Effects of Meditation and Music-Listening on Blood Biomarkers of Cellular Aging and Alzheimer’s Disease in Adults with Subjective Cognitive Decline: An Exploratory Randomized Clinical Trial
Restricted accessResearch articleFirst published online November 23, 2018
Effects of Meditation and Music-Listening on Blood Biomarkers of Cellular Aging and Alzheimer’s Disease in Adults with Subjective Cognitive Decline: An Exploratory Randomized Clinical Trial
Telomere length (TL), telomerase activity (TA), and plasma amyloid-β (Aβ) levels have emerged as possible predictors of cognitive decline and dementia.
Objective:
To assess the: 1) effects of two 12-week relaxation programs on TL, TA, and Aβ levels in adults with subjective cognitive decline; and 2) relationship of biomarker changes to those in cognitive function, psychosocial status, and quality of life (QOL).
Methods:
Participants were randomized to a 12-week Kirtan Kriya meditation (KK) or music listening (ML) program and asked to practice 12 minutes/day. Plasma Aβ(38/40/42) and peripheral blood mononuclear cell TL and TA were measured at baseline and 3 months. Cognition, stress, sleep, mood, and QOL were assessed at baseline, 3 months, and 6 months.
Results:
Baseline blood samples were available for 53 participants (25 KK, 28 ML). The KK group showed significantly greater increases in Aβ40 than the ML group. TA rose in both groups, although increases were significant only among those with higher practice adherence and lower baseline TA. Changes in both TL and TA varied by their baseline values, with greater increases among participants with values ≤50th percentile (ps-interaction <0.006). Both groups improved in cognitive and psychosocial status (ps ≤0.05), with improvements in stress, mood, and QOL greater in the KK group. Rising Aβ levels were correlated with gains in cognitive function, mood, sleep, and QOL at both 3 and 6 months, associations that were particularly pronounced in the KK group. Increases in TL and TA were also correlated with improvements in certain cognitive and psychosocial measures.
Conclusion:
Practice of simple mind-body therapies may alter plasma Aβ levels, TL, and TA. Biomarker increases were associated with improvements in cognitive function, sleep, mood, and QOL, suggesting potential functional relationships.
de LangeT (2009) How telomeres solve the end-protection problem. Science326, 948–952.
2.
LudlowAT, LudlowLW, RothSM (2013) Do telom-eres adapt to physiological stress? Exploring the effect of exercise on telomere length and telomere-related proteins. Biomed Res Int2013, 601368.
3.
P TzanetakouI, NzietchuengR, N PerreaD, BenetosA (2014) Telomeres and their role in aging and longevity. Curr Vasc Pharmacol12, 726–734.
4.
EpelES, BlackburnEH, LinJ, DhabharFS, AdlerNE, MorrowJD, CawthonRM (2004) Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U SA101, 17312–17315.
5.
HinterbergerM, FischerP, HuberK, KruglugerW, Zehet-mayerS (2017) Leukocyte telomere length is linked to vascular risk factors not to Alzheimer’s disease in the VITA study. J Neural Transm124, 1–11.
6.
LinJ, EpelE, BlackburnE (2012) Telomeres and lifestyle factors: Roles in cellular aging. Mutat Res730, 85–89.
7.
ShalevI, EntringerS, WadhwaPD, WolkowitzOM, Put-ermanE, LinJ, EpelES (2013) Stress and telomere biology: A lifespan perspective. Psychoneuroendocrinology38, 1835–1842.
8.
RobertsRO, BoardmanLA, ChaRH, PankratzVS, JohnsonRA, DrulinerBR, ChristiansonTJH, RobertsLR, PetersenRC (2014) Short and long telomeres increase risk of amnestic mild cognitive impairment. Mech Ageing Dev141-142, 64–69.
9.
DevoreEE, PrescottJ, De VivoI, GrodsteinF (2011) Relative telomere length and cognitive decline in the Nurses’ Health Study. Neurosci Lett492, 15–18.
10.
HonigLS, KangMS, SchupfN, LeeJH, MayeuxR (2012) Association of shorter leukocyte telomere repeat length with dementia and mortality. Arch Neurol69, 1332–1339.
11.
HarrisSE, MarioniRE, Martin-RuizC, PattieA, GowAJ, CoxSR, CorleyJ, von ZglinickiT, StarrJM, DearyIJ (2016) Longitudinal telomere length shortening and cognitive and physical decline in later life: The Lothian Birth Cohorts 1936 and 1921. Mech Ageing Dev154, 43–48.
12.
YaffeK, LindquistK, KluseM, CawthonR, HarrisT, HsuehW-C, SimonsickEM, KullerL, LiR, AyonayonHN, RubinSM, CummingsSR, Health ABC Study (2011) Telomere length and cognitive function in community-dwelling elders: Findings from the Health ABC Study. Neurobiol Aging32, 2055–2060.
