Neuropsychiatric symptoms in older people with and without cognitive impairment

Neuropsychiatric symptoms (NPS) are non-cognitive disturbances such as depression. Rates of NPS have been shown to increase as cognitive ability declines and may be useful in predicting transition from mild cognitive impairment (MCI) to dementia. This community-based study reports the association between NPS and cognitive decline over two years. Participants included 873 community dwelling adults aged 70-90 years enrolled in the Sydney Memory and Ageing Study. NPS were assessed by the Neuropsychiatric Inventory (NPI). Cognitive impairment was defined by diagnosis (MCI or incident dementia) or neuropsychological test performance across five cognitive domains. Cognitive decline was defined by progression to dementia or worse neuropsychological performance. Total NPS at baseline did not differ between those without cognitive impairment (26.2%) and those with MCI (28.8%), but agitation and apathy were associated with MCI. Only baseline depression was associated with dementia at follow-up. Total NPS at baseline was cross-sectionally associated with cognitive impairment in executive function, attention, and global cognition, but did not predict cognitive decline. Depression, anxiety, agitation, anxiety, and apathy were all associated with impairment in at least one cognitive domain, but only anxiety and agitation were significantly associated with cognitive decline. Sensitivity analyses applied more stringent criteria for NPS and cognitive impairment in MCI but did not alter interpretation of results from the main analysis. Overall rates of NPS at baseline were not associated with MCI, dementia, or cognitive decline over two years. Additional follow-up is needed to further examine this association over a longer time course.     

Annual rate and predictors of conversion to dementia in subjects presenting mild cognitive impairment criteria defined according to a population-based study

Elderly subjects diagnosed with mild cognitive impairment (MCI) are becoming the target of intervention trials. The criteria used for MCI are principally issued from prospective clinical studies, although longitudinal population-based studies having identified several cognitive predictors of dementia can be of great contribution in the definition of these criteria. This study was conducted to explore the external validity of MCI criteria issued from a longitudinal population-based study, and subsequently to identify the best predictors of the short-term conversion to Alzheimer's disease 2 years after the MCI diagnosis. Ninety elderly volunteers with memory complaint diagnosed with MCI on the basis of their functional and neuropsychological performances were followed up within 2 years. The potential predictors of the conversion to dementia collected at baseline included age, gender, educational level, size of temporal lobe, apolipoprotein E genotype and a series of neuropsychological measures (Mac Nair Scale, Mini-Mental State Examination, Benton Visual Retention Test, Isaacs Set Test, Digit Symbol Substitution Task, Letter Cancellation Task, digit span tasks and finger-tapping test). Within the 2 years, 29 subjects (32.2%) presented a conversion to dementia. The risk of conversion to dementia was associated with age and size of temporal lobe but not with gender, education, or apolipoprotein E4 genotype. Several neuropsychological measures were associated with the risk of conversion to dementia, but in a logistic regression performed with the significant variables found in the univariate analysis, only the Letter Cancellation Test was shown to be an independent predictor. In conclusion, the quite elevated conversion rates obtained show the usefulness, when defining MCI criteria, of considering not only memory impairment but also impairment in other cognitive areas, as well as mild impairment on higher-order activities of daily living. Among the variables considered, the Letter Cancellation Test proved to be a major predictor of short-term conversion to dementia.     

The rate of conversion of mild cognitive impairment to dementia: predictive role of depression

BACKGROUND: Mild cognitive impairment (MCI) is a condition referring to the persons with cognitive deficits measurable in some form or another, but not meeting criteria for dementia, and who have an increased risk of becoming demented. OBJECTIVE: To establish the rate of progression to dementia in MCI, to investigate the risk of conversion for amnestic vs multiple-domains subtypes, and to identify the predictors of progression. METHODS: MCI (n = 105) individuals enrolled in a longitudinal study received annual clinical and psychometric examinations for up to a mean of 3 years. The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted by a panel of specialists. RESULTS: After 3 years of follow-up, 23 of 105 subjects with MCI were diagnosed with dementia. 40 showed cognitive decline not dementia, 34 were stable and showed no cognitive decline or improvement, while eight showed cognitive improvement. CONCLUSIONS: We conclude that conversion rate from MCI to DSM-IIIR dementia was 21.9% over a period of 3 years. The occurrence of depressive symptoms may constitute a predictor for those who are more likely to progress to dementia. The risk of conversion to dementia was higher among the subjects with an evidence of impairment extending beyond memory than with those who suffered only from memory deficits, and the subjects who converted to dementia in this subtype had significantly higher baseline plasma total homocysteine levels than non-converters.     

