The behavioral and psychological symptoms of dementia (BPSD) seriously affect the quality of life of patients with Alzheimer’s disease (AD) and their caregivers.
Objective:
We aimed to identify associations between demographic/genetic factors and clinical presentations of BPSD.
Methods:
In a cohort of 463 AD patients with BPSD, we retrospectively analyzed sex, education level, AD severity (assessed using the Clinical Dementia Rating and Mini-Mental Status Examination), and BPSD severity (assessed using the Neuropsychiatry Inventory, NPI). Severe BPSD was defined as NPI ≥10 for 3 consecutive years.
Results:
Among patients with severe BPSD (NPI ≥10), we observed more female patients (62.96%) and a lower level of education (6.03±4.77 years) as compared to those with mild BPSD (NPI <10) (female: 51.09%, p = 0.007; education years: 7.91±4.93, p < 0.001). Females had a lower level of education (5.72±4.50 years) and higher scores for depression/dysphoria (1.22±2.05) compared with males (education: 8.96±4.89 years, p < 0.001; depression/dysphoria: 0.78±1.42, p = 0.047). Patients with a high level of education (defined as ≥12 years) had higher scores for appetite/eating (0.90±2.02) than did those without (0.69±1.79; p = 0.001). Genetic analysis showed similar total and subscale NPI scores between patients with and without APOE4 and with and without the GRN rs5848 genotype.
Conclusion:
Our findings indicate potential contributions of sex and education to the presentation of BPSD. Further study is warranted to provide models for tailoring therapeutic programs to individual AD patients according to these factors.
QuerfurthHW, LaferlaFM (2010) Alzheimer’s disease. N Engl J Med362, 329–344.
2.
FinkelSI, CostaESilvaJ, CohenG, MillerS, SartoriusN (1996) Behavioral and psychological signs and symptoms of dementia: A consensus statement on current knowledge and implications for research and treatment. Psychogeriatr8 Suppl 3, 497–500.
3.
HuangSS, LeeMC, LiaoYC, WangWF, LaiTJ (2012) Caregiver burden associated with behavioral and psychological symptoms of dementia (BPSD) in Taiwanese elderly. Arch Gerontol Geriatr55, 55–59.
4.
BeeriMS, WernerP, DavidsonM, NoyS (2002) The cost of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Alzheimer’s disease patients. J Geriatr Psychiatry17, 403–408.
5.
TatsumiH, NakaakiS, ToriiK, ShinagawaY, WatanabeN, MurataY, SatoJ, MimuraM, FurukawaTA (2009) Neuropsychiatric symptoms predict change in quality of life of Alzheimer disease patients: A two-year follow-up study. Psychiatry Clin Neurosci63, 374–384.
6.
RyuSH, HaJH, ParkDH, YuJ, LivingstonG (2011) Persistence of neuropsychiatric symptoms over six months in mild cognitive impairment in community-dwelling Korean elderly. Psychogeriatr23, 214–220.
7.
KalesHC, GitlinLN, LyketsosCG (2015) Assessment and management of behavioral and psychological symptoms of dementia. BMJ350, H369.
8.
MegaMS, CummingsJL, FiorelloT, GornbeinJ (1996) The spectrum of behavioral changes in Alzheimer’s disease. Neurology46, 130–135.
9.
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.
10.
SteinbergM, ShaoH, ZandiP, LyketsosCG, Welsh-BohmerKA, NortonMC, BreitnerJC, SteffensDC, TschanzJT, Cache County Investigators (2008) Point And 5-year period prevalence of neuropsychiatric symptoms in dementia: The Cache County Study. J Geriatr Psychiatry23, 170–177.
11.
Van Der LindeRM, DeningT, StephanBC, PrinaAM, EvansE, BrayneC (2016) Longitudinal course of behavioural and psychological symptoms of dementia: Systematic review. Br J Psychiatry209, 366–377.
12.
HueyED, LeeS, CheranG, GrafmanJ, DevanandDP, Alzheimer’s Disease Neuroimaging Initiative (2017) Brain regions involved in arousal and reward processing are associated with apathy in Alzheimer’s disease and frontotemporal dementia. J Alzheimers Dis55, 551–558.
13.
International Psychogeriatric Association (2010) The IPA Complete Guides To Behavioral And Psychological Symptoms Of Dementia. International Psychogeriatric Association, Milwaukee, WI.
14.
LagardeJ, SarazinM, ChauvireV, StankoffB, KasA, LacomblezL, PeyronneauMA, BottlaenderM (2017) Cholinergic changes in aging and Alzheimer disease: An [18F]-F-A-85380 exploratory PET study. Alzheimer Dis Assoc Disord31, 8–12.
15.
MingerSL, EsiriMM, McdonaldB, KeeneJ, CarterJ, HopeT, FrancisPT (2000) Cholinergic deficits contribute to behavioral disturbance in patients with dementia. Neurology55, 1460–1467.
16.