13.
WangJ, ZhaoC, ZhaoA, LiM, RenJ, QuX (2015) New insights in amyloid beta interactions with human telomerase. J Am Chem Soc137, 1213–1219.
14.
RembachA, FauxNG, WattAD, PertileKK, RumbleRL, TrounsonBO, FowlerCJ, RobertsBR, PerezKA, LiQX, LawsSM, TaddeiK, Rainey-SmithS, RobertsonJS, VandijckM, VandersticheleH, BarnhamKJ, EllisKA, SzoekeC, MacaulayL, RoweCC, VillemagneVL, AmesD, MartinsRN, BushAI, MastersCL, AIBL research group (2014) Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer’s disease. Alzheimers Dement10, 53–61.
15.
ChourakiV, BeiserA, YounkinL, PreisSR, WeinsteinG, HanssonO, SkoogI, LambertJ-C, AuR, LaunerL (2015) Plasma amyloid-β and risk of Alzheimer’s disease in the Framingham Heart Study. Alzheimers Dement11, 249-257. e241.
16.
KoyamaA, OkerekeOI, YangT, BlackerD, SelkoeDJ, GrodsteinF (2012) Plasma amyloid-beta as a predictor of dementia and cognitive decline: A systematic review and meta-analysis. Arch Neurol69, 824–831.
17.
BlaskoI, KemmlerG, JungwirthS, WichartI, KramplaW, WeissgramS, JellingerK, TraglKH, FischerP (2010) Plasma amyloid beta-42 independently predicts both late-onset depression and Alzheimer disease. Am J Geriatr Psychiatry18, 973–982.
18.
SongF, PoljakA, ValenzuelaM, MayeuxR, SmytheGA, SachdevPS (2011) Meta-analysis of plasma amyloid-beta levels in Alzheimer’s disease. J Alzheimers Dis26, 365–375.
19.
BenedictC, BybergL, CedernaesJ, HogenkampPS, GiedratisV, KilanderL, LindL, LannfeltL, SchiothHB (2015) Self-reported sleep disturbance is associated with Alzheimer’s disease risk in men. Alzheimers Dement11, 1090–1097.
20.
LovheimH, ElghF, JohanssonA, ZetterbergH, BlennowK, HallmansG, ErikssonS (2017) Plasma concentrations of free amyloid beta cannot predict the development of heimer’s disease. Alzheimers Dement13, 778–782.
21.
MettiAL, CauleyJA, AyonayonHN, HarrisTB, Rosano WilliamsonJD, YaffeK, Health, Aging and Body Composition Study (2013) The demographic and medical correlates of plasma A beta 40 and A beta 42. Alzheimer Dis Assoc Disord27, 244–249.
22.
PetersKE, DavisWA, TaddeiK, MartinsRN, MastersCL, DavisTME, BruceDG (2017) Plasma amyloid-beta peptides in type 2 diabetes: A matched case-control study. J Alzheimers Dis56, 1127–1133.
23.
LiX, SongD, LengSX (2015) Link between type 2 diabetes and Alzheimer’s disease: From epidemiology to mechanism and treatment. Clin Interv Aging10, 549–560.
24.
Sanchez-EspinosaMP, AtienzaM, CanteroJL (2014) Sleep deficits in mild cognitive impairment are related to increased levels of plasma amyloid-beta and cortical thinning. Neuroimage98, 395–404.
25.
PratherAA, PutermanE, LinJ, O’DonovanA, KraussJ, TomiyamaAJ, EpelES, BlackburnEH (2011) Shorter leukocyte telomere length in midlife women with poor sleep quality. J Aging Res2011, 721390.
26.
SpiraAP, Chen-EdinboroLP, WuMN, YaffeK (2014) Impact of sleep on the risk of cognitive decline and dementia. Curr Opin Psychiatry27, 478–483.
27.
PiccinniA, OrigliaN, VeltriA, VizzaccaroC, MarazzitiD, VanelliF, MoroniI, DomeniciL, Dell’OssoL (2013) Neurodegeneration, β-amyloid and mood disorders: State of the art and future perspectives. Int J Geriatr Psychiatry28, 661–671.
DengW, CheungST, TsaoSW, WangXM, TiwariAFY (2016) Telomerase activity and its association with psychological stress, mental disorders, lifestyle factors and interventions: A systematic review. Psychoneuroen-docrinology64, 150–163.
30.
