Background: Neuropsychiatric symptoms (NPS) are common in older adults with cognitive impairment, yet little is known about population-based prevalence and clinical implications of co-morbid symptom presentation across the spectrum from normal cognition to dementia.
Objective: To characterize the prevalence of NPS and explore the clinical implications of co-morbid symptom presentation.
Methods: Cross-sectional study of 1,417 older adults (aged 73–79) with dementia (n = 40); with mild cognitive impairment (MCI; n = 133); who are ‘cognitively normal, but-at-risk’ (CN-AR; n = 397); and who are cognitively normal (n = 847). NPS were assessed by the Neuropsychiatric Inventory. Cluster analyses were conducted using a latent class analysis (LCA).
Results: NPS are highly prevalent across the cognitive function spectrum (30.8% –80%). NPS were associated with a 3-fold increased risk of dementia, a 2-fold increased risk of MCI, and a 1.5-times increased risk of CN-AR. Each additional co-morbid symptom was associated with an additional 1.5-times increased risk of dementia, but not MCI or CN-AR. LCA revealed four distinctive sub-populations: 1) frontal/low comorbidity; 2) high prevalence/high comorbidity; 3) affective/low comorbidity; and 4) sleep/low comorbidity.
Conclusion: Our findings confirm previous reports on the prevalence of NPS in community-based samples and are consistent with the profiles of NPS domain characteristics of MCI and dementia. Number of co-morbid NPS and not symptom clusters are associated with increased risk of dementia. Understanding such patterns will help inform our understanding of mild behavioral disorders and assist with clinical assessment.
CerejeiraJ, LagartoL, Mukaetova-LadinskaEB (2012) Behavioral and psychological symptoms of dementia. Front Neurol3, 73.
3.
GitlinLN, PiersolCV, HodgsonN, MarxK, RothDL, JohnstonD, SamusQ, PizziL, JutkowitzE, LyketsosCG (2016) Reducing neuropsychiatric symptoms in persons with dementia and associated burden in family caregivers using tailored activities: Design and methods of a randomized clinical trial. Contemp Clin Trials49, 92–102.
4.
PetersME, RosenbergP, SteinbergM, TschanzJ, NortonMC, Welsh-BohmerKA, HaydenKM, BreitnerJCS, LyketsosCG, The Cache County Investigators (2012) Prevalence of neuropsychiatric symptoms in CIND and its subtypes: The cache county study. Am J Geriatr Psychiatry20, 416–424.
5.
GedaYE, RobertsRO, KnopmanDS, PetersenRC, ChristiansonTJ, PankratzVS, SmithGE, BoeveBF, IvnikRJ, TangalosEG, RoccaWA (2008) Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: Population-based study. Arch Gen Psychiatry65, 1193–1198.
6.
IsmailZ, ElbayoumiH, FischerCE, HoganDB, MillikinCP, SchweizerT, MortbyME, SmithEE, PattenSB, FiestKM (2017) Prevalence of depression in patients with mild cognitive impairment: A systematic review and meta-analysis. JAMA Psychiatry74, 58–67.
7.
SteinbergM, ShaoH, ZandiP, LyketsosC, Welsh-BohmerK, NortonM (2008) Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: The Cache County Study. Int J Geriatr Psychiatry23, 170–177.
8.
LyketsosCG, LopezO, JonesB, FitzpatrickAL, BreitnerJ, DeKoskyS (2002) Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: Results from the cardiovascular health study. JAMA288, 1475–1483.
9.
PetersME, RosenbergPB, SteinbergM, NortonMC, Welsh-BohmerKA, HaydenKM, BreitnerJ, TschanzJT, CgL, the Cache County Investigators (2013) Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: The Cache County Study. Am J Geriatr Psychiatry21, 1116–1124.
10.
PinkA, StokinGB, BartleyMM, RobertsRO, SochorO, MachuldaMM, Krell-RoeschJ, KnopmanDS, AcostaJI, ChristiansonTJ, PankratzVS, MielkeMM, PetersenRC, GedaYE (2015) Neuropsychiatric symptoms, APOE epsilon4, and the risk of incident dementia: A population-based study. Neurology84, 935–943.
11.
RosenbergPB, MielkeMM, ApplebyBS, OhES, GedaYE, LyketsosCG (2013) The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease. Am J Geriatr Psychiatry21, 685–695.