PocnetC, RossierJ, AntoniettiJP, Von GuntenA (2013) Personality traits and behavioral and psychological symptoms in patients at an early stage of Alzheimer’s disease. J Geriatr Psychiatry28, 276–283.
17.
PriorJ, AbrahamR, NicholasH, ChanT, VanvlymenJ, LovestoneS, BoothbyH (2016) Are premorbid abnormal personality traits associated with behavioural and psychological symptoms in dementia?J Geriatr Psychiatry31, 1050–1055.
18.
FeastA, OrrellM, RussellI, CharlesworthG, Moniz-CookE (2017) The contribution of caregiver psychosocial factors to distress associated with behavioural and psychological symptoms in dementia. J Geriatr Psychiatry32, 76–85.
19.
KazuiH, YoshiyamaK, KanemotoH, SuzukiY, SatoS, HashimotoM, IkedaM, TanakaH, HatadaY, MatsushitaM, NishioY, MoriE, TanimukaiS, KomoriK, YoshidaT, ShimizuH, MatsumotoT, MoriT, KashibayashiT, YokoyamaK, ShimomuraT, KabeshitaY, AdachiH, TanakaT (2016) Differences of behavioral and psychological symptoms of dementia in disease severity in four major dementias. One11, E0161092.
20.
LeeJ, LeeKJ, KimH (2017) Gender differences in behavioral and psychological symptoms of patients with Alzheimer’s disease. Asian J Psychiatr26, 124–128.
21.
MckhannGM, KnopmanDS, ChertkowH, HymanBT, JackCRJr., KawasCH, KlunkWE, KoroshetzWJ, ManlyJJ, MayeuxR, MohsRC, MorrisJC, RossorMN, ScheltensP, CarrilloMC, ThiesB, WeintraubS, PhelpsCH (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. Dement7, 263–269.
22.
MorrisJC (1997) Clinical dementia rating: A reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Psychogeriatr9 Suppl 1, 173–176; Discussion 177-178.
23.
FolsteinMF, FolsteinSE, MchughPR (1975) “Mini-Mental State”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res12, 189–198.
24.
CummingsJL, MegaM, GrayK, Rosenberg-ThompsonS, CarusiDA, GornbeinJ (1994) The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology44, 2308–2308.
25.
WenhamPR, PriceWH, BlandellG (1991) Apolipoprotein E genotyping by one-stage PCR. Lancet337, 1158–1159.
26.
PrinceM, AcostaD, FerriCP, GuerraM, HuangY, RodriguezJJL, SalasA, SosaAL, WilliamsJD, DeweyME, AcostaI, JotheeswaranAT, LiuZ (2012) Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: A 10/66 Dementia Research Group population-based cohort study. Lancet380, 50–58.
27.
FratiglioniL, GrutM, ForsellY, ViitanenM, GrafstromM, HolmenK, EricssonK, BackmanL, AhlbomA, WinbladB (1991) Prevalence of Alzheimer’s disease and other dementias in an elderly urban population: Relationship with age, sex, and education. Neurology41, 1886–1892.
28.
ZhangM, KatzmanR, SalmonD, JinH, CaiG, WangZ, QuG, GrantI, YuE, LevyP, KlauberMR, LiuWT (1990) The prevalence of dementia and Alzheimer’s disease in Shanghai, China: Impact of age, gender, and education. Ann Neurol27, 428–437.
29.
KarpA, KåreholtI, QiuC, BellanderT, WinbladB, FratiglioniL (2004) Relation of education and occupation-based socioeconomic status to incident Alzheimer’s disease. Am J Epidemiol159, 175–183.
30.
KatzmanR (1993) Education and the prevalence of dementia and Alzheimer’s disease. Neurology43, 13–20.
CoffeyCE, SaxtonJA, RatcliffG, BryanRN, LuckeJF (1999) Relation of education to brain size in normal aging. Implications for the reserve hypothesis. Neurology53, 189–189.
Arenaza-UrquijoEM, LandeauB, La JoieR, MevelK, MezengeF, PerrotinA, DesgrangesB, Bartres-FazD, EustacheF, ChetelatG (2013) Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders. Neuroimage83, 450–457.
37.
DuraJR, BornsteinRA (1989) Differences between IQ and school achievement in anorexia nervosa. J Clin Psychol45, 433–435.
38.
Bardone-ConeAM, WonderlichSA, FrostRO, BulikCM, MitchellJE, UppalaS, SimonichH (2007) Perfectionism and eating disorders: Current status and future directions. Psychol Rev27, 384–405.
39.
HowlettDR, RichardsonJC, AustinA, ParsonsAA, BateST, DaviesDC, GonzalezMI (2004) Cognitive correlates of Aβ deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. Brain Res1017, 130–136.
40.
BeinhoffU, TumaniH, BrettschneiderJ, BittnerD, RiepeMW (2008) Gender-specificities in Alzheimer’s disease and mild cognitive impairment. J Neurol255, 117–122.
41.
