Restricted accessResearch articleFirst published online 2016-3
A methodological critique of the National Institute of Aging and Alzheimer’s Association Guidelines for Alzheimer’s disease,dementia,and mild cognitive impairments
In 2011, the U.S. National Institute on Aging published guidelines for clinical diagnostics for Alzheimer’s disease dementia. These guidelines define a continuum with three stages—an early, pre-clinical stage with no symptoms, followed by mild cognitive impairment, and a final stage of Alzheimer’s disease dementia. This methodological critique examines the validity of this continuum. No studies exist showing the progression of these biomarkers to Alzheimer’s disease. There is also a lack of empirical evidence showing how biomarkers determine mild cognitive impairment, which has multiple etiologies. The guidelines fail to explain anomalies where there are biomarkers but no expression of Alzheimer’s disease.
AlbertM. S.DeKoskyS. T.DicksonD.DuboisB.FeldmanH. H.FoxN. C.PhelpsC. H. (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia7(3): 270–279.
ArteroS.AncelinM. L.PortetF.DupuyA.BerrC.DartiguesJ. F.RitchieK. (2008) Risk profiles for mild cognitive impairment and progression to dementia are gender specific. Journal of Neurology, Neurosurgery & Psychiatry79(9): 979–984.
4.
BalasubramanianA. B.KawasC. H.PeltzC. B.BrookmeyerR.CorradaM. M. (2012) Alzheimer disease pathology and longitudinal cognitive performance in the oldest-old with no dementia. Neurology79(9): 915–921.
5.
BallK.BerchD. B.HelmersK. F.JobeJ. B.LeveckM. D.MarsiskeM.WillisS. L. (2002) Effects of cognitive training interventions with older adults: A randomized controlled trial. Journal of the American Medical Association288(18): 2271–2281.
6.
BelandF.ZunzuneguiM.AlvaradoB.OteroA.del SerT. (2006) Trajectories of cognitive decline and social relations. Journals of Gerontology: Psychological Sciences60B(6): 320–330.
7.
Brainerd, C. J., Reyna, V. F., Gomes, C. F. A., Kenney, A. E., Gross, C. J., Taub, E. S., … Spreng, R. N. (2013). Dual-retrieval models and neurocognitive impairment. Journal of Experimental Psychology: Learning, Memory, and Cognition. Advance online publication. doi: 10.1037/a0034057. Retrieved from http://www.apa.org/pubs/journals/features/xlm-a0034057.pdf.
8.
Brumback-PeltzC.BalasubramanianA. B.CorradaM. M.KawasC. H. (2011) Diagnosing dementia in the oldest-old. Maturitas70(2): 164–168.
9.
BusseA.BischkopfJ.Riedel-HellerS. G.AngermeyerM. C. (2003) Mild cognitive impairment: Prevalence and predictive validity according to current approaches. Acta Neurologica Scandinavica108(2): 71–81.
10.
ChristakisN. A. (1999) Death Foretold: Prophecy and Prognosis in Medical Care, Chicago: University of Chicago Press.
11.
ClarkC. M.DeCarlsC.MungasD.ChuiH.HigdonR.NuñezJ.van BelleG. (2005) Earlier onset of Alzheimer’s disease symptoms in Latino individuals compared with White individuals. Archives of Neurology62: 774–778.
12.
Correa-LeiteM.NicolosiA.CristinaS.HauserW.NappiG. (2001) Nutrition and cognitive deficit in the elderly: A population study. European Journal of Clinical Nutrition55: 1053–1058.
13.
CrystalH.DicksonD.FuldP.MasurD.ScottR.MehlerM.WolfsonL. (1988) Clinico-pathologic studies in dementia Nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology38(11): 1682–1682.
14.
CrystalH. A.DicksonD.DaviesP.MasurD.GroberE.LiptonR. B. (2000) The relative frequency of “dementia of unknown etiology” increases with age and is nearly 50% in nonagenarians. Archives of Neurology57(5): 713–719.
15.
Dams-O'ConnorK.GibbonsL. E.BowenJ. D.McCurryS. M.LarsonE. B.CraneP. K. (2013) Risk for late-life re-injury, dementia and death among individuals with traumatic brain injury: a population-based study. Journal of Neurology, Neurosurgery & Psychiatry84(2): 177–182.
16.
