The differentiation of Alzheimer’s disease (AD) from age-related limbic tauopathies (LT), including argyrophilic grain disease (AGD) and senile dementia of the neurofibrillary tangle type (SD-NFT), is often challenging because specific clinical diagnostic criteria have not yet been established. Despite the utility of specific biomarkers evaluating amyloid and tau to detect the AD-related pathophysiological changes, the expense and associated invasiveness preclude their use as first-line diagnostic tools for all demented patients. Therefore, less invasive and costly biomarkers would be valuable in routine clinical practice for the differentiation of AD and LT.
Objective:
The purpose of this study is to develop a simple reproducible method on magnetic resonance imaging (MRI) that could be adopted in daily clinical practice for the differentiation of AD and other forms of LT.
Methods:
Our newly proposed three quantitative indices and well-known medial temporal atrophy (MTA) score were evaluated using MRI of pathologically-proven advanced-stage 21 AD, 10 AGD, and 2 SD-NFT patients.
Results:
Contrary to MTA score, hippocampal angle (HPA), inferior horn area (IHA), and ratio between HPA and IHA (i.e., IHPA index) demonstrated higher diagnostic performance and reproducibility, especially to differentiate advanced-stage AD patients with Braak neurofibrillary tangle stage V/VI from LT patients (the area under the receiver-operating-characteristic curve of 0.83, 089, and 0.91; intraclass correlation coefficients of 0.930, 0.998, and 0.995, respectively).
Conclusion:
Quantitative indices reflecting hippocampal deformation with ventricular enlargement are useful to differentiate advanced-stage AD from LT. This simple and convenient method could be useful in daily clinical practice.
O’BrienJT, HolmesC, JonesM, JonesR, LivingstonG, McKeithI, MittlerP, PassmoreP, RitchieC, RobinsonL, SampsonEL, TaylorJP, ThomasA, BurnsA (2017) Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol31, 147–168.
YamadaM (2003) Senile dementia of the neurofibrillary tangle type (tangle-only dementia): Neuropathological criteria and clinical guidelines for diagnosis. Neuropathology23, 311–317.
4.
YamadaM, ItohY, OtomoE, SuematsuN, MatsushitaM (1996) Dementia of the Alzheimer type and related dementias in the aged: DAT subgroups and senile dementia of the neurofibrillary tangle type. Neuropathology16, 89–98.
JellingerKA, BancherC (1998) Senile dementia with tangles (tangle predominant form of senile dementia). Brain Pathol8, 367–376.
7.
TolnayM, ClavagueraF (2004) Argyrophilic grain disease: A late-onset dementia with distinctive features among tauopathies. Neuropathology24, 269–283.
8.
RodriguezRD, SuemotoCK, MolinaM, NascimentoCF, LeiteRE, de Lucena Ferretti-RebustiniRE, FarfelJM, HeinsenH, NitriniR, UedaK, PasqualucciCA, Jacob-FilhoW, YaffeK, GrinbergLT (2016) Argyrophilic grain disease: Demographics, clinical, and neuropathological features from a large autopsy study. J Neuropathol Exp Neurol75, 628–635.
9.
Esteban de AntonioE, López-ÁlvarezJ, RábanoA, Agüera-OrtizL, Sánchez-SoblecheroA, AmayaL, PortelaS, CátedraC, OlazaránJ (2020) Pathological correlations of neuropsychiatric symptoms in institutionalized people with dementia. J Alzheimers Dis78, 1731–1741.
10.
BarkhofF, PolvikoskiTM, van StraatenEC, KalariaRN, SulkavaR, AronenHJ, NiinistöL, RastasS, OinasM, ScheltensP, ErkinjunttiT (2007) The significance of medial temporal lobe atrophy: A postmortem MRI study in the very old. Neurology69, 1521–1527.
11.
SakuraiK, TokumaruAM, IkedaT, MorimotoS, InuiS, SumidaK, ObaH, NakagawaM, MatsukawaN, HashizumeY (2019) Characteristic asymmetric limbic and anterior temporal atrophy in demented patients with pathologically confirmed argyrophilic grain disease. Neuroradiology61, 1239–1249.
