Subjective Memory Impairment Research Articles

Concordance between Subjective and Objective Memory Impairment in Volunteer Subjects.

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. 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. 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 Examination scores ≥27, and returned to complete a comprehensive diagnostic assessment. 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). 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.

Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment.

To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. Randomized, double-blind, placebo-controlled study. Academic medical center. Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p ≤ 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge.

The Utility of the Addenbrooke's Cognitive Examination Version Three in Early-Onset Dementia

Background/Aims: Early-onset dementia (EOD) is defined as functionally relevant cognitive decline with age of onset at less than 65 years. The aim of this study was to investigate the utility of the recently validated third version of the Addenbrooke's Cognitive Examination (ACE-III) in predicting dementia diagnoses in EOD. Methods: ACE-III scores of EOD patients were compared to those of healthy controls (HC) and individuals with subjective memory impairment (SMI). Results: The study included 71 EOD patients (Alzheimer's disease, n = 31; primary progressive aphasia, n = 11; behavioural-variant frontotemporal dementia, n = 18, and posterior cortical atrophy, n = 11); there were 28 HC and 15 individuals with SMI. At a cut-off score of 88/100, the ACE-III displayed high sensitivity and specificity in distinguishing EOD from HC (91.5 and 96.4%) and SMI (91.5 and 86.7%). Conclusions: The ACE-III is a reliable cognitive screening tool in EOD.

Subjective spatial navigation complaints are associated with regional brain atrophy and APOE in elderly with subjective memory impairment

Subjective spatial navigation complaints are associated with regional brain atrophy and APOE in elderly with subjective memory impairment

FUNCTIONAL MEMORY SYMPTOMS

Dr Jon Stone is an NHS Consultant Neurologist and Honorary Senior Lecturer in Neurology in Edinburgh. He has had a research interest in functional disorders in neurology since 1999 starting...

123I-MIBG myocardial scintigraphy and neurocirculatory abnormalities in patients with dementia with Lewy bodies and Alzheimer's disease

BackgroundAlthough adoption of new clinical criteria for dementia with Lewy bodies (DLB) leads to an increase in the proportion of patients diagnosed with probable DLB, the sensitivity of clinical diagnostic criteria of DLB is low, and there are no generally accepted clinical or imaging biomarkers to distinguish DLB from other types of dementia. In this study, we investigated whether neurocirculatory abnormalities and cardiac sympathetic denervation differed in controls and patients with subjective memory impairment (SMI), mild cognitive impairment (MCI), Alzheimer's disease (AD), and DLB. We also assessed whether spontaneous features of Parkinsonism might be related to the neurocirculatory abnormalities and cardiac sympathetic denervation found in DLB. MethodsTwenty-two consecutive patients with probable DLB were enrolled in this study; 25 age-matched controls, 14 SMI, 24 MCI, and 37 AD patients were also evaluated. Metaiodobenzylguanidine (MIBG) uptake was assessed using the ratio of the heart to the upper mediastinum (H/M ratio), and orthostatic vital signs and ambulatory 24-hour blood pressure monitoring values were recorded. ResultsThe mean H/M ratio was significantly lower and the proportion of orthostatic hypotension was higher in patients with DLB than in controls, SMI, MCI and AD patients. In patients with DLB, spontaneous Parkinsonism was not related to the degree of cardiac sympathetic denervation nor did it influence neurocirculatory abnormalities. ConclusionOur results suggest that MIBG scintigraphy and autonomic function tests may be useful for distinguishing between DLB and AD in clinical practice. Myocardial postganglionic sympathetic denervation and autonomic dysfunctions are present in patients with DLB regardless of spontaneous Parkinsonism.

Excessive daytime sleepiness is related to subjective memory impairment in late life: a cross-sectional community-based study.