DanielR. W.RowsonS.DumaS. M. (2012) Head impact exposure in youth football. Annals of Biomedical Engineering40(4): 976–987.
17.
DavisD. G.SchmittF. A.WeksteinD. R.MarkesberyW. R. (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. Journal of Neuropathology and Experimental Neurology58: 376–388.
18.
DeCarliC. (2003) Mild cognitive impairment: Prevalence, prognosis, aetiology, and treatment. The Lancet Neurology2(1): 15–21.
19.
den DunnenW. F.BrouwerW. H.BijlardE.KamphuisJ.van LinschotenK.Eggens-MeijerE.HolstegeG. (2008) No disease in the brain of a 115-year-old woman. Neurobiology of Aging29(8): 1127–1132.
20.
DuboisB.FeldmanH. H.JacovaC.CummingsJ. L.DeKoskyS. T.Barberger-GateauP.ScheltensP. (2010) Revising the definition of Alzheimer's disease: A new lexicon. The Lancet Neurology9(11): 1118–1127.
21.
DziewczapolskiG.GlogowskiC. M.MasliahE.HeinemannS. F. (2009) Deletion of the α7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease. The Journal of Neuroscience29(27): 8805–8815.
22.
EsiriM. M. (2010) Can neuropathology really confirm the exact diagnosis?Alzheimer's Research & Therapy2: 10.
23.
EspinosaA.AlegretM.ValeroS.Vinyes-JunquéG.HernándezI.MauleónA.BoadaM. A. (2013) Longitudinal follow-up of 550 mild cognitive impairment patients: Evidence for large conversion to dementia rates and detection of major risk factors involved. Journal of Alzheimer's Disease34(3): 769–780.
24.
EvertJ.LawlerE.BoganH.PerlsT. (2003) Morbidity profiles of centenarians: Survivors, delayers, and escapers. Journals of Gerontology Series A: Biological Sciences and Medical Sciences58(3): 232–237.
25.
Faul, M., Xu, L., Wald, M. M., & Coronado, V. G. (2010). Traumatic brain injury in the united states: emergency department visits, hospitalizations and deaths 2002–2006. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2010. Retrieved from http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf.
26.
FischerP.JungwirthS.ZehetmayerS.WeissgramS.HoenigschnablS.GelpiE.TraglK. H. (2007) Conversion from subtypes of mild cognitive impairment to Alzheimer dementia. Neurology68(4): 288–291.
27.
FlickerC.StevenH.FerrisS. H.Barry ReisbergB. (1991) Mild cognitive impairment in the elderly: Predictors of dementia. Neurology41(7): 1006.
28.
FratiglioniL.De RonchiD.Agüero-TorresH. (1999) Worldwide prevalence and incidence of dementia. Drugs & Aging15(5): 365–375.
29.
FrisoniG. B.FratiglioniL.FastbomJ.GuoZ.ViitanenM.WinbladB. (2000) Mild cognitive impairment in the population and physical health data on 1,435 individuals aged 75 to 95. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences55(6): M322–M328.
30.
FullerG. N. (2011) Neurologists and the “doctors with desks” fallacy. Practical Neurology11(5): 270–271.
31.
GageF. H. (2003) Brain, repair yourself. Scientific American289(3): 46–53.
32.
GanguliM.DodgeH. H.ShenC.DeKoskyS. T. (2004) Mild cognitive impairment, amnestic type: An epidemiologic study. Neurology63(1): 115–121.
33.
GauthierS.ReisbergB.ZaudigM.PetersenR. C.RitchieK.BroichK.International Psychogeriatric Association Expert Conference on mild cognitive impairment (2006) Mild cognitive impairment. Lancet367: 1262–1270.
34.
GuerrieroR. M.ProctorM. R.MannixR.MeehanW. P. (2012) Epidemiology, trends, assessment and management of sport-related concussion in United States high schools. Current Opinion in Pediatrics24(6): 696–701.
35.
HaanM. N.MungasD. M.GonzalezH. M.OrtizT. A.AcharyaA.JagustW. J. (2003) Prevalence of dementia in older Latinos: The influence of type 2 diabetes mellitus, stroke and genetic factors. Journal of the American Geriatrics Society51(2): 169–177.
36.
HarrisonT. M.WeintraubS.MesulamM. M.RogalskiE. (2012) Superior memory and higher cortical volumes in unusually successful cognitive aging. Journal of the International Neuropsychological Society18(6): 1081.