De Pedro-CuestaJ, Virués-OrtegaJ, VegaS, Seijo-MartínezM, SazP, RodríguezF, Rodríguez-LasoA, ReñéR, De Las HerasSP, MateosR, Martínez-MartínP, ManubensJM, Mahillo-FernandezI, López-PousaS, LoboA, ReglàJL, GascónJ, GarcíaFJ, Fernández-MartínezM, BoixR, Bermejo-ParejaF, BergarecheA, Benito-LeónJ, De ArceA, Del BarrioJL (2009) Prevalence of dementia and major dementia subtypes in Spanish populations: A reanalysis of dementia prevalence surveys, 1990-2008. BMC Neurol9, 55.
42.
MaylorEA, ReimersS, ChoiJ, CollaerML, PetersM, SilvermanI (2007) Gender and sexual orientation differences in cognition across adulthood: Age is kinder to women than to men regardless of sexual orientation. Arch Sex Behav36, 235–249.
43.
IrvineK, LawsKR, GaleTM, KondelTK (2012) Greater cognitive deterioration in women than men with Alzheimer’s disease: A meta analysis. J Clin Exp Neuropsychol34, 989–998.
44.
GholizadehS, SadatmahallehSJ, ZiaeiS (2018) The association between estradiol levels and cognitive function in postmenopausal women. J Reprod Biomed (Yazd)16, 455–458.
45.
KitamuraT, KitamuraM, HinoS, TanakaN, KurataK (2012) Gender differences in clinical manifestations and outcomes among hospitalized patients with behavioral and psychological symptoms of dementia. J Clin Psychiatry73, 1548–1554.
46.
LovheimH, SandmanPO, KarlssonS, GustafsonY (2009) Sex differences in the prevalence of behavioral and psychological symptoms of dementia. Psychogeriatr21, 469–475.
47.
HsiehCJ, ChangCC, LinCC (2009) Neuropsychiatric profiles of patients with Alzheimer’s disease and vascular dementia in Taiwan. J Geriatr Psychiatry24, 570–577.
48.
ColomboD, CaltagironeC, PadovaniA, SorbiS, SpallettaG, SimoniL, OriA, ZagniE (2018) Gender differences in neuropsychiatric symptoms in mild to moderate Alzheimer’s disease patients undergoing switch of cholinesterase inhibitors: A post hoc analysis of the EVOLUTION Study. J Women Health (2002)27, 1368–1377.
49.
UllahMF, AhmadA, BhatSH, Abu-DuhierFM, BarretoGE, AshrafGM (2019) Impact of sex differences and gender specificity on behavioral characteristics and pathophysiology of neurodegenerative disorders. Biobehav Rev102, 95–105.
50.
ChenCS, OuyangP, YehYC, LaiCL, LiuCK, YenCF, KoCH, YenJY, LiuGC, JuoSH (2012) Apolipoprotein E polymorphism and behavioral and psychological symptoms of dementia in patients with Alzheimer disease. Alzheimer Dis Assoc Disord26, 135–139.
51.
XuHM, TanL, WanY, TanMS, ZhangW, ZhengZJ, KongLL, WangZX, JiangT, TanL, YuJT (2017) PGRN is associated with late-onset Alzheimer’s disease: A case-control replication study and meta-analysis. Mol Neurobiol54, 1187–1195.
52.
ViswanathanJ, MäkinenP, HelisalmiS, HaapasaloA, SoininenH, HiltunenM (2009) An association study between granulin gene polymorphisms and Alzheimer’s disease in Finnish population. Am J Med Genet B150B, 747–750.
LeeMJ, ChenTF, ChengTW, ChiuMJ (2011) Rs5848 variant of progranulin gene is a risk of Alzheimer’s disease in the Taiwanese population. Dis8, 216–220.
55.
RademakersR, EriksenJL, BakerM, RobinsonT, AhmedZ, LincolnSJ, FinchN, RutherfordNJ, CrookRJ, JosephsKA, BoeveBF, KnopmanDS, PetersenRC, ParisiJE, CaselliRJ, WszolekZK, UittiRJ, FeldmanH, HuttonML, MackenzieIR, Graff-RadfordNR, DicksonDW (2008) Common variation in the Mir-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet17, 3631–3642.
56.
ChangKH, ChenCM, ChenYC, HsiaoYC, HuangCC, KuoHC, HsuHC, Lee-ChenGJ, WuYR (2013) Association between GRN Rs5848 polymorphism and Parkinson’s disease in Taiwanese population. One8, E54448.
57.
TibleOP, RieseF, SavaskanE, Von GuntenA (2017) Best practice in the management of behavioural and psychological symptoms of dementia. Adv Neurol Disord10, 297–309.
58.
Cohen-MansfieldJ (2001) Nonpharmacologic interventions for inappropriate behaviors in dementia: A review, summary, and critique. Am J Geriatr Psychiatry9, 361–381.
59.
BarroRJ, LeeJW (2013) A new data set of educational attainment in the world, 1950–2010. J Dev Econ104, 184–198.