The aim of this study was to determine whether daytime sleepiness is related to subjective memory impairment among community-dwelling elderly people, after adjustment for psychosocial variables. Questionnaires were mailed to all 5199 elderly residents living in one area of Tokyo. The questionnaires collected information about sociodemographic variables, subjective memory impairment, and excessive daytime sleepiness, which was measured by the Japanese version of the Epworth Sleepiness Scale. Information was also collected on sleep hygiene, health-related variables, and psychosocial variables, including perceived social support, social withdrawal, and work status. Of the 4783 questionnaires that were returned (92.0%), 4185 participants were included in the analysis (valid response rate: 80.5%), after the exclusion of questionnaires with missing data. The average score on the Japanese version of the Epworth Sleepiness Scale was 5.0 ± 3.9 for men and 4.5 ± 3.7 for women. The frequency of excessive daytime sleepiness was 8.3% for men, 5.8% for women, and 7.0% in total. Stepwise multivariate logistic regression revealed the odds ratio of excessive daytime sleepiness as a predictor of subjective memory impairment was 6.06 (95% confidence interval; 3.06-12.03). Elderly people who complain of daytime sleepiness are potential candidates for interventions related to dementia care after careful consideration of other possible causes of sleepiness.

Mild Cognitive Impairment: Structural, Metabolical, and Neurophysiological Evidence of a Novel EEG Biomarker.

Recent studies demonstrate that the alpha3/alpha2 power ratio correlates with cortical atrophy, regional hypoperfusion, and memory impairment in subjects with mild cognitive impairment (MCI). Evidences were reviewed in subjects with MCI, who underwent EEG recording, magnetic resonance imaging (MRI) scans, and memory evaluation. Alpha3/alpha2 power ratio (alpha2 8.9-10.9 Hz range; alpha3 10.9-12.9 Hz range), cortical thickness, linear EEG coherence, and memory impairment have been evaluated in a large group of 74 patients. A subset of 27 subjects within the same group also underwent single photon emission computed tomography (SPECT) evaluation. In MCI subjects with higher EEG upper/low alpha power ratio, a greater temporo-parietal and hippocampal atrophy was found as well as a decrease in regional blood perfusion and memory impairment. In this group, an increase of theta oscillations is associated with a greater interhemispheric coupling between temporal areas. The increase of alpha3/alpha2 power ratio is a promising novel biomarker in identifying MCI subjects at risk for Alzheimer's disease.

V43. Vagus somatosensory evoked potentials in elderly: A potential risk marker for neurodegeneration and its relation to Subjective Memory Impairment

Background Vagus somatosensory evoked potentials (VSEP) have been shown to have higher latencies with aging, which are even more increased in patients with neurodegenerative or demyelination diseases, which may be related to an early affection of the brain stem and especially of the nuclei of the vagus nerve. Patients with Alzheimer’s disease and subjects with mild cognitive impairment as well as patients with Parkinson’s disease have increased latencies compared to age-matched healthy controls. A further potential risk or prodromal marker for Alzheimer’s (AD) disease being recently focused is subjective memory impairment (SMI). A main research question is which marker has the best predictive value for degenerative processes like AD. We investigate this question from both a psychological (SMI) and biological (VSEP) perspective. Methods The association of VSEP latencies and SMI is studied in a healthy risk cohort, including 358 elderly subjects, who are in a longitudinal study of risk factors for neurodegenerative disorders (TREND study, Tuebinger evaluation of Risk factors for the Early detection of NeuroDegeneration). Results The results show increased VSEP latencies for peak P2 at Fz-F4 in subjects who report SMI and are worried about it, as compared to subjects who report memory impairment, but are not concerned and to subjects without complaints. These results are in line with the findings during the last years of increased VSEP latencies in neurodegenerative diseases. Conclusion VSEP are easily and comfortably measureable evoked potentials which may have a correlation to neurodegenerative or demyelinating damage to the brainstem nuclei of the N. Vagus. An important implication of the results is to further examine the predictive value of VSEP for neurodegenerative processes in longitudinal perspective. The present results support a potential role of VSEP for the detection of very early neurodegenerative processes which may precede Alzheimer’s disease.

