Brain Morphometric Correlates of Depressive Symptoms among Patients with and without Dementia.

Introduction: Findings regarding brain morphometry among patients with dementia and concomitant depressive symptoms have been inconsistent. Thus, the aim of the present study was to test the hypothesis that dementia and concomitant depressive symptoms are associated with structural brain changes in the temporal lobe measured with structural magnetic resonance imaging (MRI). Methods: A sample of 492 patients from Norwegian memory clinics (n = 363) and Old Age Psychiatry services (n = 129) was studied. The assessment included the Cornell Scale for Depression in Dementia (CSDD), Instrumental Activities of Daily Living Scale, Mini Mental State Examination, and MRI of the brain, processed with FreeSurfer to derive ROI measures of cortical thickness, volume, and area using the Desikan-Killiany parcellation, as well as subcortical volumes. Dementia was diagnosed according to ICD-10 research criteria. Correlates of brain morphometry using multiple linear regression were examined. Results: Higher scores on the CSDD were associated with larger cortical volume (ß = 0.125; p value = 0.003) and area of the left isthmus of the cingulate gyrus (ß = 0.151; p value = <0.001) across all patients. Inclusion of an interaction term (dementia × CSDD) revealed a smaller area in the left temporal pole (ß = -0.345; p value = 0.001) and right-transverse temporal cortex (ß = -0.321; p value = 0.001) in patients with dementia and depressive symptoms. Discussion/Conclusion: We confirm the previous findings of structural brain changes in temporal regions among patients with dementia and concomitant depressive symptoms. This may contribute to a better understanding of the mechanisms underlying depression in dementia. To the best of our knowledge, this is the largest study conducted on this topic to date.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment and Alzheimer's disease with dementia.

We present associations between neuropsychiatric symptoms (NPS) and brain morphology in a large sample of patients with mild cognitive impairment (MCI) and Alzheimer's disease with dementia (AD dementia).Several studies assessed NPS factor structure in MCI and AD dementia, but we know of no study that tested for associations between NPS factors and brain morphology. The use of factor scores increases parsimony and power. For transparency, we performed an additional analysis with selected Neuropsychiatric Inventory - Questionnaire (NPI-Q) items. Including regional cortical thickness, cortical and subcortical volumes, we examined associations between NPS and brain morphology across the whole brain in an unbiased fashion. We reported both statistical significance and effect sizes, using linear models adjusted for multiple comparisons by false discovery rate (FDR). Moreover, we included an interaction term for diagnosis and could thereby compare associations of NPS and brain morphology between MCI and AD dementia.We found an association between the factor elation and thicker right anterior cingulate cortex across MCI and AD dementia. Associations between the factors depression to thickness of the banks of the left superior temporal sulcus and psychosis to the left post-central volume depended on diagnosis: in MCI these associations were positive, in AD dementia negative.Our findings indicate that NPS in MCI and AD dementia are not exclusively associated with atrophy and support previous findings of associations between NPS and mainly frontotemporal brain structures. OBJECTIVES: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and Alzheimer's disease with dementia (AD dementia), but their brain structural correlates are unknown. We tested for associations between NPS and MRI-based cortical and subcortical morphometry in patients with MCI and AD dementia. DESIGN: Cross-sectional. SETTINGS: Conducted in Norway. PARTICIPANTS: Patients with MCI (n = 102) and AD dementia (n = 133) from the Memory Clinic and the Geriatric Psychiatry Unit at Oslo University Hospital. MEASUREMENTS: Neuropsychiatric Inventory ­ Questionnaire (NPI-Q) severity indices were reduced using principal component analysis (PCA) and tested for associations with 170 MRI features using linear models and false discovery rate (FDR) adjustment. We also tested for differences between groups. For transparency, we added analyses with selected NPI-Q items. RESULTS: PCA revealed four factors: elation, psychosis, depression, and motor behavior.FDR adjustment revealed a significant positive association (B = 0.20, pFDR < 0.005) between elation and thickness of the right caudal anterior cingulate cortex (ACC) across groups, and significant interactions between diagnosis and psychosis (B = −0.48, pFDR < 0.0010) on the left post-central volume and between diagnosis and depression (B = −0.40, pFDR < 0.005) on the thickness of the banks of the left superior temporal sulcus. Associations of apathy, anxiety, and nighttime behavior to the left temporal lobe were replicated. CONCLUSIONS: The positive association between elation and ACC thickness suggests that mechanisms other than atrophy underly elation. Interactions between diagnosis and NPS on MRI features suggest different mechanisms of NPS in our MCI and AD dementia samples. The results contribute to a better understanding of NPS brain mechanisms in MCI and AD dementia.