12.
BrodatyH, ConnorsMH, XuJ, WoodwardM, AmesD (2014) Predictors of institutionalization in dementia: A three year longitudinal study. J Alzheimers Dis40, 221–226.
13.
GanguliM, DodgeHH, ShenC, PandavRS, DeKoskyST (2005) Alzheimer disease and mortality: A 15-year epidemiological study. Arch Neurol62, 779–784.
TaraganoF, AllegriR, KrupitzkiH, SarasolaD, SerranoC, LonL (2009) Mild behavioral impairment and risk of dementia: A prospective cohort study of 358 patients. J Clin Psychiatry70, 584–592.
16.
RabinsPV, SchwartzS, BlackBS, CorcoranC, FauthE, MielkeM, ChristensenJ, LyketsosC, TschanzJ (2013) Predictors of progression to severe Alzheimer’s disease in an incidence sample. Alzheimers Dement9, 204–207.
17.
NowrangiM, LyketsosC, RosenbergP (2015) Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia. Alzheimers Res Ther7, 12.
18.
CanevelliM, AdaliN, VoisinT, SotoM, BrunoG, CesariM (2013) Behavioral and psychological subsyndromes in Alzheimer’s disease using the Neuropsychiatric Inventory. Int J Geriatr Psychiatry28, 795–803.
19.
ForresterSN, GalloJJ, SmithGS, LeoutsakosJM (2016) Patterns of neuropsychiatric symptoms in mild cognitive impairment and risk of dementia. Am J Geriatr Psychiatry24, 117–125.
20.
MortbyME, AnsteyKJ (2015) Mental health and aging. In Encyclopedia of Geropsychology, PachanaAN, ed. Springer Singapore, Singapore, pp. 1–6.
21.
GedaYE, RobertsRO, MielkeMM, KnopmanDS, ChristiansonTJ, PankratzVS, BoeveBF, SochorO, TangalosEG, PetersenRC, RoccaWA (2014) Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: A population-based study. Am J Psychiatry171, 572–581.
22.
IsmailZ, SmithEE, GedaY, SultzerD, BrodatyH, SmithG, Aguera-OrtizL, SweetR, MillerD, LyketsosCG (2016) Neuropsychiatric symptoms as early manifestations of emergentdementia: Provisional diagnostic criteria for mild behavioralimpairment. Alzheimers Dement12, 195–202.
23.
Di IulioF, PalmerK, BlundoC, CasiniAR, GianniW, CaltagironeC, SpallettaG (2010) Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer’s disease and mild cognitive impairment subtypes. Int Psychogeriatr22, 629–640.
24.
EdwardsER, SpiraAP, BarnesDE, YaffeK (2009) Neuropsychiatric symptoms in mild cognitive impairment: Differences by subtype and progression to dementia. Int J Geriatr Psychiatry24, 716–722.
25.
RosenbergPB, MielkeMM, ApplebyB, OhE, LeoutsakosJM, LyketsosCG (2011) Neuropsychiatric symptoms in MCI subtypes: The importance of executive dysfunction. Int J Geriatr Psychiatry26, 364–372.
26.
LyketsosCG, SteinbergM, TschanzJT, NortonMC, SteffensDC, BreitnerJC (2000) Mental and behavioral disturbances in dementia: Findings from the Cache County Study on Memory in Aging. Am J Psychiatry157, 708–714.
27.
IsmailZ, Aguera-OrtizL, BrodatyH, CieslakA, CummingsJ, FisherC, GauthierS, GedaY, HerrmannN, KanjiJ, LanctôtKL, MillerD, MortbyME, OnyikeCU, RosenbergP, SmithEE, SmithG, SultzerD, LyketsosC (2017) The Mild Behavioral Impairment Checklist (MBI-C): A rating scale for neuropsychiatric symptoms in pre-dementia populations. J Alzheimers Dis56, 929–938.
28.
GallagherD, FischerCE, IaboniA (2017) Neuropsychiatric symptoms in mild cognitive impairment. Can J Psychiatry62, 161–169.
29.
AnsteyKJ, ChristensenH, ButterworthP, EastealS, MackinnonA, JacombT, MaxwellK, RodgersB, WindsorT, CherbuinN, JormAF (2012) Cohort Profile: The PATH through life project. Int J Epidemiol41, 951–960.
30.