P3‐100: The distribution and clinical impact of apolipoprotein e4 among patients with subjective memory impairment and early mild cognitive impairment

P3‐100: The distribution and clinical impact of apolipoprotein e4 among patients with subjective memory impairment and early mild cognitive impairment

Predictors of Clinical Progression of Subjective Memory Impairment in Elderly Subjects: Data from the Clinical Research Centers for Dementia of South Korea (CREDOS)

Background/Aims: The aims of this study were to determine baseline factors related to the progression of subjective memory impairment (SMI) in elderly subjects and to develop a new modeling scale to predict progression. Methods: Elderly subjects with SMI were recruited from the nationwide Clinical Research Centers for Dementia of South Korea (CREDOS) multicenter cohort and divided into two groups: (1) progressed to mild cognitive impairment or Alzheimer's disease or (2) stable without progression. Baseline clinical characteristics were compared between the groups, and the most relevant predictors of progression were assessed. A new modeling scale combining the predictors was developed. Results: In total, 129 subjects with SMI were analyzed. The follow-up duration was 0.5-4.7 years, and the median time to event was 3.64 years. The progressing group (n = 29) differed from the stable group (n = 100) in terms of baseline age, apolipoprotein E4 (APOE4) status, and some cognitive domains. Older age, a lower Mini-Mental State Examination recall score, APOE4 carrier, and a lower verbal delayed recall score were the most relevant predictors of progression, and a new modeling scale with these 4 predictors provided a better explanation of progression. Conclusion: SMI subjects with a higher risk of progression can be identified using a new modeling scale and might need further evaluations and more frequent follow-up.

Subjective memory impairment: No suitable criteria for case-finding of dementia in primary care

IntroductionSubjective memory impairment (SMI) might be used for the case-finding of dementia. Present analyses aim to determine the diagnostic value and the predictive ability of SMI and related worries for the discrimination of patients screened positive or negative for dementia. MethodsThe analyses are based on data derived from the ongoing German general practioner (GP)-based, randomized controlled trial DelpHi-MV. A total of 5106 patients (age ≥ 70, living at home) were first asked for SMI and related worries and then screened for dementia in 110 participating GP practices (November 2011 to August 2014; preliminary data) using the DemTect. ResultsA total number of 2556 patients (50%) stated that they experience SMI and 892 patients (17%) screened positive for dementia. The sensitivity of SMI for the correct classification of positively screened patients was 54%, the positive predictive value (PPV) 19%. The specificity of SMI was 51%; the negative predictive value (NPV) 84%. Among 2480 patients with SMI, 45% reported SMI-related worries (sensitivity 52%; specificity 57%; PPV 22%; NPV 84%). Receiver operating characteristics analyses showed no statistically significant improvement in the area under the curves when using SMI or related worries as predictors (additional to age and sex) for the discrimination between positively and negatively screened patients. DiscussionThe analyses showed that the risk of overlooking cognitive impairment in the subgroup of patients who state that they do not experience SMI would be unreasonable high. Thus, the results provide clear evidence that neither SMI nor related worries can be used as a valid criteria to decide whether an elderly primary care patient should be tested for dementia.Trials registration: ClinicalTrials.gov Identifier: NCT01401582.

Discriminative power of the advanced activities of daily living (a-ADL) tool in the diagnosis of mild cognitive impairment in an older population.

Mild cognitive impairment (MCI) is characterized by subjective and objective memory impairments in the absence of manifest functional decline. Mild changes in activities of daily living (ADL) can be present and probably predict conversion to dementia. A new advanced (a)-ADL tool was developed, evaluating high-level activities and, taking each participant as their own reference, distinguishing a global Disability Index (a-ADL-DI), a Cognitive Disability Index (a-ADL-CDI), and a Physical Disability Index (a-ADL-PDI), based on the number of activities performed and the severity and causes of the functional problem. This study evaluates the discriminative validity of the a-ADL in MCI. Based upon clinical evaluation and a set of global, cognitive, mood, and functional assessments, 150 community-dwelling participants (average age 80.3 years (SD 5; 66-91)) were included and diagnosed as (1) cognitively healthy participants (n = 50); (2) patients with a-MCI (n = 48), or (3) mild to moderate AD (n = 52). The a-ADL tool was not a part of the clinical evaluation. The a-ADL-DI and the a-ADL-CDI showed a sensitivity and specificity ranging from 70% to 94.2%, Positive Predictive Value ranging from 70% till 93.8%, and Negative Predictive Value from 64.4% and 93.8%, an area under the curve (AUC) ranging from 0.791 to 0.960. Functional decline related to physical deficits, as assessed by the a-ADL-PDI, did not discriminate between the different groups. The a-ADL tool has a good ability to distinguish normal and pathological cognitive aging. Its discriminative power for underlying causes of limitations may be an advantage.