Discriminative and predictive power of an informant report in mild cognitive impairment

BACKGROUND: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) requires caregivers to rate decline in patients' cognitive and functional performance and has never been used for mild cognitive impairment (MCI). METHODS: We contrasted the discriminative and predictive power of the IQCODE with that of the Mini Mental State Examination (MMSE) and a verbal episodic memory measure, the Rey's Auditory Verbal Learning Test (RAVLT), in 45 patients with MCI (mean (SD) age at baseline: 71.6 (4.7) years) and 30 outpatients with dementia (70.5 (6.3) years) attending the Neuropsychology Service, St Gerardo Hospital, and compared them with 55 cognitively intact elderly people (70.7 (7.1) years). Patients with MCI were followed up for at least 2 years or until conversion to dementia. RESULTS: In total, 24 patients with MCI (53.3%) had converted to dementia at follow up (mean (SD) duration of follow up 17.0 (7.3) months for converters and 35.0 (7.1) months for non-converters). At baseline, the ability to differentiate patients with MCI from healthy controls was similar for the IQCODE (area under the curve (AUC) 0.86) and the MMSE (AUC 0.84; z = 0.53, not significant). As predictors of conversion to dementia, a trend favouring the IQCODE (AUC 0.86) with respect to immediate (AUC 0.74) and delayed (AUC 0.75) recall on the RAVLT was apparent (z = 1.36, p = 0.087 versus immediate recall, z = 1.51, p = 0.064 versus delayed recall). The independent predictive ability of IQCODE and memory scores was evaluated through logistic regression, and the questionnaire alone yielded the best correct classification of 81%. CONCLUSIONS: The IQCODE is an informant based measure of cognitive decline that may provide a relevant contribution to the diagnostic and prognostic investigation of patients with MCI.     

Combining neuropsychological and structural neuroimaging indicators of conversion to Alzheimer's disease in amnestic mild cognitive impairment

Morphometric and neuropsychological retrospective studies of amnestic mild cognitive impairment (MCI) have demonstrated that regional atrophies and cognitive impairments may differentiate stable from progressing MCI. No measure has proved helpful prospectively. In this study, twenty five amnestic MCI patients and 25 healthy controls underwent structural MRI and comprehensive neuropsychological assessment. The groups' grey matter volumes were compared with voxel based morphometry and were also correlated with scores obtained on paired associates learning and category fluency tasks. MCI patients had significantly reduced grey matter volume in left mediotemporal and other neocortical regions compared with controls. Atrophy in perirhinal and anterior inferior temporal cortex was associated with poor scores on both category fluency and paired associates learning tasks. After 36 months, 44% of the MCI sample converted to dementia. Converter and non-converter MCI subgroups differed in paired associates learning and in category fluency scores, and showed limited differences in grey matter loss in the hippocampal complex. Variable atrophy in the hippocampus was not a relevant element in the converter/non converter distinction, but converters had significant volumetric reductions in the perhirinal cortex and in other anterior temporal and frontal neocortical areas. A high proportion of converters (91%) could be identified from baseline data using a combination of measures of regional atrophy in left temporal association cortex and poor scores on paired associates learning and category fluency tasks. This combined approach may offer a better option than using each measure alone to prospectively identify individuals at more immediate risk of conversion to dementia in the MCI population. The clinical advantage of this combination of structural MRI and neuropsychological measures in predicting conversion to dementia will need additional prospective validation.     

Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia

OBJECTIVE: To determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMH), whole-brain atrophy, and cardiovascular risk factors predict the development of cognitive decline and dementia. DESIGN: Subjects were recruited into this prospective cohort study and followed for incident cognitive decline for mean (SD) 6.0 (4.1) years. Magnetic resonance imaging dual-echo sequences, obtained at baseline, were used to determine the volume of WMH and the brain parenchymal fraction (BPF), the proportion of the intracranial cavity occupied by brain. White matter hyperintensity volume was analyzed as the percentage of intracranial volume (WMHr); "high WMH" was defined as a WMHr more than 1 SD above the mean. SETTING: General community. PATIENTS: Volunteer sample consisting of 67 subjects with normal cognition and 156 subjects with mild cognitive impairment (MCI). MAIN OUTCOME MEASURES: Time to diagnosis of MCI (among those with normal cognition at baseline) or time to diagnosis of dementia, either all-cause or probable Alzheimer disease (AD) (among those with MCI at baseline). Cox proportional hazards models were used for multivariable analysis. RESULTS: High WMH was a predictor of progression from normal to MCI (adjusted hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.33-8.17; P= .01) but not conversion from MCI to all-cause dementia. Conversely, BPF did not predict progression from normal to MCI but did predict conversion to dementia (adjusted HR, 1.10 for each 1% decrease in BPF; 95% CI, 1.02-1.19; P= .02). When conversion to AD dementia was considered as the outcome, BPF was likewise a predictor (adjusted HR, 1.16 for each 1% decrease in BPF; 95% CI, 1.08-1.24; P< .001), but high WMH was not. Past tobacco smoking was associated with both progression from normal to MCI (adjusted HR, 2.71; 95% CI, 1.12-6.55; P= .03) and conversion to all-cause dementia (adjusted HR, 2.08; 95% CI, 1.13-3.82; P= .02), but not AD dementia. CONCLUSIONS: These findings suggest that WMH are associated with the risk of progressing from normal to MCI. In persons whose cognitive abilities are already impaired, BPF predicts the conversion to dementia.     

Persistent mild cognitive impairment in geriatric depression

BACKGROUND: Cognitive impairment often occurs with geriatric depression and impairments may persist despite remission of depression. Although clinical definitions of mild cognitive impairment (MCI) have typically excluded depression, a neuropsychological model of MCI in depression has utility for identifying individuals whose cognitive impairments may persist or progress to dementia. METHODS: At baseline and 1-year follow-up, 67 geriatric patients with depression had a comprehensive clinical examination that included depression assessment and neuropsychological testing. We defined MCI by a neuropsychological algorithm and examined the odds of MCI classification at Year 1 for remitted depressed individuals with baseline MCI, and examined clinical, functional and genetic factors associated with MCI. RESULTS: Fifty-four percent of the sample had MCI at baseline. Odds of MCI classification at Year 1 were four times greater among patients with baseline MCI than those without. Instrumental activities of daily living were associated with MCI at Year 1, while age and APOE genotype was not. CONCLUSIONS: These results confirm previous observations that MCI is highly prevalent among older depressed adults and that cognitive impairment occurring during acute depression may persist after depression remits. Self-reported decline in functional activities may be a marker for persistent cognitive impairment, which suggests that assessments of both neuropsychological and functional status are important prognostic factors in the evaluation of geriatric depression.     

The impact of silent vascular brain burden in cognitive impairment in Parkinson’s disease

Background and purpose: White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer’s disease. Their effect in cognitive decline and dementia associated with Parkinson’s disease (PD) is still unclear. Methods: We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross‐sectional and follow‐up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2‐weighted MRI. The burden of WMHs was rated using the Scheltens scale. Results: No differences in WMHs were found between the three groups in the cross‐sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non‐demented patients re‐evaluated after a mean follow‐up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. Conclusions: White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies.     

Mild cognitive impairment.

Mild cognitive impairment (MCI) describes a state of cognitive functioning that is below defined norms, yet falls short of dementia in severity. It exists across a cognitive continuum with borders that are difficult to define precisely. Within our "graying" western societies, its prevalence increases with age. A number of subtypes of MCI, including age-associated memory impairment (AAMI), age-associated cognitive decline (AACD), amnestic MCI (MCIa), and cognitive impairment not dementia (CIND) have contributed to our understanding of MCI. Recent efforts have been directed at developing a uniform diagnostic classification for MCI that reflects the maturation of knowledge about this state. There is considerable etiological and clinical heterogeneity within MCI; however, there is a unifying increased risk of progression to dementia. The diagnostic process for MCI involves assessment of multiple cognitive domains, with particular attention to episodic and semantic memory, while neuroimaging with structural MRI and PET both add to the diagnostic and prognostic evaluation of MCI. Although there are no pharmacological treatments at present that are capable of delaying the long-term progression of MCI to dementia, there is some evidence of short-term symptomatic benefits with acetylcholinesterase inhibitors. MCI is an important clinical problem, which clinicians can expect to face with increasing frequency. The essentials of management include a thorough assessment directed at etiological determination and counseling and judicious use of available therapeutics.     