EramudugollaR, MortbyME, SachdevP, MeslinC, KumarR, AnsteyKJ (2017) Evaluation of a research diagnostic algorithm for DSM-5 Neurocognitive Disorders in a cohort of adults aged 72-76 years, and comparison with DSM-IV Dementia and MCI diagnoses. Alzheimers Res Ther9, 15.
31.
CrookTH, FeherEP, LarrabeeGJ (1992) Assessment of memory complaint in age-associated memory impairment: The MAC-Q. Int Psychogeriatr4, 165–176.
32.
WinbladB, PalmerK, KivipeltoM, JelicV, FratiglioniL, WahlundLO, NordbergA, BackmanL, AlbertM, AlmkvistO, AraiH, BasunH, BlennowK, de LeonM, DeCarliC, ErkinjunttiT, GiacobiniE, GraffC, HardyJ, JackC, JormA, RitchieK, van DuijnC, VisserP, PetersenRC (2004) Mild cognitive impairment–beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. J Intern Med256, 240–246.
33.
CummingsJL, MegaM, GrayK, Rosenberg-ThompsonS, CarusiDA, GornbeinJ (1994) The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology44, 2308–2314.
34.
SteinbergM, TschanzJT, CorcoranC, SteffensDC, NortonMC, LyketsosCG, BreitnerJC (2004) The persistence of neuropsychiatric symptoms in dementia: The Cache County Study. Int J Geriatr Psychiatry19, 19–26.
35.
van der LindeRM, DeningT, StephanBCM, PrinaAM, EvansE, BrayneC (2016) Longitudinal course of behavioural and psychological symptoms of dementia: Systematic review. Br J Psychiatry209, 366–377.
36.
IsmailZ, MortbyME (2017) Cognitive and neuropsychiatric screening tests in older adults. In Mental Health and Illness of the Elderly, ChiuH, ShulmanK, AmesD, eds. Springer Singapore, Singapore, pp. 1–26.
37.
OkuraT, PlassmanBL, SteffensDC, LlewellynDJ, PotterGG, LangaKM (2010) Prevalence of neuropsychiatric symptoms and their association with functional limitations in older adults in the United States: The aging, demographics, and memory study. J Am Geriatr Soc58, 330–337.
38.
DavidND, LinF, PorsteinssonAP, Initiative AsDN (2016) Trajectories of neuropsychiatric symptoms and cognitive decline in mild cognitive impairment. Am J Geriatr Psychiatry24, 70–80.
39.
ApostolovaLG, CummingsJL (2008) Neuropsychiatric manifestations in mild cognitive impairment: A systematic review of the literature. Dement Geriatr Cogn Disord25, 115–126.
40.
MonasteroR, MangialascheF, CamardaC, ErcolaniS, CamardaR (2009) A systematic review of neuropsychiatric symptoms in mild cognitive impairment. J Alzheimers Dis18, 11–30.
41.
LyketsosCG, SheppardJME, SteinbergM, TschanzJAT, NortonMC, SteffensDC, BreitnerJ (2001) Neuropsychiatric disturbance in Alzheimer’s disease clusters into three groups: The Cache County study. Int J Geriatr Psychiatry16, 1043–1053.
42.
IsmailZ, HerrmannN, FrancisPL, RothenburgLS, LobaughNJ, LeibovitchFS, BlackSE, LanctotKL (2009) A SPECT study of sleep disturbance andAlzheimer’s disease. Dement Geriatr Cogn Disord27, 254–259.
43.
ElwoodPC, BayerAJ, FishM, PickeringJ, MitchellC, GallacherJE (2010) Sleep disturbance and daytime sleepiness predict vascular dementia. J Epidemiol Community Health65, 820–824.
44.
de AlmondesKM, CostaMV, Malloy-DinizLF, DinizBS (2016) Insomnia and risk of dementia in older adults: Systematic review and meta-analysis. J Psychiatr Res77, 109–115.
45.
SrikanthS, NagarajaA, RatnavalliE (2005) Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer’s disease, vascular dementia and frontotemporal dementia. J Neurol Sci236, 43–48.
46.
HornbergerM, GengJ, HodgesJR (2011) Convergent grey and whitematter evidence of orbitofrontal cortex changes related todisinhibition in behavioural variant fronto-temporaldementia. Brain134, 2502–2512.