BrownBM, PeifferJJ, TaddeiK, LuiJK, LawsSM, GuptaVB, TaddeiT, WardVK, RodriguesMA, BurnhamS, Rainey-SmithSR, VillemagneVL, BushA, EllisKA, MastersCL, AmesD, MacaulaySL, SzoekeC, RoweCC, MartinsRN (2013) Physical activity and amyloid-beta plasma and brain levels: Results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing. Mol Psychiatry18, 875–881.
31.
FyhrquistFY, SaijonmaaOJ (2016) Modifiable factors influencing telomere length and aging. In Inflammation, Aging, and Oxidative Stress,
BondySC, CampbellA eds. Springer, Switzerland, pp. 67–80.
32.
SchutteNS, MalouffJM (2014) A meta-analytic review of the effects of mindfulness meditation on telomerase activity. Psychoneuroendocrinology42, 45–48.
33.
ArsenisNC, YouT, OgawaEF, TinsleyGM, ZuoL (2017) Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget8, 45008–45019.
CraftS (2009) The role of metabolic disorders in Alzheimer disease and vascular dementia: Two roads converged. Arch Neurol66, 300–305.
36.
AshtonNJ, HyeA, LeckeyCA, JonesAR, GardnerA, ElliottC, WetherellJL, LenzeEJ, KillickR, MarchantNL (2017) Plasma REST: A novel candidate biomarker of Alzheimer’s disease is modified by psychological intervention in an at-risk population. Transl Psychiatry7e1148.
37.
InnesK, SelfeT, KhalsaD, KandatiSA (2016) Randomized controlled trial of two simple mind-body pro Kirtan Kriya meditation and music listening, for adults with cognitive decline: Feasibility and acceptability. Compl TherMed26, 98–107.
38.
AbdulrabK, HeunR (2008) Subjective memory impairment. A review of its definitions indicates the need for a comprehensive set of standardised and validated criteria. Eur Psychiatry23, 321–330.
39.
ReisbergB, PrichepL, MosconiL, JohnER, Glodzik-SobanskaL, BoksayI, MonteiroI, TorossianC, VedvyasA, AshrafN, JamilIA, de LeonMJ (2008) The pre-mild cognitive impairment, subjective cognitive impairment stage of Alzheimer’s disease. Alzheimers Dement4, S98–S108.
40.
JessenF, WieseB, BachmannC, Eifflaender-GorferS, HallerF, KolschH, LuckT, MoschE, van den BusscheH, WagnerM, WollnyA, ZimmermannT, PentzekM, RiedelHellerSG, RombergHP, WeyererS, KaduszkiewiczH, MaierW, BickelH (2010) Prediction of dementia by subjective memory impairment: Effects of severity and temporal association with cognitive impairment. Arch Gen Psychiatry67, 414–422.
41.
JessenF, SteffenWolfsgruber, WieseB, BickeldH, MoschE, KaduszkiewiczH, PentzekM, Riedel-HellerSG, LuckT, FuchsA, WeyererS, WerleJ, Buss-cheHvd, SchererM, MaierW, WagnerM (2014) AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement10, 76–83.
42.
KopparaA, WagnerM, LangeC, ErnstA, WieseB, KönigH-H, BrettschneiderC, Riedel-HellerS, LuppaM, WeyererS, WerlJ, BickelH, MoschE, PentzekM, FuchsA, WolfsgruberS, BeauducelA, SchererM, MaierW, JessenF (2015) Cognitive performance before and after the onset of subjective cognitive decline in old age Alzheimers Dement1, 194–205.
43.
GilewskiMJ, ZelinskiEM, SchaieKW (1990) The Memory Functioning Questionnaire for assessment of memory complaints in adulthood and old age. Psychol Aging5, 482–490.
44.
ReitanRM (1958) Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills8, 271–276.
BergerBG, MotlRW (2000) Exercise and mood: A selective review and synthesis of research employing the Profile of Mood States. / Exercice et humeur: Une revue et synthese selective de la recherche sur les profils des etats d’humeur. J Appl Sport Psychol12, 69–92.
47.
RyffCD, KeyesCL (1995) The structure of psychological well-being revisited. J Pers Soc Psychol69, 719–727.
48.
CohenS, KamarckT, MermelsteinR (1983) A global measure of perceived stress. J Health Soc Behav24, 385–396.
49.
CohenS (1988) Perceived stress in a probability sample the United States. In The social psychology of health, SpacapanS, OskampS eds. Sage Publications, Thousand Oaks, pp. 31–67.
50.
BuysseDJ, ReynoldsCF3rd, MonkTH, BermanSR, KupferDJ (1989) The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Res28, 193–213.
51.
DevillyGJ, BorkovecTD (2000) Psychometric properties of the credibility/expectancy questionnaire. J Behav Ther Exp Psychiatry31, 73–86.
52.
