Digital biomarker-based individualized prognosis for people at risk of dementia.

Background: Research investigating treatments and interventions for cognitive decline fail due to difficulties in accurately recognizing behavioral signatures in the presymptomatic stages of the disease. For this validation study, we took our previously constructed digital biomarker-based prognostic models and focused on generalizability and robustness of the models. Method: We validated prognostic models characterizing subjects using digital biomarkers in a longitudinal, multi-site, 40-month prospective study collecting data in memory clinics, general practitioner offices, and home environments. Results: Our models were able to accurately discriminate between healthy subjects and individuals at risk to progress to dementia within 3 years. The model was also able to differentiate between people with or without amyloid neuropathology and classify fast and slow cognitive decliners with a very good diagnostic performance. Conclusion: Digital biomarker prognostic models can be a useful tool to assist large-scale population screening for the early detection of cognitive impairment and patient monitoring over time.

Subtle visuomotor difficulties in preclinical Alzheimer's disease.

BACKGROUND: Individuals with preclinical Alzheimer's disease (Pre-AD) present nonimpaired cognition, as measured by standard neuropsychological tests. However, detecting subtle difficulties in cognitive functions may be necessary for an early diagnosis and intervention. OBJECTIVES: A new computer-based visuomotor coordination task (VMC) was developed to investigate the possible presence of early visuomotor difficulties in Pre-AD individuals. Associations between VMC task performance and AD biomarkers were studied. The influence of ApoE status on participants' performance was addressed, as well as the relationship between performance and subjective cognitive decline (SCD). METHODS: Sixty-six cognitively normal (CN) elders (19 Pre-AD and 47 control participants [CTR]) and 15 patients with AD performed the VMC task, which consisted in executing visually guided goal-directed movements that required the coordination of the visual and motor systems. All participants underwent ApoE analysis and lumbar puncture. CN participants also completed an extensive standard neuropsychological battery. RESULTS: Despite presenting normal cognition in standard tests, Pre-AD participants exhibited higher response times (RTs) to complete the VMC task than CTR (p < .01). Besides, patients with AD showed higher RTs than CTR (p < .001) and Pre-AD (p < .05), and more errors than CTR (p < .005). RTs in ApoE4 carriers were higher than that observed in ApoE4 noncarriers (p < .01). In CN individuals, RTs were related to amyloid ß-protein 42 (AB42) biomarker (p < .01) and informant-rated SCD (p < .01). CONCLUSIONS: The VMC task is able to discriminate Pre-AD from CTR individuals. Moreover, VMC results are associated with AB42 levels in CN individuals, suggesting that visuomotor dysfunction may be a sensitive marker of Pre-AD.

Informants' Perception of Subjective Cognitive Decline Helps to Discriminate Preclinical Alzheimer's Disease from Normal Aging.

BACKGROUND: Self-reported and informant-reported subjective cognitive decline (SCD) may be useful in the detection of preclinical Alzheimer's disease (Pre-AD) and cognitive impairment related to abnormal amyloid-ß (Aß 42) levels. OBJECTIVES: a) To compare the Subjective Cognitive Decline Questionnaire (SCD-Q) ratings between Pre-AD subjects and cognitively healthy controls, b) to study the association of SCD-Q scores with levels of AD biomarkers in cognitively healthy and cognitively impaired subjects, and c) to compare SCD-Q ratings in cognitively impaired subjects with or without abnormal Aß 42. METHODS: Two hundred and seventeen participants (111 subjects; 106 informants) answered the SCD-Q. All subjects underwent a lumbar puncture to determine levels of Aß 42 and tau, and an extensive neuropsychological battery. Healthy subjects were classified as Controls (CTR) or Pre-AD according to the absence or the presence of abnormal Aß 42, and those with cognitive impairment (CI) into Non-amyloid (NonAB-CI) or Amyloid (AB-CI) impairment. RESULTS: Informants' SCD-Q scores were significantly higher in the Pre-AD group than in the CTR group (F = 6.75; p = 0.01). No significant differences were found in self-ratings. In the cognitively impaired groups, there were no significant differences in the SCD-Q ratings. In the whole sample, informants' ratings of SCD-Q correlated with Aß 42 (r = -0.21; p = 0.02) and tau levels (r = 0.28; p = 0.00). CONCLUSIONS: Higher informants' ratings of SCD-Q differentiated Pre-AD subjects from CTR. Informants' ratings of SCD-Q correlated weakly with cerebrospinal fluid AD biomarkers.