Early detection of subtle motor dysfunction in cognitively normal subjects with amyloid-ß positivity.

Since the current neuropsychological assessments are not sensitive to subtle deficits that may be present in cognitively normal subjects with amyloid-ß positivity, more accurate and efficient measures are needed. Our aim was to investigate the presence of subtle motor deficits in this population and its relationship with cerebrospinal fluid (CSF) amyloid-ß levels. We adapted the Finger Tapping Task to measure tapping speed and intrasubject variability. Seventy-two right-handed participants completed the study. Subjects were divided into three groups according to their CSF biomarker profile: 37 control participants (negative CSF AD biomarkers, CTR), 20 cognitively normal subjects with amyloid-ß positivity (abnormal levels of CSF Aß42, Aß+) and 15 AD patients. All subjects underwent lumbar puncture for the CSF analysis, apolipoprotein E genotyping and completed the Finger Tapping Task, a neuropsychological battery and cardiovascular risk factor and physical activity assessments. An overall difference between groups was found both in tapping speed [F(2,66) = 19.37, p < .01] and in intrasubject variability [F(2,66) = 11.40, p < .01]. More specifically, the Aß+ group showed lower speed [F(1,52) = 5.33, p < .05] and greater intrasubject variability [F(1,52) = 8.48, p < .01] than the CTR group, and higher speed than the AD group [F(1,30) = 13.61, p < .01]. Speed (ß = .263, p < .05) and intrasubject variability (ß = -.558, p < .01) were significantly associated with CSF amyloid-ß levels. The present findings suggest that subtle motor difficulties can be detected in cognitively healthy subjects with amyloid-ß positivity and be related to CSF Aß42 levels. An accurate assessment of motor functions could help on identifying individuals at the earliest stage of the Alzheimer's continuum.

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.

The Subjective Cognitive Decline Questionnaire (SCD-Q): a validation study.

BACKGROUND: Subjective cognitive decline (SCD) is gaining importance as a focus of investigation, but adequate tools are needed for its quantification. OBJECTIVE: To develop and validate a questionnaire to quantify SCD, termed the Subjective Cognitive Decline Questionnaire (SCD-Q). METHODS: 124 controls (CTR), 144 individuals with SCD, 83 mild cognitive impairment subjects, 46 Alzheimer's disease patients, and 397 informants were included. The SCD-Q contains: part I, named MyCog, which is answered by the subject; and part II, TheirCog, which includes the same questions and is answered by the informant or caregiver. The 24 SCD-Q items assess the perceived subjective decline in memory, language, and executive functions in the last two years. RESULTS: The MyCog scores of controls differed significantly from those of the other groups (p < 0.05) and there were significant differences in TheirCog scores between all groups. The optimal TheirCog cut-off score for discriminating between individuals with and without cognitive impairment was 7/24 (sensitivity 85%, specificity 80%). MyCog scores correlated significantly with anxiety and depression (r = 0.29, r = 0.43, p < 0.005), but no correlations were found with neuropsychological tests. TheirCog scores correlated significantly with most of the neuropsychological tests (p < 0.05). Informants' depression and anxiety influenced TheirCog scores in controls and SCD groups. CONCLUSION: Self-perceived cognitive decline, measured by the SCD-Q part I (MyCog), discriminated SCD from CTR. Part II (TheirCog) was strongly related to subjects' objective cognitive performance, and discriminated between subjects with or without cognitive impairment. The SCD-Q is a useful tool to measure self-perceived cognitive decline incorporating the decliner and the informant perspective.