37.
HoltzmanR. E.RebokG. W.SaczynskiJ. S.KouzisA. C.DoyleK. W.EatonW. W. (2004) Social network characteristics and cognition in middle-aged and older adults. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences59(6): P278–P284.
38.
HymanB. T.PhelpsC. H.BeachT. G.BigioE. H.CairnsN. J.CarrilloM. C.MontineT. J. (2012) National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimer's & Dementia8(1): 1–13.
39.
ImhofA.KövariE.von GuntenA.GoldG.RivaraC. B.HerrmannF. R.GiannakopoulosP. (2007) Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?Journal of the Neurological Sciences257(1): 72–79.
40.
JackC. R.JrAlbertM. S.KnopmanD. S.McKhannG. M.SperlingR. A.CarrilloM. C.PhelpsC. H. (2011) Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia7(3): 257–262.
41.
JackC. R.JrKnopmanD. S.JagustW. J.ShawL. M.AisenP. S.WeinerM. W.TrojanowskiJ. Q. (2010) Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurology9: 119–128.
42.
JellingerK. A. (2008) Morphologic diagnosis of “vascular dementia” – A critical update. Journal of Neurological Sciences270: 1–12.
43.
JohnsonV. E.StewardW.SmithD. H. (2012) Widespread and amyloid-pathology many years after a single traumatic brain injury in humans. Brain Pathology22(2): 142–149.
44.
KatzmanR.TerryR. D.DeTeresaR.BrownT.DaviesP.FuldP.PeckA. (1988) Clinical, pathological, and neurochemical changes in dementia: A subgroup with preserved mental status and numerous neocortical plaques. Annals of Neurology23(2): 138–144.
45.
KerrZ. Y.MarshallS. W.GuskiewiczK. M. (2012) Reliability of concussion history in former professional players. Medicine and Science in Sports and Exercise44(3): 377–382.
46.
KirshnerH. S. (2008) Approaches to intellectual and memory impairments. In: GradleyW. G.DaroffR. B.FenichelG. M.JankovicJ. (eds) Neurology in clinical practice. (Chapter 6, 5th ed.). Philadelphia, PA: Butterworth-Heinemann.
47.
KnopmanD. S.ParisiJ. E.SalviatiA.Floriach-RobertM.BoeveB. F.IvnikR. J.PetersenR. C. (2003) Neuropathology of cognitively normal elderly. Journal of Neuropathology and Experimental Neurology62: 1087–1095.
48.
KoerteI. K.Ertl-WagnerB.ResierM.ZafonteR.ShentonM. E. (2012) White matter integrity in the brains of professional soccer players without a symptomatic concussion. The Journal of the American Medical Association308(18): 1859–1861.
49.
KubzanskyL. D.BerkmanL. F.GlassT. A.SeemanT. E. (1998) Is educational attainment associated with shared determinants of health in the elderly? Findings from the MacArthur studies of successful aging. Psychosomatic Medicine60(5): 578–585.
50.
LarrieuS.LetenneurL.OrgogozoJ. M.FabrigouleC.AmievaH.Le CarretN.DartiguesJ. F. (2002) Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology59: 1594–1599.
51.
LowL.HarrisonF.KochanN. A.DraperB.SlavinM. J.ReppermundS.BrodatyH. (2012) Can mild cognitive impairment be accurately diagnosed in English speakers from linguistic minorities? Results from the Sydney memory and ageing study. The American Journal of Geriatric Psychiatry20(10): 866–877.
52.
MahnckeH. W.BronstoneA.MerzenichM. M. (2006) Brain plasticity and functional losses in the aged: Scientific bases for a novel intervention. Progress in brain research157: 81–109.
53.
ManlyJ. J.Bell-McGintyS.TangM. X.SchupfN.SternY.MayeuxR. (2005) Implementing diagnostic criteria and estimating frequency of mild cognitive impairment in an urban community. Archives of Neurology62(11): 1739–1746.
54.
MattssonN.BraxD.ZetterbergH. (2010) To know or not to know: Ethical issues related to early diagnosis of Alzheimer's disease. International Journal of Alzheimer's Disease2010: . doi: 10.4061/2010/841941. Retrieved from http://www.hindawi.com/journals/ijad/2010/841941/.
55.