HarperL, BouwmanF, BurtonEJ, BarkhofF, ScheltensP, O’BrienJT, FoxNC, RidgwayGR, SchottJM (2017) Patterns of atrophy in pathologically confirmed dementias: A voxelwise analysis. J Neurol Neurosurg Psychiatry88, 908–916.
14.
RamusinoMC, GaribottoV, BacchinR, AltomareD, DodichA, AssalF, MendesA, CostaA, TinazziM, MorbelliSD, BaucknehtM, PiccoA, DottoriniME, TranfagliaC, FarottiL, SalvadoriN, MorettiD, SavelliG, TaralloA, NobiliF, ParapiniM, CavaliereC, SalvatoreE, SalvatoreM, BoccardiM, FrisoniGB (2020) Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer’s disease. Eur J Nucl Med Mol Imaging47, 270–280.
15.
SchroeterML, TiepoltS, MarschhauserA, Thöne-OttoA, HoffmannKT, BarthelH, ObrigH, SabriO (2015) Dissociation of amyloid biomarkers in PET and CSF in Alzheimer’s disease: A case report. BMC Neurol15, 152.
16.
MontineTJ, PhelpsCH, BeachTG, BigioEH, CairnsNJ, DicksonDW, DuyckaertsC, FroschMP, MasliahE, MirraSS, NelsonPT, SchneiderJA, ThalDR, TrojanowskiJQ, VintersHV, HymanBT (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: A practical approach. Acta Neuropathol123, 1–11.
ScheltensP, LeysD, BarkhofF, HugloD, WeinsteinHC, VermerschP, KuiperM, SteinlingM, WoltersEC, ValkJ (1992) Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: Diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry55, 967–972.
24.
MirraSS, HeymanA, McKeelD, SumiSM, CrainBJ, BrownleeLM, VogelFS, HughesJP, van BelleG, BergL (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology41, 479–486.
25.
DingZT, WangY, JiangYP, YoshidaM, MimuroM, InagakiT, IwaseT, HashizumeY (2006) Argyrophilic grain disease: Frequency and neuropathology in centenarians. Acta Neuropathol111, 320–328.
26.
MatsuiY, TanizakiY, ArimaH, YonemotoK, DoiY, NinomiyaT, SasakiK, IidaM, IwakiT, KanbaS, KiyoharaY, (2009) Incidence and survival of dementia in a general population of Japanese elderly: The Hisayama study. J Neurol Neurosurg Psychiatry80, 366–370.
27.
BraakH, BraakE (1987) Argyrophilic grains: Characteristic pathology of cerebral cortex in cases of adult onset dementia without Alzheimer changes. Neurosci Lett76, 124–127.
JosephsKA, MurrayME, TosakulwongN, WhitwellJL, KnopmanDS, MachuldaMM, WeigandSD, BoeveBF, KantarciK, PetrucelliL, LoweVJ, JackCRJr., PetersenRC, ParisiJE, DicksonDW (2017) Tau aggregation influences cognition and hippocampal atrophy in the absence of beta-amyloid: A clinico-imaging-pathological study of primary age-related tauopathy (PART). Acta Neuropathol133, 705–715.
NestorSM, RupsinghR, BorrieM, SmithM, AccomazziV, WellsJL, FogartyJ, BarthaR (2008) Ventricular enlargement as a possible measure of Alzheimer’s disease progression validated using the Alzheimer’s Disease Neuroimaging Initiative database. Brain131, 2443–2454.
36.
JackCRJr., ShiungMM, GunterJL, O’BrienPC, WeigandSD, KnopmanDS, BoeveBF, IvnikRJ, SmithGE, ChaRH, TangalosEG, PetersenRC (2004) Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology62, 591–600.
37.
HayashiT, WadaA, UchidaN, KitagakiH (2009) Enlargement of the hippocampal angle: A new index of Alzheimer disease. Magn Reson Med Sci8, 33–38.