Assessment of everyday memory functioning in temporal lobe epilepsy and healthy adults using the multifactorial memory questionnaire (MMQ)

Temporal lobe epilepsy (TLE) is associated with differing degrees of objective and subjective memory impairment. Memory self-report is an important part of the assessment process but few reliable and valid measures have been researched with this group. We thus aimed to explore subjective impairments with a robust measure: the multifactorial memory questionnaire (MMQ; Troyer and Rich, 2002). This was administered to 82 people with TLE and an age and education matched control group of the same size. The questionnaire probes worries about memory (MMQ-contentment); subjective forgetfulness (MMQ-ability); and use of compensatory strategies (MMQ-strategy). The TLE group reported significantly more worries about their memory, more instances of forgetfulness and use of more strategies than control participants. Strategy use was related to demographic factors in controls but not in the TLE group. Analysis of epilepsy related factors indicated that hemispheric laterlisation subgroups did not differ from one another on any subscale, nor did participants grouped according to their use of one, several, or no anti-epileptic medications. Measures of chronicity including age of onset and illness duration also failed to correlate with the MMQ subscales. Because objective memory performance is often impaired in more chronic and intractable cases, the lack of difference in subjective complaint is surprising and warrants future research to examine the relationship between this questionnaire and standardized test scores. We conclude that the MMQ is a clinical measure that could be used either outside or in tandem with neuropsychological assessment to gauge everyday memory difficulties among epilepsy patients.

Distinct Patterns and Clinical Implications of Semantic Memory Deterioration Among Patients With MCI.

Limited research has investigated the effects of executive dysfunction on semantic memory deterioration among patients with amnestic mild cognitive impairment (aMCI). This study examined the cognitive performance of 181 participants from various MCI subgroups, a group of mildly impaired individuals with dementia of the Alzheimer type (DAT) and a group of individuals with subjective memory impairment on various semantic memory tasks. The aMCI-single domain (aMCI-sd) group displayed poor performance on a semantic memory task requiring relatively higher degrees of effortful retrieval, and participants in the aMCI-multiple domain (aMCI-md) group, who also suffered with mild executive dysfunction displayed poor performance on all semantic memory tasks, similar to the DAT group. The nonamnestic MCI (non-a-MCI)-single domain group displayed normal performance across all semantic tasks, whereas the non-a-MCI-multiple domain group displayed a pattern similar to that of the aMCI-sd group. aMCI-sd patients who displayed poor performance on the semantic memory task had higher risk of conversion to DAT, whereas poor performance on tasks requiring relatively less effortful retrieval was associated with higher risk of conversion in the aMCI-md group. Thus, executive function may relate to deterioration of semantic memory retrieval processes. Such patterns of semantic memory impairment could be valuable for characterization of cognitive differences among MCI patients.

CSF biomarkers for the differential diagnosis of Alzheimer's disease: A large-scale international multicenter study

IntroductionThe aim of this study was to test the diagnostic value of cerebrospinal fluid (CSF) beta-amyloid (Aβ1–42), phosphorylated tau, and total tau (tau) to discriminate Alzheimer's disease (AD) dementia from other forms of dementia. MethodsA total of 675 CSF samples collected at eight memory clinics were obtained from healthy controls, AD dementia, subjective memory impairment, mild cognitive impairment, vascular dementia, Lewy body dementia (LBD), fronto-temporal dementia (FTD), depression, or other neurological diseases. ResultsCSF Aβ1–42 showed the best diagnostic accuracy among the CSF biomarkers. At a sensitivity of 85%, the specificity to differentiate AD dementia against other diagnoses ranged from 42% (for LBD, 95% confidence interval or CI = 32–62) to 77% (for FTD, 95% CI = 62–90). DiscussionCSF Aβ1–42 discriminates AD dementia from FTD, but shows significant overlap with other non-AD forms of dementia, possibly reflecting the underlying mixed pathologies.