InnesKE, SelfeTK, BrownC, RoseK, Thompson-HeistermanA (2012) The effects of meditation on perceived stress and related indices of psychological status and sympathetic activation in persons with Alzheimer’s disease and their caregivers: A pilot study. Evid Based Complement Alternat Med2012, 9.
53.
DiBenedettoM, InnesKE, TaylorAG, RodeheaverPF, BoxerJA, WrightHJ, KerriganDC (2005) Effect of a gentle I¥gar yoga program on gait in the elderly: An exploratory study. Arch Phys Med Rehabil86, 1830–1837.
54.
VickersAJ (2006) How to randomize. J Soc Integr Oncol4, 194–198.
55.
EckerstromC, OlssonE, KlassonN, BergeJ, NordlundA, BjerkeM, WallinA (2015) Multimodal prediction of dementia with up to 10 years follow up: The Gothenburg MCI Study. J Alzheimers Dis44, 205–214.
56.
RappS, BrenesG, MarshAP (2002) Memory enhancement training for older adults with mild cognitive impairment: A preliminary study. Aging Ment Health6, 5–11.
57.
ZelinskiEM, GilewskiMJ, AnthonybergstoneCR (1990) Memory Functioning Questionnaire - concurrent validity with memory performance and self-reported memory failures. Psychol Aging5, 388–399.
58.
InnesK, SelfeT, KhalsaD, KandatiSA (2016) Effects of meditation vs. music listening on perceived stress, mood, sleep and quality of life in adults with early memory loss: A pilot randomized controlled trial. J Alzheimers Dis52, 1277–1298.
59.
EpelES, PutermanE, LinJ, BlackburnEH, LumPY, BeckmannND, ZhuJ, LeeE, GilbertA, RissmanRA, TanziRE, SchadtEE (2016) Meditation and vacation effects have an impact on disease-associated molecular phenotypes. Transl Psychiatry6, e880.
60.
BakerLD, FrankLL, Foster-SchubertK, GreenPS, WilkinsonCW, McTiernanA, PlymateSR, FishelMA, WatsonGS, CholertonBA, DuncanGE, MehtaPD, CraftS (2010) Effects of aerobic exercise on mild cognitive impairment: A controlled trial. Arch Neurol67, 71–79.
61.
LaiR, LogovinskyV, KaplowJM, GuK, YuY, MollerC, NaviaB, SwansonC, LannfeltL, SatlinA (2013) A first-in-human study of BAN2401, a novel monoclonal antibody against beta-amyloid protofibrils. Alzheimers Dement9, P689.
62.
DoodyRS, ThomasRG, FarlowM, IwatsuboT, VellasB, JoffeS, KieburtzK, RamanR, SunX, AisenPS, SiemersE, Liu-SeifertH, MohsR, Alzheimer’s Disease Cooperative Study Steering Committee; Solanezumab Study Group (2014) Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med370, 311–321.
SiemersER, FriedrichS, DeanRA, GonzalesCR, FarlowMR, PaulSM, DemattosRB (2010) Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol33, 67–73.
65.
SiemersE (2009) Biochemical biomarkers as endpoints in clinical trials: Applications in phase 1, 2 and 3 studies. Alzheimers Dement5, P95.
GiedraitisV, SundelofJ, IrizarryMC, GarevikN, HymanBT, WahlundL-O, IngelssonM, LannfeltL (2007) The normal equilibrium between CSF and plasma amyloid beta levels is disrupted in Alzheimer’s disease. Neurosci Lett427, 127–131.
68.
AmariglioRE, BeckerJA, CarmasinJ, WadsworthLP, LoriusN, SullivanC, MayeJE, GidicsinC, PepinLC, SperlingRA, JohnsonKA, RentzDM (2012) Subjective cognitive complaints and amyloid burden in cognitively normal older individuals. Neuropsychologia50, 2880–2886.
69.
SnitzBE, WeissfeldLA, CohenAD, LopezOL, NebesRD, AizensteinHJ, McDadeE, PriceJC, MathisCA, KlunkWE (2015) Subjective cognitive complaints, personality and brain amyloid-beta in cognitively normal older adults. Am J Geriatr Psychiatry23, 985–993.
70.
RentzDM, LocascioJJ, BeckerJA, MoranEK, EngE, BucknerRL, SperlingRA, JohnsonKA (2010) Cognition, reserve, and amyloid deposition in normal aging. Ann Neurol67, 353–364.
71.
RodrigueKM, KennedyKM, DevousMDSr, RieckJR, HebrankAC, Diaz-ArrastiaR, MathewsD, ParkDC (2012) beta-Amyloid burden in healthy aging: Regional distribution and cognitive consequences. Neurology78, 387–395.
72.