MayeuxR. (2004) Biomarkers: Potential uses and limitations. NeuroRx1(2): 182–188.
56.
McDougallG. J. (2000) Memory improvement in assisted living elders. Issues in mental health nursing21(2): 217–233.
57.
McKhannG. M.KnopmanD. S.ChertkowH.HymanB. T.JackC. R.JrKawasC. H.PhelpsC. H. (2011) The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia7(3): 263–269.
58.
McShane, R., Noel Storr, A., Ritchie, C. W., & Flicker, L. (2011). The quality and extent of evidence for biomarkers: A Cochrane systematic review. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 7(4), Supplement, Pages S100–S101. doi:10.1016/j.jalz.2011.05.248.
59.
MesulamM. M. (1987) Primary progressive aphasia-differentiation from AD [editorial]. Annals of Neurology22: 533–534.
MirelesD.CharnessN. (2002) Computational explorations of the influence of structured knowledge on age-related cognitive decline. Psychology & Aging17: 245–259.
62.
MorettiL.CristoforiI.WeaverS. M.ChauA.PortelliJ. N.GrafmanJ. (2012) Cognitive decline in older adults with a history of traumatic brain injury. The Lancet Neurology11(12): 1103–1112.
OjofeitimiE. O.IjadunolaK. T.JegedeV. A.FreemanY. A.OwolabiO. O.FreemanA. S.FabiyiA. K. (2002) Nutritional status and physical activity in relation to cognitive function in a group of elderly in Nigeria. Journal of Nutrition for the Elderly22(1): 49–62.
65.
OrnishD.LinJ.DaubenmierJ.WeidnerG.EpelE.KempC.BlackburnE. H. (2008) Increased telomerase activity and comprehensive lifestyle changes: A pilot study. The Lancet Oncology9(11): 1048–1057.
66.
PetersenR. C.SmithG. E.WaringS. C.IvnikR. J.TangalosE.G.KokmenE. (1999) Mild cognitive impairment: Clinical characterization and outcome. Archives of Neurology56: 303–308.
67.
PetersenR. C.DoodyR.KurzA.MohsR. C.MorrisJ. C.RabinsP. V.WinbladB. (2001) Current concepts in mild cognitive impairment. Archives of Neurology58(12): 1985–1992.
68.
PolvikoskiT.SulkavaR.MyllykangasL.NotkolaI. L.NiinistoL.VerkkoniemiA.HaltiaM. (2001) Prevalence of Alzheimer's disease in very elderly people: A prospective neuropathological study. Neurology56(12): 1690–1696.
69.
PopperK. (2004) Conjectures and refutations: The growth of scientific knowledge, London: Routledge.
70.
PriceJ. L.MorrisJ. C. (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease. Annals of Neurology45: 358–368.
71.
RitchieK.ArteroS.TouchonJ. (2001) Classification criteria for mild cognitive impairment: A population-based validation study. Neurology56(1): 37–42.
72.
RoenkerD. L.CissellG. M.BallK. K.WadleyV. G.EdwardsJ. D. (2003) Speed-of-processing and driving simulator training result in improved driving performance. Human Factors: The Journal of the Human Factors and Ergonomics Society45(2): 218–233.
73.
RomeroJ. R.MercadoM.BeiserA. S.PikulaA.SeshadriS.Kelly-HayesM.KaseC. S. (2013) Transient global amnesia and neurological events: The Framingham Heart Study. Frontiers in Neurology4: Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653124/\.
74.
SalthouseT. A. (2006) Mental exercise and mental aging: Evaluating the validity of the “use it or lose it” hypothesis. Perspectives on Psychological Science1(1): 68–87.
75.
SavvaG. M.WhartonS. B.InceP. G.ForsterG.MatthewsF. E.BrayneC. (2009) Age, neuropathology, and dementia. New England Journal of Medicine360(22): 2302–2309.
76.
SchaieK.WillisS.CaskieG. (2004) The Seattle longitudinal study: Relationship between personality and cognition. Neuropsychology of Cognition11: 304–324.
77.
SchillerJ. S.LucasJ. W.PeregoyJ. A. (2012) Summary health statistics for U.S. adults: National Health Interview Survey, 2011. National Center for Health Statistics. Vital and Health Statistics10(256): Retrieved from http://www.cdc.gov/nchs/data/series/sr_10/sr10_256.pdf.
78.
