Sex effects on the progression of Alzheimer’s disease (AD) have received less attention than other demographic factors, including onset age and education.
Objective:
The aim of this study was to investigate whether sex affected cortical thinning in the disease progression of AD.
Methods:
We prospectively recruited 36 patients with early-stage AD and 14 people with normal cognition. All subjects were assessed with magnetic resonance imaging at baseline, Year 1, Year 3, and Year 5. We performed cortical thickness analyses using surface-based morphometry on magnetic resonance imaging.
Results:
Women with AD showed more rapid cortical thinning in the left dorsolateral frontal cortex, left superior temporal gyrus, bilateral temporo-parietal association cortices, bilateral anterior cingulate gyri, bilateral medial frontal cortices, and bilateral occipital cortices over 5 years than men with AD, even though there was no difference in cortical thickness at baseline. In contrast, there were no regions of significantly more rapid atrophy in men with AD.
Conclusions:
Our findings suggest that women deteriorate faster than men in the progression of AD.
WeuveJ, HebertLE, ScherrPA, EvansDA (2015) Prevalence of Alzheimer disease in US states. Epidemiology26, e4-6.
2.
GaoS, HendrieHC, HallKS, HuiS (1998) The relationships between age, sex, and the incidence of dementia and Alzheimer disease: A meta-analysis. Arch Gen Psychiatry55, 809-815.
HaywoodWM, Mukaetova-LadinskaEB (2006) Sex influences on cholinesterase inhibitor treatment in elderly individuals with Alzheimer’s disease. Am J Geriatr Pharmacother4, 273-286.
5.
KimS, KimMJ, KimS, KangHS, LimSW, MyungW, LeeY, HongCH, ChoiSH, NaDL, SeoSW, KuBD, KimSY, KimSY, JeongJH, ParkSA, CarrollBJ, KimDK (2015) Gender differences in risk factors for transition from mild cognitive impairment to Alzheimer’s disease: A CREDOS study. Compr Psychiatry62, 114-122.
6.
ScacchiR, GambinaG, BroggioE, CorboRM (2014) Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer’s disease. Int J Geriatr Psychiatry29, 610-615.
7.
WattmoC, WallinAK, LondosE, MinthonL (2011) Predictors of long-term cognitive outcome in Alzheimer’s disease. Alzheimers Res Ther3, 23.
8.
GieddJN, RaznahanA, MillsKL, LenrootRK (2012) Review: Magnetic resonance imaging of male/female differences in human adolescent brain anatomy. Biol Sex Differ3, 19.
9.
AndreanoJM, CahillL (2009) Sex influences on the neurobiology of learning and memory. Learn Mem16, 248-266.
10.
SundermannEE, BiegonA, RubinLH, LiptonRB, MowreyW, LandauS, MakiPM, Alzheimer’sDisease Neuroimaging Initiative (2016) Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy. Neurology86, 1368-1376.
SunY, LeeR, ChenY, CollinsonS, ThakorN, BezerianosA, SimK (2015) Progressive gender differences of structural brain networks in healthy adults: A longitudinal, diffusion tensor imaging study. PLoS One10, e0118857.
13.
BallmaierM, O’BrienJT, BurtonEJ, ThompsonPM, RexDE, NarrKL, McKeithIG, DeLucaH, TogaAW (2004) Comparing gray matter loss profiles between dementia with Lewy bodies and Alzheimer’s disease using cortical pattern matching: Diagnosis and gender effects. Neuroimage23, 325-335.
14.
CallenDJ, BlackSE, CaldwellCB, GradyCL (2004) The influence of sex on limbic volume and perfusion in AD. Neurobiol Aging25, 761-770.
15.
KidronD, BlackSE, StanchevP, BuckB, SzalaiJP, ParkerJ, SzekelyC, BronskillMJ (1997) Quantitative MR volumetry in Alzheimer’s disease. Topographic markers and the effects of sex and education. Neurology49, 1504-1512.
16.
ApostolovaLG, DinovID, DuttonRA, HayashiKM, TogaAW, CummingsJL, ThompsonPM (2006) 3D comon of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer’s disease. Brain129, 2867-2873.
17.
CarmichaelOT, KullerLH, LopezOL, ThompsonPM, DuttonRA, LuA, LeeSE, LeeJY, AizensteinHJ, MeltzerCC, LiuY, TogaAW, BeckerJT (2007) Ventricular volume and dementia progression in the Cardiovascular Health Study. Neurobiol Aging28, 389-397.
18.
SmithCD, PettigrewLC, AvisonMJ, KirschJE, TinkhtmanAJ, SchmittFA, WermelingDP, WeksteinDR, MarkesberryWR (1995) Frontal lobe phosphorus metabolism and neuropsychological function in aging and in Alzheimer’s disease. Ann Neurol38, 194-201.
19.
EdlandSD, XuY, PlevakM, O’BrienP, TangalosEG, PetersenRC, JackCRJr (2002) Total intracranial volume: Normative values and lack of association with Alzheimer’s disease. Neurology59, 272-274.
