115.0 115.1 Li J, Liu C, Ang TFA, Au R BMI decline patterns and relation to dementia risk across four decades of follow-up in the Framingham Study. Alzheimer's & Dementia 2022. Dec 15. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36519667 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12839
- ↑ 116.0 116.1 George J Dementia Risk Higher in People With Earlier Signs of Psychological Distress. Stress, exhaustion symptoms linked with increased dementia risk years later. MedPage Today December 16, 2022
- ↑ 117.0 117.1 George J Earlier Health Conditions Tied to Subsequent Dementia. Alzheimer's disease, vascular dementia links are time-dependent. MedPage Today January 5, 2023 https://www.medpagetoday.com/neurology/dementia/102521
Beason-Held LL, Kerley CI, Chaganti S et al Health Conditions Associated with Alzheimer's Disease and Vascular Dementia. Ann Neurol. 2022. Dec 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36571386 https://onlinelibrary.wiley.com/doi/10.1002/ana.26584 - ↑ 118.0 118.1 George J Dementia Risk Higher After Hospital Stay With Infection. Is neuroinflammation a factor? MedPage Today January 9, 2023 https://www.medpagetoday.com/neurology/dementia/102551
Bohn B, Lutsey PL, Misialek JR et al Incidence of Dementia Following Hospitalization With Infection Among Adults in the Atherosclerosis Risk in Communities (ARIC) Study Cohort. JAMA Netw Open. 2023;6(1):e2250126 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36622673 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800141 - ↑ 119.0 119.1 119.2 Huang AR, Roth DL, Cidav T et al Social isolation and 9-year dementia risk in community-dwelling Medicare beneficiaries in the United States. J Am Geriatr Soc. 2023. Jan 11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36628523 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18140
- ↑ 120.0 120.1 Short E Cutting Back on Smoking No Help for Dementia Risk. But large study of long-time smokers confirms reduced risk with quitting altogether. MedPage Today January 19, 2023 https://www.medpagetoday.com/pulmonology/smoking/102701
Jeong SM, Park J, Han K et al Association of Changes in Smoking Intensity With Risk of Dementia in Korea. JAMA Netw Open. 2023;6(1):e2251506 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36656579 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800609 - ↑ 121.0 121.1 George J Dementia Risk Tied to Blood Pressure Fluctuations. Relationship was stronger in people not taking calcium channel blockers. MedPage Today January 20, 2023 https://www.medpagetoday.com/neurology/dementia/102733
Mahinrad S et al Blood pressure variability, dementia, and role of antihypertensive medications in older adults. Alzheimer's & Dementia 2023. Jan 19 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36656086 https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.12935 - ↑ 122.0 122.1 George J Viruses Tied to Subsequent Dementia, Other Neurodegenerative Diseases. Viral encephalitis and Alzheimer's disease showed strongest links. MedPage Today January 30, 2023 https://www.medpagetoday.com/neurology/generalneurology/102872
Levine KS, Leonard HL, Blauwendraat C et al Virus exposure and neurodegenerative disease risk across national biobanks. Neuron. 2023. Jan 19 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36669485Free article https://www.cell.com/neuron/fulltext/S0896-6273(22)01147-3 - ↑ 123.0 123.1 Douros A et al. Common vaccines and the risk of incident dementia: A population-based cohort study. J Infect Dis 2022 Dec 21; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36542511 https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiac484/6948438
Salmon DA et al. Commentary on "Common vaccines and the risk of dementia: a population-based cohort study": Science can be messy but eventually leads to truths. J Infect Dis 2022 Dec 21; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/36542509 https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac487/6950650 - ↑ 124.0 124.1 Pourhadi N, Morch LS, Holm EA, Torp-Pedersen C, Meaidi A. Menopausal hormone therapy and dementia: nationwide, nested case-control study. BMJ 2023;381:e072770 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37380194 PMCID: PMC10302215 Free PMC article https://www.bmj.com/content/381/bmj-2022-072770