ShupingJ. R.RollinsonR. D.TooleJ. F. (1980) Transient global amnesia. Annals of Neurology7(3): 281–285.
79.
SnowdonD. (1997) Aging and Alzheimer's disease: Lessons from the Nun study. The Gerontologist37(2): 150–156.
80.
SnowdonD. A. (2003) Healthy aging and dementia: findings from the Nun Study. Annals of Internal Medicine139(5_Part_2): 450–454.
81.
SnowdonD.KemperS.MortimerJ.GreinerL.WeksteinD.MardesberyW. (1996) Linguistic ability in early life and cognitive function and Alzheimer's disease in late life: Findings from the Nun study. Journal of the American Medical Association275(7): 528–533.
82.
SperlingR. A.AisenP. S.BeckettL. A.BennettD. A.CraftS.FaganA. M. (2011) Towards defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement7: 280–292.
83.
StephanB. C. M.MinettT.PagettE.SiervoM.BrayneC.McKeithI. G. (2013) Diagnosing mild cognitive impairment (MCI) in clinical trials: A systematic review. BMJ Open3(2): Retrieved from http://bmjopen.bmj.com/content/3/2/e001909.full.
TangM. X.SternY.MarderK.BellK.GurlandB.LantiguaR.MayeuxR. (1998) The APOE-ε4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA: The Journal of the American Medical Association279(10): 751–755.
86.
TengE.TingusK. D.LuP. H.CummingsJ. L. (2009) Persistence of neuropsychological testing deficits in mild cognitive impairment. Dementia and Geriatric Cognitive Disorders28(2): 168–178.
87.
TheriaultM.De BeaumontL.TremblayS.LassondeM.JolicoeurP. (2011) Cumulative effects of concussions in athletes revealed by electrophysiological abnormalities on visual working memory. Journal of Clinical and Experimental Neuropsychology33(1): 30–41.
88.
ValleR.GarrettM. D.VelasquezR. (2013) Developing dementia prevalence rates among latinos: a locally-attuned, data-based, service planning tool. Journal of Population Ageing6(3): 211–225.
89.
van GelderB.TijhuisM.KalmijnS.GiampaoliS.NissinenA.KromhoutD. (2004) Physical activity in relation to cognitive decline in elderly men: The FINE study. Neurology63: 2316–2321.
90.
WangH. K.LinS. H.SungP. S.WuM. H.HungK. W.WangL. C.TsaiK. J. (2012) Population based study on patients with traumatic brain injury suggests increased risk of dementia. Journal of Neurology, Neurosurgery & Psychiatry83(11): 1080–1085.
91.
WeuveJ.KangJ.MansonJ. E.BretelerM. M. B.WareJ. G.GrodsteinF. (2004) Physical activity, including walking, and cognitive function in older women. Journal of the American Medical Association292(12): 1454–1461.
92.
WhitehairD. C.SherzaiA.EmondJ.RamanR.AisenP. S.PetersenR. C.FleisherA. S. (2010) Influence of apolipoprotein e (epsilon)4 on rates of cognitive and functional decline in mild cognitive impairment. Alzheimer's Dementia6: 412–419.
93.
WilkJ. E.HerrellR. K.WynnG. H.RiviereL. A.HogeC. W. (2012) Mild traumatic brain injury (concussion), posttraumatic stress disorder, and depression in US soldiers involved in combat deployments: association with association with postdeployment symptoms. Psychosomatic Medicine74(3): 249–257.
94.
WilliamsK.KemperS. (2011) Exploring interventions to reduce cognitive decline in aging. Journal of Psychosocial Nursing and Mental Health Services48(5): 42–51.
95.
WillisS. L.TennstedtS. L.MarsiskeM.BallK.EliasJ.KoepkeK. M.ACTIVE Study Group (2006) Long-term effects of cognitive training on everyday functional outcomes in older adults. Jama296(23): 2805–2814.
96.
WolinskyF. D.UnverzagtF. W.SmithD. M.JonesR.StoddardA.TennstedtS. L. (2006) The ACTIVE cognitive training trial and health-related quality of life: Protection that lasts for 5 years. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences61(12): 1324–1329.
97.
YaffeK.BarnesD.NevittM.LuiL.CovinskyK. (2001) A prospective study of physical activity and cognitive decline in elderly women: Women who walk. Archives of Internal Medicine161: 1703–1708.