20.
SalatDH, KayeJA, JanowskyJS (1999) Prefrontal gray and white matter volumes in healthy aging and Alzheimer disease. Arch Neurol56, 338-344.
21.
HuaX, HibarDP, LeeS, TogaAW, JackCRJr, WeinerMW, ThompsonPM, Alzheimer’sDisease Neuroimaging Initiative (2010) Sex and age differences in atrophic rates: An ADNI study with n=1368 MRI scans. Neurobiol Aging31, 1463-1480.
22.
JulkunenV, NiskanenE, KoikkalainenJ, HerukkaSK, PihlajamakiM, HallikainenM, KivipeltoM, MuehlboeckS, EvansAC, VanninenR, HilkkaS (2010) Differences in cortical thickness in healthy controls, subjects with mild cognitive impairment, and Alzheimer’s disease patients: A longitudinal study. J Alzheimers Dis21, 1141-1151.
23.
ChoH, JeonS, KangSJ, LeeJM, LeeJH, KimGH, ShinJS, KimCH, NohY, ImK, KimST, ChinJ, SeoSW, NaDL (2013) Longitudinal changes of cortical thickness in early- versus late-onset Alzheimer’s disease. Neurobiol Aging34, 1921e1929-1921e1915.
ChoH, SeoSW, KimJH, KimC, YeBS, KimGH, NohY, KimHJ, YoonCW, SeongJK, KimCH, KangSJ, ChinJ, KimST, LeeKH, NaDL (2013) Changes in subcortical structures in early- versus late-onset Alzheimer’s disease. Neurobiol Aging34, 1740-1747.
26.
American Psychiatric Association (1994), Diagnostic criteria from DSM-IV. Washington, DC.
27.
McKhannG, DrachmanD, FolsteinM, KatzmanR, PriceD, StadlanEM (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology34, 939-944.
28.
SeoSW, ImK, LeeJM, KimST, AhnHJ, GoSM, KimSH, NaDL (2011) Effects of demographic factors on cortical thickness in Alzheimer’s disease. Neurobiol Aging32, 200-209.
29.
BenjaminiY, DraiD, ElmerG, KafkafiN, GolaniI (2001) Controlling the false discovery rate in behor genetics research. Behav Brain Res125, 279-284.
30.
BarnesLL, WilsonRS, BieniasJL, SchneiderJA, EvansDA, BennettDA (2005) Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch Gen Psychiatry62, 685-691.
31.
SundermannEE, BiegonA, RubinLH, LiptonRB, LandauS, MakiPM, Alzheimer’sDisease Neuroimaging Initiative (2017) Does the female advantage in verbal memory contribute to underestimating Alzheimer’s disease pathology in women versus men?. J Alzheimers Dis56, 947-957.
32.
BorrasC, GambiniJ, Gomez-CabreraMC, SastreJ, PallardoFV, MannGE, VinaJ (2005) 17beta-oestradiol up-regulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2[MAPK]/NFkappaB cascade. Aging Cell4, 113-118.
33.
VinaJ, LloretA, VallesSL, BorrasC, BadiaMC, PallardoFV, SastreJ, AlonsoMD (2007) Effect of gender on mitochondrial toxicity of Alzheimer’s Abeta peptide. Antioxid Redox Signal9, 1677-1690.
VinaJ, LloretA (2010) Why women have more Alzheimer’s disease than men: Gender and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis20(Suppl 2), S527-533.
36.
LiY, WangY, WuG, ShiF, ZhouL, LinW, ShenD, Alzheimer’sDisease Neuroimaging Initiative (2012) Discriminant analysis of longitudinal cortical thickness changes in Alzheimer’s disease using dynamic and network features. Neurobiol Aging33, 427. e415-430.
37.
DickersonBC, BakkourA, SalatDH, FeczkoE, PachecoJ, GreveDN, GrodsteinF, WrightCI, BlackerD, RosasHD, SperlingRA, AtriA, GrowdonJH, HymanBT, MorrisJC, FischlB, BucknerRL (2009) The cortical signature of Alzheimer’s disease: Regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex19, 497-510.
38.
AhnHJ, SeoSW, ChinJ, SuhMK, LeeBH, KimST, ImK, LeeJM, LeeJH, HeilmanKM, NaDL (2011) The cortical neuroanatomy of neuropsychological deficits in mild cognitive impairment and Alzheimer’s disease: A surface-based morphometric analysis. Neuropsychologia49, 3931-3945.
39.
SabuncuMR, DesikanRS, SepulcreJ, YeoBT, LiuH, SchmanskyNJ, ReuterM, WeinerMW, BucknerRL, SperlingRA, FischlB, Alzheimer’sDisease Neuroimaging Initiative (2011) The dynamics of cortical and hippocampal atrophy in Alzheimer disease. Arch Neurol68, 1040-1048.