Locus of Control and Its Associations with Depressive Symptoms amongst People with Dementia.

INTRODUCTION: Depression is common amongst people with dementia. This study examines whether locus of control (LoC), a perceived control construct influential in the coping process, is related to depressive symptoms in this population. METHODS: In this prospective observational study, 257 community-dwelling older adults with a confirmed dementia diagnosis were included. At baseline, measures of depressive symptoms, LoC, cognition, independent functional ability, general health, dementia severity, and dementia disease insight were collected. At follow-up, measures of depressive symptoms and cognition were collected. Multiple linear regression using degree of depressive symptoms as measured with Montgomery-Asberg Depression Rating Scale as a dependent variable was applied to assess whether LoC was associated with depressive symptoms at baseline and follow-up while controlling for covariates. RESULTS: LoC (p < 0.001), general health (p = 0.003), and insight (p = 0.010) were associated with severity of depressive symptoms at baseline, accounting for 28% of the variance. LoC (p = 0.025) and depressive symptoms (p < 0.001) at baseline were associated with severity of depressive symptoms at follow-up, accounting for 56.3% of the variance. CONCLUSION: LoC was significantly associated with severity of depressive symptoms in people with dementia at baseline and at follow-up. Attention to LoC may be valuable for our understanding of depression in people with dementia, and interventions targeting depression could benefit from including a focus on internalizing perceived control. However, these findings are novel, and more research is needed.

Control Beliefs among People with Dementia: A Systematic Review.

INTRODUCTION: Dementia diseases are still incurable, and in order to assist in living well with the disease, researchers are increasing their attention to the value of control beliefs. Control beliefs are associated with coping and psychological well-being; however, knowledge on how they relate to well-being outcomes in people with dementia is limited. This review aimed to synthesize knowledge about control beliefs in this group to guide future interventions and research. METHOD: A systematic search of 6 databases (MEDLINE, CINAHL, PsychINFO, AgeLine, Embase, and the Cochrane Library) with broad search terms related to dementia, control, and coping was conducted. Studies that investigated people with a confirmed dementia diagnosis and that used a questionnaire to measure control beliefs quantitatively were included. RESULTS: Eighteen studies were identified, examining self-efficacy, personal control/mastery, or locus of control. The studies varied in aim and design, with fair to good methodological quality. However, 10 studies included <50 participants with dementia, leaving findings unreliable due to low power. Participants with dementia in the mild to moderate stages were included, with average age in the seventies. Except for one validation study, the control belief questionnaires had not been validated for people with dementia. CONCLUSION: There is a lack of knowledge about control beliefs among people with dementia, due to few and low-powered studies. Although we cannot conclude regarding control beliefs, our findings support the feasibility of quantitative research on control beliefs among people with dementia and we recommend that they be included in this type of research.

One-Year Change in Locus of Control among People with Dementia.