PikeKE, SavageG, VillemagneVL, NgS, MossSA, MaruffP, MathisCA, KlunkWE, MastersCL, RoweCC (2007) Beta-amyloid imaging and memory in non-demented individuals: Evidence for preclinical Alzheimer’s disease. Brain130, 2837–2844.
73.
SnitzBE, WeissfeldLA, LopezOL, KullerLH, SaxtonJ, SinghabahuDM, KlunkWE, MathisCA, PriceJC, IvesDG, CohenAD, McDadeE, DekoskyST (2013) Cognitive trajectories associated with beta-amyloid deposition in the oldest-old without dementia. Neurology80, 1378–1384.
74.
RegerMA, WatsonGS, GreenPS, WilkinsonCW, BakerLD, CholertonB, FishelMA, PlymateSR, BreitnerJCS, DeGroodtW, MehtaP, CraftS (2008) Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology70, 440–448.
75.
WatsonGS, CholertonBA, RegerMA, BakerLD, Ply-mateSR, AsthanaS, FishelMA, KulstadJJ, GreenPS, CookDG, KahnSE, KeelingML, CraftS (2005) Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: A preliminary study. Am J Geriatr Psychiatry13, 950–958.
ShiL, ChenS-J, MaM-Y, BaoY-P, HanY, WangY-M, ShiJ, VitielloMV, LuL (2017) Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis. Sleep Med Rev40, 4–16.
79.
BrownBM, Rainey-SmithSR, BucksRS, WeinbornM, MartinsRN (2016) Exploring the bi-directional relationship between sleep and beta-amyloid. Curr Opin Psychiatry29, 397–401.
80.
Tarasoff-ConwayJM, CarareRO, OsorioRS, GlodzikL, ButlerT, FieremansE, AxelL, RusinekH, NicholsonC, ZlokovicBV, FrangioneB, BlennowK, MenardJ, ZetterbergH, WisniewskiT, de LeonMJ (2015) Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol11, 457–470.
81.
MendelsohnAR, LarrickJW (2013) Sleep facilitates clearance of metabolites from the brain: Glymphatic function in aging and neurodegenerative diseases. Rejuvenation Res16, 518–523.
82.
JessenNA, MunkASF, LundgaardI, NedergaardM (2015) The glymphatic system: A beginner’s guide. Neurochem Res40, 2583–2599.
InnesK, SelfeT, KhalsaD, KandatiS (2017) Meditation and music improve cognition in adults with subjective cognitive decline. A preliminary randomized controlled trial. J Alzheimers Dis56.
85.
DonovanNJ, AmariglioRE, ZollerAS, RudelRK, Gomez-IslaT, BlackerD, HymanBT, LocascioJJ, JohnsonKA, SperlingRA, MarshallGA, RentzDM (2014) Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease. Am J Geriatr Psychiatry22, 1642–1651.
86.
WilsonRS, SchneiderJA, BoylePA, ArnoldSE, TangY, BennettDA (2007) Chronic distress and incidence of mild cognitive impairment. Neurology68, 2085–2092.
87.
AggarwalNT, WilsonRS, BeckTL, RajanKB, LeonCFMd, EvansDA, Everson-RoseSA (2014) Perceived stress and change in cognitive function among adults aged 65 and older. Psychosom Med76, 80–85.
88.
GaoY, HuangC, ZhaoK, MaL, QiuX, ZhangL, XiuY, ChenL, LuW, HuangC, TangY, XiaoQ (2013) Depression as a risk factor for dementia and mild cognitive impairment: A meta-analysis of longitudinal studies. Int J Geriatr Psychiatry28, 441–449.
89.
BarnesDE, YaffeK (2011) The projected effect of riskfac-tor reduction on Alzheimer’s disease prevalence. Lancet Neurol10,819–828.
90.
VerdelhoA, MadureiraS, MoleiroC, FerroJM, O’BrienJT, PoggesiA, PantoniL, FazekasF, ScheltensP, WaldemarG, WallinA, ErkinjunttiT, InzitariD (2013) Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: The LADIS study. J Neurol Neurosurg Psychiatry84, 1250–1254.
91.
DinizBS, ButtersMA, AlbertSM, DewMA, ReynoldsCF3rd (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 Psychiatry202, 329–335.
92.
GallacherJ, BayerA, FishM, PickeringJ, PedroS, DunstanF, EbrarimS, Ben-ShlomoY (2009) Does anxiety affect risk of dementia? Findings from the Caerphilly Prospective Study. Psychosom Med71, 659–666.
93.
WilsonRS, BegenyCT, BoylePA, SchneiderJA, BennettDA (2011) Vulnerability to stress, anxiety, and develi ment of dementia in old age. Am J Geriatr Psychiatry327–334.
94.
ReisbergB, ShulmanMB, TorossianC, LengL, ZhuW (2010) Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimers Dement6, 11–24.
