Determinants, MRI Correlates, and Prognosis of Mild Cognitive Impairment: The Rotterdam Study

Abstract

Mild cognitive impairment (MCI) marks a transitional stage between healthy aging and dementia, but the understanding of MCI in the general population remains limited. We investigated determinants, MRI-correlates, and prognosis of MCI within the population-based Rotterdam Study. Firstly, we studied age, APOE-ε4 carriership, waist circumference, hypertension, diabetes mellitus, total and HDL-cholesterol levels, smoking, and stroke as potential determinants of MCI. Determinants were assessed cross-sectionally at baseline (2002-2005) and up to 7 years prior to baseline (1997-2001). Secondly, we compared volumetric, microstructural, and focal MRI-correlates in persons with and without MCI. Thirdly, we followed participants for incident dementia and mortality until 2012. Out of 4,198 participants, 417 had MCI, of whom 163 amnestic and 254 non-amnestic MCI. At baseline, older age, APOE-ε4 carriership, lower total cholesterol levels, and stroke were associated with MCI. Additionally, lower HDL-cholesterol levels and smoking were related to MCI when assessed 7 years prior to baseline. Persons with MCI, particularly those with non-amnestic MCI, had larger white matter lesion volumes, worse microstructural integrity of normal-appearing white matter, and a higher prevalence of lacunes, compared to cognitively healthy participants. MCI was associated with an increased risk of dementia (hazard ratio (HR) 3.98, 95% confidence interval (CI) 2.97;5.33), Alzheimer's disease (HR 4.03, 95% CI 2.92;5.56), and mortality (HR 1.54, 95% CI 1.28;1.85). In conclusion, we found that several vascular risk factors and MRI-correlates of cerebrovascular disease were related to MCI in the general population. Participants with MCI had an increased risk of dementia, including Alzheimer's disease, and mortality.

Apolipoprotein E e4 and Cognitive Function: A Modifiable Association? Results from Two Independent Cohort Studies

“…In agreement with our findings, a very recent analysis also found that APOE e4 was associated with mild cognitive impairment in the general population [22], and a review of in vivo studies showed that APOE e4 was associated with non-pathological changes in brain physiology, which might predispose to neurodegenerative processes [23], possibly including reduced cognitive performance.…”

Detection of mild cognitive impairment in a community‐dwelling population using quantitative, multiparametric MRI‐based classification

“…Classification performance rates of the MCI‐model did not improve over those of the AD‐model or mild‐AD‐model. The incorporation of additional prior, biological knowledge (Rathore et al, ), or other information derived from imaging‐ and nonimaging biomarkers such as cerebrovascular status (De Bruijn et al, ), the load (De Bruijn et al, ; Dong et al, ; Fan et al, ), or location of white matter hyperintensities (McAleese et al, ), cerebral blood flow (Bron et al, ), resting‐state functional MRI (de Vos et al, ; Schouten et al, ), PET‐derived biomarkers (Dukart et al, ; Li et al, ), or additional cognitive assessment scores including measures of cognitive reserve (Allegri et al, ; Moradi et al, ; Vieira, Pinaya, & Mechelli, ; Wang et al, ) may further augment classification accuracy without increasing diagnostic complexity. While cognitive assessment scores would most likely provide a valuable contribution to the detection of MCI (Moradi et al, ; Wang et al, ), we did not consider these for this study.…”

“…Study details can be found elsewhere (Ikram et al, ; Ikram et al, ). For the present analysis we selected 682 subjects that were older than 60 years of age, underwent MRI in the period 2002–2005, did not have MRI‐defined cortical infarcts, and had data available for MCI diagnosis (De Bruijn et al, ). Subjects were diagnosed as MCI according to criteria previously derived for the Rotterdam study (Adams et al, ; De Bruijn et al, ).…”

Mild Cognitive Impairment and Dementia Show Contrasting Associations with Risk of Cancer

“…First, we found stronger effects for amnestic MCI than non-amnestic MCI. Indeed, amnestic MCI is more closely linked to AD pathology than non-amnestic MCI [15]. Second, censoring for dementia did not materially change the risk of cancer after MCI – if anything, the risk slightly attenuated.…”

“…MCI was defined as the presence of self-perceived cognitive complaints (defined as at least one of 6 questions on memory and daily functioning) and cognitive impairment as assessed with neuropsychological tests in the absence of dementia, in persons aged ≥60 years [15]. The neuropsychological tests measured memory function (15-word learning test immediate and delayed), information-­processing speed (LDST, Stroop first and second subtask), and executive functioning (LDST, Stroop third subtask, and WFT).…”