The new Alzheimer’s criteria in a naturalistic series of patients with mild cognitive impairment

To test the validity of the new diagnostic criteria for Alzheimer’s disease (AD) in a naturalistic series of patients with mild cognitive impairment (MCI). Ninety consecutive MCI patients were enrolled in a longitudinal study on the natural history of cognitive impairment. Medial temporal (MT) atrophy on MRI was defined as hippocampal volume below the fifth percentile of the distribution in healthy elders, abnormal CSF was based on Sjogren’s cutoffs for Abeta42 and tau, and temporoparietal hypometabolism on 18F-FDG PET based on Herholz’s t sum score. Patients were followed clinically to detect conversion to AD (MCI-AD), non-AD dementia (MCI-nAD), or no conversion (MCI-NC). The 24 MCI-AD and 15 MCI-nAD patients had sociodemographic, clinical, and neuropsychological baseline features similar to the 51 MCI-NC patients. All MCI patients with MT atrophy converted to AD, as did all those with abnormal CSF, but only 48 and 35% of those without MT atrophy or abnormal CSF converted (p on logrank test = 0.0007 and 0.001). Prediction of AD conversion was enhanced when positivity to either MT atrophy or abnormal CSF was considered, with only 15% of those MCI patients negative on both converting to AD (p < 0.0005). Markers were not predictive of non-AD dementia conversion. The accuracy of either MT atrophy or abnormal CSF in discriminating MCI-AD from MCI-NC was good (AUC 0.82, 95% CI 0.70–0.95). MT atrophy and abnormal CSF are the single most robust predictors of conversion to AD in MCI patients, and their combination enhances prediction. AD markers are not predictive of conversion to non-AD dementia.     

Prediction of 7‐year's conversion from subjective cognitive decline to mild cognitive impairment

Subjective cognitive decline (SCD) is a high‐risk yet less understood status before developing Alzheimer's disease (AD). This work included 76 SCD individuals with two (baseline and 7 years later) neuropsychological evaluations and a baseline T1‐weighted structural MRI. A machine learning‐based model was trained based on 198 baseline neuroimaging (morphometric) features and a battery of 25 clinical measurements to discriminate 24 progressive SCDs who converted to mild cognitive impairment (MCI) at follow‐up from 52 stable SCDs. The SCD progression was satisfactorily predicted with the combined features. A history of stroke, a low education level, a low baseline MoCA score, a shrunk left amygdala, and enlarged white matter at the banks of the right superior temporal sulcus were found to favor the progression. This is to date the largest retrospective study of SCD‐to‐MCI conversion with the longest follow‐up, suggesting predictable far‐future cognitive decline for the risky populations with baseline measures only. These findings provide valuable knowledge to the future neuropathological studies of AD in its prodromal phase.     

Rates of progression in mild cognitive impairment and early Alzheimer's disease

OBJECTIVE: To compare rates of progression in the very mildest stages of AD, including the stage currently identified as mild cognitive impairment (MCI), and to identify predictors of those rates. METHODS: Demented (n = 289) and nondemented (n = 230) individuals enrolled in longitudinal studies at an Alzheimer Disease Research Center received annual clinical and psychometric examinations for up to 20 years. In order of increasing dementia severity, demented individuals were diagnosed with incipient, very mild, or mild dementia; the incipient stage is equivalent to MCI. Outcome measures included death, nursing home placement, and psychometric scores. RESULTS: Rate of progression increased with dementia severity as staged by the Clinical Dementia Rating at entry into the study. With respect to the dichotomous outcomes, the increase with dementia severity was more dramatic for the endpoint of nursing home entry than it was for the endpoint of death. Increased rates of cognitive decline with increased dementia severity were also obtained for psychometric scores. There was limited evidence of other predictors of progression. CONCLUSIONS: The lack of effective predictors of the rate of dementia progression extends to the very earliest stages of the disease, including what is often called MCI. A new approach to the identification of correlates of rates of progression is needed.     

A voxel based morphometry study on mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. OBJECTIVE: To study the pattern of brain atrophy in MCI. METHODS: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p < 0.001. RESULTS: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere-for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. CONCLUSIONS: The MRI findings in MCI resemble those seen in early AD.     

FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment

The accurate prediction, at a pre-dementia stage of Alzheimer's disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment.     