95.
SinoffG, WernerP (2003) Anxiety disorder and accompanying subjective memory loss in the elderly as a predictor of future cognitive decline. Int J Geriatr Psychiatry18, 951–959.
96.
PotvinO, ForgetH, GrenierS, PrevilleM, HudonC (2011) Anxiety, depression, and 1-year incident cognitive impairment in community-dwelling older adults. J Am Geriatr Soc59, 1421–1428.
97.
ZandiT (2004) Relationship between subjective memory complaints, objective memory performance, and depression among older adults. Am J Alzheimers Dis Other Demen19, 353–360.
98.
MolM, CarpayM, RamakersI, RozendaalN, VerheyF, JollesJ (2007) The effect of perceived forgetfulness on quality of life in older adults; a qualitative review. Int J Geriatr Psychiatry22, 393–400.
99.
MontejoP, MontenegroM, FernandezMA, MaestuF (2011) Subjective memory complaints in the elderly: Prevalence and influence of temporal orientation, depression and quality of life in a population-based study in the city of Madrid. Aging Ment Health15, 85–96.
100.
HarringtonKD, LimYY, GouldE, MaruffP (2015) Amyloid-beta and depression in healthy older adults: A systematic review. Aust N Z J Psychiatry49, 36–46.
101.
ToledoJB, ShawLM, TrojanowskiJQ (2013) Plasma amyloid beta measurements - a desired but elusive Alzheimer’s disease biomarker. Alzheimers Res Ther5, 8.
102.
SundelofJ, GiedraitisV, IrizarryMC, SundstromJ, Ingels-sonE, RonnemaaE, ArnlovJ, GunnarssonMD, HymanBT, BasunH, IngelssonM, LannfeltL, KilanderL (2008) Plasma beta amyloid and the risk of Alzheimer disease and dementia in elderly men: A prospective, population-based cohort study. Arch Neurol65, 256–263.
103.
ShahNS, VidalJS, MasakiK, PetrovitchH, RossGW, TilleyC, DeMattosRB, TracyRP, WhiteLR, LaunerLJ (2012) Midlife blood pressure, plasma beta-amyloid, and the risk for Alzheimer disease: The Honolulu Asia Aging Study. Hypertension59, 780–786.
104.
KaffashianS, TzourioC, SoumareA, DufouilC, MazoyerB, Schraen-MaschkeS, BueeL, DebetteS (2015) Association of plasma beta-amyloid with MRI markers of structural brain aging the 3-City Dijon study. Neurobiol Aging36, 2663–2670.
105.
StillmanCM, LopezOL, BeckerJT, KullerLH, MehtaPD, TracyRP, EricksonKI (2017) Physical activity predicts reduced plasma beta amyloid in the Cardiovascular Health Study. Ann Clin Transl Neurol4, 284–291.
106.
HanssonO, ZetterbergH, VanmechelenE, VandersticheleH, AndreassonU, LondosE, WallinA, MinthonL, BlennowK (2010) Evaluation of plasma Aβ40 and Aβ42 as predictors of conversion to Alzheimer’s disease in patients with mild cognitive impairment. Neurobiol Aging31, 357–367.
107.
PoljakA, CrawfordJD, SmytheGA, BrodatyH, SlavinMJ, KochanNA, TrollorJN, WenW, MatherKA, AssarehAA, NgPC, SachdevPS (2016) The relationship between plasma Abeta levels, cognitive function and brain volumet-rics: Sydney Memory and Ageing Study. Curr Alzheimer Res13, 243–255.
108.
ToledoJB, VandersticheleH, FigurskiM, AisenPS, PetersenRC, WeinerMW, JackCR, JagustW, DecarliC, TogaAW (2011) Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI. Acta Neuropathol (Berl)122, 401.
109.
RobertsKF, ElbertDL, KastenTP, PattersonBW, Sigurd-sonWC, ConnorsRE, OvodV, MunsellLY, MawuenyegaKG, Miller-ThomasMM, MoranCJ, CrossDT3rd, DerdeynCP, BatemanRJ (2014) Amyloid-β efflux from the central nervous system into the plasma. Ann Neurol76, 837–844.
110.
JanelidzeS, StomrudE, PalmqvistS, ZetterbergH, van WestenD, JerominA, SongL, HanlonD, Tan HehirCA, BakerD, BlennowK, HanssonO (2016) Plasma beta-amyloid in Alzheimer’s disease and vascular disease. Sci Rep6, 26801.
111.
BlackburnEH (1991) Structure and function of telomeres. Nature350, 569–573.
112.
BroccoliD (2004) Function, replication and structure of the mammalian telomere. Cytotechnology45, 3–12.
113.
