Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y et al. Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol 8: 619-627

Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, University of Maastricht, 6200 MD Maastricht, Netherlands.
The Lancet Neurology (Impact Factor: 21.9). 08/2009; 8(7):619-27. DOI: 10.1016/S1474-4422(09)70139-5
Source: PubMed


Alzheimer's disease (AD) pathology is common in patients with amnestic mild cognitive impairment (aMCI) without dementia, but the prevalence of AD pathology in patients with subjective cognitive impairment (SCI) and non-amnestic mild cognitive impairment (naMCI) is unknown. AD is characterised by decreased CSF concentrations of Abeta(42) and increased concentrations of tau. We investigated the prevalence of a CSF AD profile in patients with SCI, naMCI, or aMCI and the association of this profile with cognitive outcome in each group.
Patients with SCI, naMCI, aMCI, and neurologically healthy controls were recruited from 20 memory clinics across Europe, between January, 2003, and June, 2005, into this prospective cohort study. A CSF AD profile was defined as an abnormal ratio of Abeta(42):tau. Patients were assessed annually up to 3 years. Outcome measures were changes in memory, overall cognition, mini-mental state examination (MMSE) score, daily function, and progression to AD-type dementia.
The CSF AD profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]) than in healthy controls (28 of 89 [31%]). The profile was associated with cognitive decline in patients with naMCI (memory, MMSE, and daily function) and in patients with aMCI (MMSE and daily function). In patients with aMCI, a CSF AD profile was predictive of AD-type dementia (OR 26.8, 95% CI 1.6-456.4).
AD is a common cause of SCI, naMCI, and aMCI and is associated with cognitive decline in patients with naMCI or aMCI. Patients with SCI might be in the early stages of AD, and cognitive decline might become apparent only after longer follow-up.
European Commission; Ana Aslan International Foundation.

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    • "However, there are some controversial findings on the role of SMI in AD. While some crosssectional studies support SMI as strongly related to affective symptoms [3] [4] [5] [6] [7] [8], others have demonstrated that higher SMI are associated with AD biomarkers, such as greater amyloid-(A) deposition [9] [10], decreased metabolism in 2-[18F] fluoro-2-deoxy-D- glucose positron emission tomography (FDG-PET) [11], atrophy on magnetic resonance imaging ADrelated brain regions [12] [13] [14], and cerebrospinal fluid AD profile [11] [15]. "
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    ABSTRACT: Background: Subjective memory impairment (SMI) refers to subjective awareness of initial memory decline undetectable with existing standardized cognitive tests. The Face Name Associative Memory Exam (FNAME) was created to detect memory deficits in individuals with preclinical Alzheimer's disease (AD). We reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively normal (CN) Spanish-speaking subjects >49. Objective: To determine whether higher SMI [a modification of Memory Failures Everyday (MFE-30)] was related to worse memory performance (S-FNAME) or associated with greater affective symptoms in subjects >49; and whether MFE-30 and FNAME were able to discriminate between CN and mild cognitive impairment (MCI) subjects. Methods: 317 subjects (CN = 196, MCI = 121) were included in the analysis because they attended the annual "Open House Initiative" at Memory Clinic Fundació ACE, were >49 years, literate, received S-FNAME, MFE-30, and Hospital Anxiety and Depression Scale, had Mini-Mental State Exam scores ≥27, and returned to complete a comprehensive diagnostic assessment. Results: MFE-30 scores were associated with affective symptoms but not with S-FNAME performance. S-FNAME scores were related to performance on memory variables of NBACE (neuropsychological battery used in Fundació ACE). Although the MCI group showed significantly higher MFE-30 and worse S-FNAME scores than the CN group, their discriminability values were similar (Sensitivity: 49.6 versus 52.9; Specificity: 85.1 versus 83.6, respectively). Conclusions: SMI was more related to depressive symptoms than to S-FNAME memory performance; and S-FNAME scores were related to other episodic memory test performances, but neither to affective symptoms nor to SMI. MFE-30 and S-FNAME are not optimal for discriminating between CN and MCI groups. Longitudinal follow-up will determine if lower S-FNAME and higher SMI are related to increased risk of AD.
    Journal of Alzheimer's disease: JAD 10/2015; 48(4). DOI:10.3233/JAD-150594 · 4.15 Impact Factor
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    • "Recent more comprehensive studies of cognitively normal elderly [11] indicate that subjective cognitive decline (SCD) may be associated with subtle ADlike features on MRI [12], altered AD biomarkers in cerebrospinal fluid (CSF) [13], and increased risk of progression to MCI and AD [11]. Still SCD is an unspecific phenomenon which may be associated with a range of medical, neurologic, and psychiatric conditions and additional exclusion and inclusion criteria are needed to identify a sub-group at risk for dementia. "
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    ABSTRACT: Background: There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. Objective: The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. Methods: 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. Results: The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. Conclusions: The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.
    Journal of Alzheimer's disease: JAD 09/2015; 47(3):619-628. DOI:10.3233/JAD-150109 · 4.15 Impact Factor
    • "Subjective cognitive decline (SCD) in older adults is increasingly recognized as a potential indicator of non-normative cognitive decline and eventual progression to dementia [1] [2] [3] [4] [5]. Moreover, there is emerging evidence of associations of SCD with Alzheimer's disease (AD) biomarkers and neuroimaging markers [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16], such as gray matter volume loss [6] [7] [8], cerebral hypometabolism [10], and amyloid deposition [12] [13] [14], in the absence of objective cognitive dysfunction or depression. Given research supporting SCD as a risk factor for AD in some individuals, the National Institute on Aging–Alzheimer's Association preclinical AD working group has included SCD as a feature, highlighting its importance in disease detection and prevention [17]. "
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    ABSTRACT: Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.
    Journal of Alzheimer's disease: JAD 09/2015; 48(s1). DOI:10.3233/JAD-150154 · 4.15 Impact Factor
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