Asymptomatic spontaneous cerebral emboli and cognitive decline in a cohort of older people: a prospective study

BACKGROUND: Asymptomatic spontaneous cerebral emboli (SCE) are common in dementia and are associated with cognitive decline in dementia. The significance of their presence in older people is unknown. METHOD: We included 96 participants (mean (SD) age 76.8 (6.7) years, 46% female) who were the control group in a case-control study to evaluate SCE in dementia. Cognitive functioning was assessed prospectively over 2.5 years, using the MMSE and CAMCOG. RESULTS: The mean (SD) MMSE score was 28.7 (1.4) at baseline with an average (SD) drop of 0.79 (0.91) per year. The presence of SCE was not related to the annual drop in MMSE score, nor to the CAMCOG score at follow-up (p = 0.88 and p = 0.41, respectively). Linear regression analyses identified higher age in years (beta = 0.29, p = 0.003), history of stroke (beta = 0.31, p = 0.001) and carotid stenosis (beta = 0.28, p = 0.003) as independent predictors of cognitive decline. CONCLUSION: We found no association between the presence of SCE and subsequent cognitive decline in older people without dementia.     

FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment

The accurate prediction, at a pre-dementia stage of Alzheimer’s disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment.     

FDG-PET and CSF phospho-tau for prediction of cognitive decline in mild cognitive impairment

Specific patterns of cortical glucose metabolism disturbances and increased CSF phospho-tau (p-tau(181)) concentrations could be demonstrated to predict cognitive decline and shift to dementia in amnestic mild cognitive impairment (MCI). But comparisons of both diagnostic tools have not been undertaken so far. The aim of the study was to compare (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) findings and CSF phospho-tau (p-tau(181)) measurements in the prediction of cognitive deterioration and conversion to dementia in MCI. During follow-up (mean 19 months) eight of 16 patients (50%) showed progressive cognitive decline, and four patients shifted to dementia. Pathological FDG-PET and elevated p-tau(181) levels both predicted deterioration. While p-tau(181) was highly sensitive for cognitive decline, FDG-PET was superior in predicting conversion to clinical dementia in MCI patients.     

Cerebral white matter hyperintensities in the prediction of cognitive decline and incident dementia

Abstract

Cerebral white matter hyperintensities (WMH), detected in vivo with magnetic resonance imaging (MRI), are commonly used to assess cerebrovascular burden in cognitive impairment. However, the association between WMH and cognition is not consistent across the literature. The present review examines evidence from published longitudinal studies. We reviewed the PubMed data base from January 1990 to March 2013 and included studies investigating the association of WMH with (1) the risk of dementia in the general population, (2) the risk of conversion to dementia in the mild cognitive impairment (MCI) population, and (3) cognitive decline in the general population. WMH were associated with all types of dementia in the general population, but not in MCI patients. Results are discrepant for global decline. WMH appear to be early predictors of the risk of dementia, but this association appears to be modulated by cognitive reserve, age and the spatial distribution of lesions. There are, however, some limits in the use of WMH as a marker of vascular burden. In addition to their ischaemic origin, WMH may be the result of co-occurring morbidity. Further research is needed to elucidate to what extent WMH actually reflect vascular risk to evaluate the likely efficacy of interventions specifically targeting WMH reduction.     

Brain MRI hippocampal volume and prediction of clinical status in a mild cognitive impairment trial

Mild Cognitive Impairment (MCI) is considered a transitional stage in the pathogenesis of Alzheimer’s disease; however, not all MCI patients progress to clinically defined AD or decline at identical rates. Hippocampal atrophy, as measured by Magnetic Resonance Imaging (MRI), may be a marker for hippocampal pathology in patients with MCI and predict a more rapid deterioration to clinical AD. In this study, we used MRI data from an ongoing MCI clinical trial to determine whether MRI hippocampal volume at baseline was associated with cognitive and functional performance in MCI subjects and whether it predicted those individuals who were more likely to develop AD. We performed correlational analyses between the MRI hippocampal volumes at study entry and the subjects’ concurrent performance on neuropsychological measures and clinical ratings. Larger hippocampal volume was associated with better performance on tests of memory, general cognition, and overall clinical ratings. Further analyses suggested that a smaller baseline hippocampal volume may be associated with a higher risk of developing clinical AD. As the trial is still ongoing, these results require confirmation once the trial is completed. In summary, these data suggest that MRI hippocampal volume may be a useful correlate of disease severity in MCI subjects and a prognostic indicator of subsequent AD.