- ↑ 125.0 125.1 Daghlas I, Nassan M, Gill D. Genetically proxied lean mass and risk of Alzheimer's disease: mendelian randomisation study. https://bmjmedicine.bmj.com/content/2/1/e000354
- ↑ 126.0 126.1 Powell WR, Vilen L, Zuelsdorff M et al Association between military service and Alzheimer's disease neuropathology at autopsy. Alzheimer's & Dementia. 2023. Nov 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37965965 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13520
- ↑ 127.0 127.1 George J Coronary Heart Disease by Age 45 Linked With Subsequent Dementia. All-cause dementia, Alzheimer's disease, and vascular dementia risks elevated. MedPage Today November 29, 2023 https://www.medpagetoday.com/neurology/dementia/107594
Lang J, Li C, Gao D et al Association Between Onset Age of Coronary Heart Disease and Incident Dementia: A Prospective Cohort Study. J Am Heart Assoc. 2023;0:e031407 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38018492 https://www.ahajournals.org/doi/full/10.1161/JAHA.123.031407 - ↑ 128.0 128.1 Banerjee G, Farmer SF, Hyare H Iatrogenic Alzheimer's disease in recipients of cadaveric pituitary-derived growth hormone. Nat Med. 2024 Jan 29. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38287166 https://www.nature.com/articles/s41591-023-02729-2
- ↑ 129.0 129.1 Cammann D, Lu Y, Cummings MJ et al Genetic correlations between Alzheimer's disease and gut microbiome genera. Sci Rep. 2023 Mar 31;13(1):5258. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37002253 PMCID: PMC10066300 Free PMC article. https://www.nature.com/articles/s41598-023-31730-5
- ↑ 130.0 130.1 George J Alzheimer's Risk Higher If Mom Had Memory Problems. Maternal history of memory impairment tied to higher amyloid burden. MedPage Today June 17, 2024 https://www.medpagetoday.com/neurology/alzheimersdisease/110682
Seto M, Hohman TJ, Mormino EC et al Parental History of Memory Impairment and beta-Amyloid in Cognitively Unimpaired Older Adults. JAMA Neurol. Published online June 17, 2024 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38884955 https://jamanetwork.com/journals/jamaneurology/fullarticle/2820195 - ↑ 131.0 131.1 Lennon MJ, Lipnicki DM, Lam BCP et al Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk: An Individual Participant Data Meta-Analysis. Neurology. 2024 Sep 10;103(5):e209715. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39141884 https://www.neurology.org/doi/10.1212/WNL.0000000000209715
- ↑ 132.0 132.1 George J Emerging Depression Tied to Earliest Alzheimer's Pathology. Symptoms linked with very early amyloid accumulation in emotional control brain regions. MedPage Today August 29, 2024 https://www.medpagetoday.com/neurology/alzheimersdisease/111731
Munro CE, Farrell M, Hanseeuw B et al Change in Depressive Symptoms and Longitudinal Regional Amyloid Accumulation in Unimpaired Older Adults. JAMA Netw Open. 2024;7(8):e2427248 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822957 - ↑ 133.0 133.1 Wendling P Nighttime Outdoor Light Pollution Linked to Alzheimer's Risk. Medscape. Sept 6, 2024 https://www.medscape.com/viewarticle/nighttime-outdoor-light-pollution-linked-alzheimers-risk-2024a1000g60 - Voigt RM, Ouyang B, Keshavarzian A et al Outdoor nighttime light exposure (light pollution) is associated with Alzheimer's disease. medRxiv [Preprint]. 2024 Feb 15:2024.02.14.24302831 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38405987 PMCID: PMC10889016 Free PMC article. Front. Neurosci., 05 September 2024 https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1378498/full
- ↑ 134.0 134.1 Brier MR, Schindler SE, Salter A et al Unexpected Low Rate of Amyloid-beta Pathology in Multiple Sclerosis Patients. Ann Neurol. 2024 Sep;96(3):453-459 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38963256 PMCID: PMC11324391 (available on 2025-09-01)
- ↑ 135.0 135.1 Park G, Kadyan S, Hochuli N et al An Enteric Bacterial Infection Triggers Neuroinflammation and Neurobehavioral Impairment in 3xTg-AD Transgenic Mice. J Infect Dis. 2024 Sep 10;230(Supplement_2):S95-S108. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39255397
- ↑ 136.0 136.1 136.2 Alzheimer's Association 2024. Alzheimer's disease facts and figures Special report: mapping of better future for dementia care navigation Alzheimers Dement 2024;20(5) https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf