Path Integration Detects Prodromal Alzheimer's Disease and Predicts Cognitive Decline.

Background: The entorhinal cortex is the very earliest involvement of Alzheimer's disease (AD). Grid cells in the medial entorhinal cortex form part of the spatial navigation system. Objective: We aimed to determine whether path integration performance can be used to detect patients with mild cognitive impairment (MCI) at high risk of developing AD, and whether it can predict cognitive decline. Methods: Path integration performance was assessed in 71 patients with early MCI (EMCI) and late MCI (LMCI) using a recently developed 3D virtual reality navigation task. Patients with LMCI were further divided into those displaying characteristic brain imaging features of AD, including medial temporal lobe atrophy on magnetic resonance imaging and posterior hypoperfusion on single-photon emission tomography (LMCI+), and those not displaying such features (LMCI-). Results: Path integration performance was significantly lower in patients with LMCI+than in those with EMCI and LMCI-. A significantly lower performance was observed in patients who showed progression of MCI during 12 months, than in those with stable MCI. Path integration performance distinguished patients with progressive MCI from those with stable MCI, with a high classification accuracy (a sensitivity of 0.88 and a specificity of 0.70). Conclusions: Our results suggest that the 3D virtual reality navigation task detects prodromal AD patients and predicts cognitive decline after 12 months. Our navigation task, which is simple, short (12-15 minutes), noninvasive, and inexpensive, may be a screening tool for therapeutic choice of disease-modifiers in individuals with prodromal AD.

Factors and brain imaging features associated with cognition in oldest-old patients with Alzheimer-type dementia.

BACKGROUND: The underlying pathophysiology of cognitive dysfunction in oldest-old patients with Alzheimer-type dementia (AD) has not been clarified to date. We aimed to determine the factors and brain imaging features associated with cognition in oldest-old patients with AD. METHODS: We enrolled 456 consecutive outpatients with probable AD (145 men and 311 women, age range: 51-95 years). Demographic factors, such as education level, disease duration at initial visit, body mass index, comorbidities, frailty, and leisure activity, and brain imaging features, including severity of medial temporal lobe (MTL) atrophy, white matter lesions and infarcts, and frequency of posterior cerebral hypoperfusion were compared among pre-old (≤ 74 years), old (75 to 84 years), and oldest-old (≥ 85 years) subgroups. RESULTS: The oldest-old subgroup showed significantly longer disease duration, lower education level, more severe frailty, less leisure activity, worse cognitive impairment, a tendency of slower progression of cognitive decline, greater MTL atrophy, more severe white matter hyperintensities and infarcts, and lower frequency of posterior hypoperfusion than the younger age subgroups. Regarding the brain imaging subtypes, there were significantly more patients with the limbic-predominant subtype and fewer patients with the hippocampal-sparing subtype in the oldest-old AD group than the pre-old AD group. CONCLUSIONS: Oldest-old patients with AD show different factors and brain imaging features associated with cognition from pre-old and old patients. Our results are expected to provide useful information towards understanding the pathophysiology of oldest-old patients with AD, and for determining their clinical diagnosis and appropriate management methods.