INTRODUCTION: Knowledge of how perceptions of personal control change over time may provide valuable insights into how people cope with having dementia. The present study aimed to examine change in locus of control over a 12-month period in persons with dementia. METHOD: The study included 52 participants with dementia. Locus of control was measured with the Locus of Control of Behavior Scale (LoCB), with higher scores indicating a more external locus of control, interpreted as perceiving less personal control. A ≥5% change on the LoCB was considered clinically meaningful. We recorded sociodemographic characteristics and assessed dementia severity, cognition, ability to function independently in daily activities and physical self-maintenance, depressive symptomatology, and number of prescribed medications. Analyses were performed to examine differences between those with increases (more external) or decreases (less external) in the LoCB score after 12 months and to examine associations between baseline variables and change in the LoCB score. RESULTS: The mean LoCB score for the total sample did not change after 12 months (baseline mean 29.33 vs. follow-up mean 30.33, p = 0.553); however, 2 subgroups emerged. Using the ≥5% cutoff revealed that the LoCB score changed for 92.3% of the sample, becoming less external (lower LoCB) for 21 participants and more external (higher LoCB) for 27 participants. At baseline, the mean LoBC score was higher in the group that became less external (33.81 vs. 24.56), p = 0.006, while this was reverse at follow-up (23.57 vs. 34.41), p = 0.001. Dementia severity and dependence in physical self-maintenance increased during the 12 months in both groups. Among those becoming more external, we also found a decline in cognition (p = 0.002), an increase in dependence in daily activities (p = 0.003), an increase in the use of prescribed medication, and a decrease in depressive symptomatology (p = 0.003). The baseline LoCB score was the only variable associated with 12-month change in LoCB scores (p = 0.001). CONCLUSION: Most participants showed a clinically meaningful change in locus of control after 12 months. Those with more signs of dementia progression reported a decrease in personal control but also a decrease in depressive symptoms. These findings are interesting for our understanding of coping but must be replicated with a larger sample.

Young- and Late-Onset Dementia: A Comparative Study of Quality of Life, Burden, and Depressive Symptoms in Caregivers.

OBJECTIVE: To compare the quality of life, burden, and depressive symptoms of caregivers of individuals with young-onset dementia (YOD) and late-onset dementia (LOD). METHODS: Using a cross-sectional design, a convenience sample of 110 dyads of individuals with dementia and their caregivers, all living in the community, was included. The care recipients completed assessments about cognition, quality of life, and awareness of disease. Caregivers' quality of life, resilience, depressive and anxiety symptoms, hopelessness, and burden of care were assessed. RESULTS: A significant difference was found in caregivers' burden and depressive symptoms according to the age of onset. However, there was no difference in caregivers' quality of life between YOD and LOD groups. In both groups, a linear regression analysis indicated that caregivers' perspective of quality of life of care recipient and caregivers' hopelessness were associated with their quality of life. In addition, in the LOD group, caregivers' burden was associated with their perspective of the quality of life of care recipient, type of kinship, and presence of emotional problems. In the YOD group, caregivers' burden was associated with duration of caregiving role, cohabitating with care recipient, and their anxiety symptoms. Caregivers' depressive symptoms were associated with anxiety symptoms in the YOD group, whereas hopelessness was associated with caregivers' depressive symptoms in both the groups. CONCLUSION: Our findings suggest that the factors that affect quality of life, burden, and depressive symptoms of caregivers of individuals with LOD differ from those that affect the caregivers of individuals with YOD.

The Power of EEG to Predict Conversion from Mild Cognitive Impairment and Subjective Cognitive Decline to Dementia.

INTRODUCTION: The aim of this study was to examine if quantitative electroencephalography (qEEG) using the statistical pattern recognition (SPR) method could predict conversion to dementia in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: From 5 Nordic memory clinics, we included 47 SCD patients, 99 MCI patients, and 67 healthy controls. EEGs analyzed with the SPR method together with clinical data recorded at baseline were evaluated. The patients were followed up for a mean of 62.5 (SD 17.6) months and reexamined. RESULTS: Of 200 participants with valid clinical information, 70 had converted to dementia, and 52 had developed Alzheimer's disease. Receiver-operating characteristic analysis of the EEG results as defined by a dementia index (DI) ranging from 0 to 100 revealed that the area under the curve was 0.78 (95% CI 0.70-0.85), corresponding to a sensitivity of 71%, specificity of 69%, and accuracy of 69%. A logistic regression analysis showed that by adding results of a cognitive test at baseline to the EEG DI, accuracy could improve. CONCLUSION: We conclude that applying qEEG using the automated SPR method can be helpful in identifying patients with SCD and MCI that have a high risk of converting to dementia over a 5-year period. As the discriminant power of the method is of moderate degree, it should be used in addition to routine diagnostic methods.