MatherKA, JormAF, ParslowRA, ChristensenH (2011) Is telomere length a biomarker of aging? A review. J Gerontol A Biol Sci Med Sci66, 202–213.
114.
D’MelloMJ, RossSA, BrielM, AnandSS, GersteinH, PareG (2014) The association between shortened leukocyte telomere length and cardio-metabolic outcomes: A systematic review and meta-analysis. Circ Genom Precis Med8, 82–90.
115.
VerhoevenJE, ReveszD, EpelES, LinJ, WolkowitzOM, PenninxBWJH (2014) Major depressive disorder and accelerated cellular aging: Results from a large psychiatric cohort study. Mol Psychiatry19, 895–901.
116.
EpelES, MerkinSS, CawthonR, BlackburnEH, AdlerNE, PletcherMJ, SeemanTE (2009) The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly men. Aging1, 81–88.
117.
EitanE, HutchisonER, MattsonMP (2014) Telomere shortening in neurological disorders: An abundance of unanswered questions. Trends Neurosci37, 256–263.
118.
BoccardiV, PeliniL, ErcolaniS, RuggieroC, MecocciP (2015) From cellular senescence to Alzheimer’s disease: The role of telomere shortening. Ageing Res Rev22, 1–8.
119.
Moverare-SkrticS, JohanssonP, MattssonN, HanssonO, WallinA, JohanssonJ-O, ZetterbergH, BlennowK, SvenssonJ (2012) Leukocyte telomere length (LTL) is reduced in stable mild cognitive impairment but low LTL is not associated with conversion to Alzheimer’s disease: A pilot study. Exp Gerontol47, 179–182.
120.
ZekryD, HerrmannFR, Irminger-FingerI, OrtolanL, GenetC, VitaleA-M, MichelJ-P, GoldG, KrauseK-H (2010) Telomere length is not predictive of dementia or MCI conversion in the oldest old. Neurobiol Aging31, 719–720.
121.
GrodsteinF, van OijenM, IrizarryMC, RosasHD, HymanBT, GrowdonJH, De VivoI (2008) Shorter telomeres may mark early risk of dementia: Preliminary analysis of 62 participants from the Nurses’ Health Study. PLoS One3, e1590.
122.
WikgrenM, KarlssonT, LindJ, NilbrinkT, HultdinJ, SleegersK, Van BroeckhovenC, RoosG, Nils-sonL-G, NybergL (2012) Longer leukocyte telomere length is associated with smaller hippocampal volume among non-demented APOE e3/e3 subjects. PLoS One7, e34292.
123.
EpelES, LinJ, DhabharFS, WolkowitzOM, PutermanE, KaranL, BlackburnEH (2010) Dynamics of telomerase activity in response to acute psychological stress. Brain Behav Immun24, 531–539.
124.
CarlsonLE, BeattieTL, Giese-DavisJ, FarisP, TamagawaR, FickLJ, DegelmanES, SpecaM (2015) Mindfulness-based cancer recovery and supportive-expressive therapy maintain telomere length relative to controls in distressed breast cancer survivors. Cancer121, 476–484.
125.
LengacherCA, ReichRR, KipKE, BartaM, RamesarS, PatersonCL, MoscosoMS, CarranzaI, BudhraniPH, KimSJ, ParkHY, JacobsenPB, SchellMJ, JimHSL, Post-WhiteJ, FariasJR, ParkJY (2014) Influence of mindfulness-based stress reduction (MBSR) on telom-erase activity in women with breast cancer (BC). Biol Res Nurs16, 438–447.
126.
DaubenmierJ, LinJ, BlackburnE, HechtFM, KristellerJ, ManingerN, KuwataM, BacchettiP, HavelPJ, EpelE (2012) Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psy-choneuroendocrinology37, 917–928.
127.
DuraimaniS, SchneiderRH, RandallOS, NidichSI, XuS, KeteteM, RainforthMA, Gaylord-KingC, SalernoJW, FaganJ (2015) Effects of lifestyle modification on telom-erase gene expression in hypertensive patients: A pilot trial of stress reduction and health education programs in African Americans. PLoS One10, e0142689.
128.
LavretskyH, EpelES, SiddarthP, NazarianN, CyrNS, KhalsaDS, LinJ, BlackburnE, IrwinMR (2013) A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: Effects on mental health, cognition, and telomerase activity. Int J Geriatr Psychiatry28, 57–65.
129.
HoRT, ChanJS, WangCW, LauBW, SoKF, YuenLP, ShamJS, ChanCL (2012) A randomized controlled trial of qigong exercise on fatigue symptoms, functioning, and telomerase activity in persons with chronic fatigue or chronic fatigue syndrome. Ann Behav Med44, 160–170.
130.