Subjective memory impairment and well-being in community-dwelling older adults.

The relationship between subjective memory impairment (SMI), future cognitive decline, and negative health status provides an opportunity for interventions to reduce memory complaints in high-risk groups. This study aimed to examine the relationship between SMI and indicators of well-being in older adults enrolled in an exercise trial. Additionally, the study examined whether two different modes of exercise training, aerobic walking and non-aerobic flexibility, toning, and balance, differentially influenced subjective memory across the trial. Community-dwelling older adults (n = 179, mean age = 66.4 years) were randomly assigned to a walking or flexibility, toning, and balance group for 12 months. Subjective memory, happiness, perceived stress, and symptom reporting were measured at baseline, 6 months, and 12 months. A main effect of subjective memory indicated that individuals with the fewest memory complaints had lower perceived stress (P < 0.001), lower physical symptom reporting (P < 0.001), and higher happiness levels (P < 0.001) across all measurement occasions. Both main and interaction effects of time and group on SMI were not significant, suggesting SMI remained stable across the intervention and was not significantly impacted by participation in exercise training. SMI was not responsive to exercise interventions, and the relationship between SMI and negative well-being demonstrates a need for interventions to reduce memory complaints in high-risk groups.

Cortical thinning in individuals with subjective memory impairment.

Elderly individuals with subjective memory impairment (SMI) report memory decline, but perform within the age-, gender-, and education- adjusted normal range on neuropsychological tests. Longitudinal studies indicate SMI as a risk factor or early sign of Alzheimer's disease (AD). There is increasing evidence from neuroimaging that at the group level, subjects with SMI display evidence of AD related pathology. This study aimed to determine differences in cortical thickness between individuals with SMI and healthy control subjects (CO) using the FreeSurfer environment. 110 participants (41 SMI/69 CO) underwent structural 3D-T1 MR imaging. Cortical thickness values were compared between groups in predefined AD-related brain regions of the medial temporal lobe, namely the bilateral entorhinal cortex and bilateral parahippocampal cortex. Cortical thickness reduction was observed in the SMI group compared to controls in the left entorhinal cortex (p = 0.003). We interpret our findings as evidence of early AD-related brain changes in persons with SMI.

Subjective memory impairment points to future risk of dementia

Subjective memory impairment points to future risk of dementia

Impact of Apolipoprotein E4 Polymorphism on the Gray Matter Volume and the White Matter Integrity in Subjective Memory Impairment without White Matter Hyperintensities: Voxel-Based Morphometry and Tract-Based Spatial Statistics Study under 3-Tesla MRI.

The aim of this study is to compare gray matter (GM) volume and white matter (WM) integrity in Apolipoprotein E4 (ApoE ε4) carriers with that of ApoE ε4 noncarriers using the voxel-based morphometry and diffusion tensor imaging (DTI) to investigate the effect of the ApoE ε4 on brain structures in subjective memory impairment (SMI) without white matter hyperintensities (WMH). Altogether, 26 participants with SMI without WMH were finally recruited from the Memory impairment clinics of Pusan National University Hospital in Korea. All participants were ApoE genotyped (ApoE ε4 carriers: n = 13, matched ApoE ε4 noncarriers: n = 13) and underwent 3-tesla magnetic resonance imaging (MRI) including 3-dimensional volumetric images for GM volume and DTI for WM integrity. ApoE ε4 carriers compared with noncarriers in SMI without WMH showed the atrophy of GM in inferior temporal gyrus, inferior parietal lobule, anterior cingulum, middle frontal gyrus, and precentral gyrus and significantly lower fractional anisotropy WM values in the splenium of corpus callosum and anterior corona radiate. Our findings suggest that the ApoE ε4 is associated with both atrophy of GM volume and disruption of WM integrity in SMI without WMH.