title: Diagnostic differentiation of mild cognitive impairment due to Alzheimer's disease using a hippocampus-dependent test of spatial memory.
abstract: The hippocampus is one of the earliest brain regions affected in Alzheimer's disease (AD) and tests of hippocampal function have the potential to detect AD in its earliest stages. Given that the hippocampus is critically involved in allocentric spatial memory, this study applied a short test of spatial memory, the 4 Mountains Test (4MT), to determine whether test performance can differentiate mild cognitive impairment (MCI) patients with and without CSF biomarker evidence of underlying AD and whether the test can distinguish patients with MCI and mild AD dementia when applied in different cultural settings. Healthy controls (HC), patients with MCI, and mild AD dementia were recruited from study sites in UK and Italy. Study numbers were: HC (UK 20, Italy 10), MCI (UK 21, Italy 14), and AD (UK 11, Italy 9). Nineteen UK MCI patients were grouped into CSF biomarker-positive (MCI+, n = 10) and biomarker-negative (MCI-, n = 9) subgroups. Behavioral data were correlated with hippocampal volume and cortical thickness of the precuneus and posterior cingulate gyrus. Spatial memory was impaired in both UK and Italy MCI and AD patients. Test performance additionally differentiated between MCI+ and MCI- subgroups (P = 0.001). A 4MT score of ≤8/15 was associated with 100% sensitivity and 90% specificity for detection of early AD (MCI+ and mild AD dementia) in the UK population, and with 100% sensitivity and 50% specificity for detection of MCI and AD in the Italy sample. 4MT performance correlated with hippocampal volume in the UK population and cortical thickness of the precuneus in both study populations. In conclusion, performance on a hippocampus-sensitive test of spatial memory differentiates MCI due to AD with high diagnostic sensitivity and specificity. The observation that similar diagnostic sensitivity was obtained in two separate study populations, allied to the scalability and usability of the test in community memory clinics, supports future application of the 4MT in the diagnosis of pre-dementia due to AD.
authors.affiliation: Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Kuven
authors.initials: K
authors.lastname: Moodley
authors.affiliation: Brighton and Sussex Medical School, Brighton, United Kingdom.|U.O. Direzione Scientifica, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: Minati
authors.affiliation: U.O Neuroradiologia, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Contarino
authors.affiliation: U.O. Neuropatologia, Fondazione IRCCS Istituto Neurologico"Carlo Besta", Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Prioni
authors.affiliation: Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Wood
authors.affiliation: Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cooper
authors.affiliation: U.O Neuroradiologia, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: D'Incerti
authors.affiliation: U.O. Neuropatologia, Fondazione IRCCS Istituto Neurologico"Carlo Besta", Milano, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Dennis
authors.initials: D
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology; D000704:Analysis of Variance; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D013028:Space Perception / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology*; D013223:Statistics as Topic; D006113:United Kingdom
keywords: Alzheimer's disease; hippocampus; mild cognitive impairment; precuneus; spatial memory