DuanGX, WangK, SuYH, TangSY, JiaHL, ChenXM, XieHH (2016) Effects of Tai Chi on telomerase activity and gerotranscendence in middle aged and elderly adults in Chinese society. Int J Nurs Sci3, 235–241.
131.
LuckT, Riedel-HellerSG, LuppaM, WieseB, BachmannC, JessenF, BickelH, WeyererS, PentzekM, KonigHH, ProkeinJ, EiseleM, WagnerM, MoschE, WerleJ, FuchsA, BrettschneiderC, SchererM, BreitnerJC, MaierW (2014) A hierarchy of predictors for dementia-free survival in old-age: Results of the AgeCoDe study. Acta Psychiatr Scand129, 63–72.
132.
FonsecaJ, DucksburyR, RoddaJ (2015) Factors that predict cognitive decline in patients with subjective cognitive impairment. Int Psychogeriatr27, 1671–1677.
133.
LueL-F, GuerraA, WalkerDG (2017) Amyloid beta and tau as Alzheimer’s disease blood biomarkers: Promise from new technologies. Neurol Ther6, 25–36.
134.
MielkeMM, HaugheyNJ, BandaruVVR, ZetterbergH, BlennowK, AndreassonU, JohnsonSC, GleasonCE, BlazelHM, PuglielliL, SagerMA, AsthanaS, CarlssonCM (2014) Cerebrospinal fluid sphingolipids, beta-amyloid, and tau in adults at risk for Alzheimer’s disease. Neurobiol Aging35, 2486–2494.
135.
PanC, KorffA, GalaskoD, GinghinaC, PeskindE, LiG, QuinnJ, MontineTJ, CainK, ShiM, ZhangJ (2015) Diagnostic values of cerebrospinal fluid t-tau and Aβ42 using Meso Scale Discovery assays for Alzheimer’s disease. J Alzheimers Dis45, 709–719.
136.
HoglundK, KernS, ZettergrenA, Borjesson-HanssonA, ZetterbergH, SkoogI, BlennowK (2017) Preclinical amyloid pathology biomarker positivity: Effects on tau pathology and neurodegeneration. Transl Psychiatry7, e995.
137.
DabitaoD, MargolickJB, LopezJ, BreamJH (2011) Multiplex measurement of proinflammatory cytokines in human serum: Comparison of the Meso Scale Discovery electrochemiluminescence assay and the Cytometric Bead Array. J Immunol Methods372, 71–77.
MichellB, SambuchiN, GedaY, MuraccioliI, PabanV, JouveE, SambucR, ChenH-M, BartolinA, GallantC, JeanJ-CS, RouyerC, BrossetC, AzorinJ-M, Alescio-LautierB, PetersenR (2014) Subjective cognitive impairment in a french sample. Neurol Clin Neurophysiol82, P2.174.
140.
RonnlundM, SundstromA, AdolfssonR, NilssonL-G (2015) Subjective memory impairment in older adults predicts future dementia independent of baseline memory performance: Evidence from the Betula prospective cohort study. Alzheimers Dement11, 1385–1392.
141.
Garcia-PtacekS, EriksdotterM, JelicV, Porta-EtessamJ, KareholtI, Manzano PalomoS (2016) Subjective cognitive impairment: Towards early identification of Alzheimer disease. Neurologia31, 562–571.
142.
BuckleyRF, RoweCC, DoreV, LawsSM, BourgeatP, BurnhamS, SalvadoO, MaruffP, MacaulaySL, MartinsRN (2016) Mesial temporal tau burden in older adults with subjective memory complaints relates to poorer memory function. Alzheimers Dement12, P344–P345.
143.
van HartenAC, MielkeMM, Swenson-DravisDM, HagenCE, EdwardsKK, RobertsRO, GedaYE, KnopmanDS, PetersenRC (2018) Subjective cognitive decline and risk of MCI: The Mayo Clinic Study of Aging. Neurology91, e300–e312.
144.
Jacqmin-GaddaH, BlancheP, CharyE, LoubereL, AmievaH, DartiguesJF (2014) Prognostic score for predicting risk of dementia over 10 years while accounting for competing risk of death. Am J Epidemiol180,790–798.
145.
BaudouinA, ClarysD, VannesteS, IsingriniM (2009) Executive functioning and processing speed in age-related differences in memory: Contribution of a coding task. Brain Cogn71, 240–245.
146.
KinserPA, RobinsJL (2013) Control group design: Enhancing rigor in research of mind-body therapies for depression. Evid Based Complement Alternat Med2013140467.
147.
ImtiazB, TolppanenAM, KivipeltoM, SoininenH (2014) Future directions in Alzheimer’s disease from risk factors to prevention. Biochem Pharmacol88, 661–670.