Does hyperglycemia downregulate glucose transporters in the brain?

Diabetes is a metabolic condition associated with hyperglycemia manifested by the elevation of blood glucose levels occurring when the pancreas decreases or stops the production of insulin, in case of insulin resistance or both. The current literature supports that insulin resistance may be responsible for the memory decline associated with diabetes. Glucose transporters (GLUTs) are a family of proteins involved in glucose transport across biological membranes. GLUT-1 and GLUT-3 are involved in glucose delivery to the brain. Evidence suggests that both transporters are downregulated in chronic peripheral hyperglycemia. Here we show the mechanisms of glucose transport and its influence on cognitive function, including a hypothesis of how peripheral hyperglycemia related genes network interactions may lead to glucose transporters downregulation and its possible consequences.

Applicability of the locus of control of behaviour scale for people with dementia.

OBJECTIVE: To investigate the applicability of the Locus of Control of Behaviour scale (LoCB) for people with dementia. METHOD: A sample of 534 participants with dementia (78.4 mean age, 58% female) were included. Assessment included the LoCB, the Montgomery-Aasberg Depression Rating Scale (MADRS), the Mini-Mental Status Examination Norwegian revised (MMSE-NR) and the Instrumental Activities of Daily Living (I-ADL). Completion percentages and internal reliability of LoCB were examined for predefined MMSE-NR groups (0-4, 5-9, 10-14, 15-19, 20-24, 25-27, and 28-30). Factors associated with completion were analysed, and a principal component analysis (PCA) of the LoCB was performed. Sum score and component subscale scores were compared to MADRS and MMSE-NR scores. RESULTS: In total, 234 participants completed the LoCB. Completion percentages ranged from 74% (MMSE-NR 28-30) to 0% (MMSE-NR 0-9). Internal reliability was between 0.80 and 0.72 in groups with MMSE-NR > 9, except in MMSE-NR 20-24 (0.52). Age, MMSE-NR and education were associated with completion. The PCA yielded three components - powerful others, internal, and luck/fate - with explained variance of 41.3%. Participants with MADRS > 7 scored higher on the LoCB sum score, powerful others and internal subscale scores. No difference was found regarding the luck/fate subscale score. MMSE-NR did not affect LoCB scores. CONCLUSION: Older age, less education, and more cognitive impairment decreased the likelihood of completion. However, psychometric test results indicate that those who completed the LoCB understood the questions, even with severe cognitive impairment. We conclude, therefore, that the LoCB is applicable for investigating control orientation among people with dementia.

The course of depressive symptoms with decline in cognitive function - a longitudinal study of older adults receiving in-home care at baseline.

BACKGROUND: Depressive symptoms in old age are common, but the prevalence, persistence, and incidence of depressive symptoms in older adults with and without dementia receiving in-home care is less well studied, and descriptions of the relationship between severity of cognitive decline and depressive symptoms over time is, to our knowledge, lacking. The aim of the present study was to describe the prevalence, incidence and persistence of depressive symptoms over a 36-month follow-up period among older adults receiving in-home care at baseline, and to explore the association between cognitive function and the course of depressive symptoms over time. METHODS: In all, 1001 older people (≥ 70 years) receiving in-home care were included in a longitudinal study with three assessments over 36 months. Depressive symptoms were assessed using the Cornell Scale for Depression in Dementia. Clinical Dementia Rating Scale, diagnosis of dementia and mild cognitive impairment, general medical health, personal and instrumental activities of daily living, neuropsychiatric symptoms and the use of psychotropic medication were evaluated during the three assessments. Baseline demographic characteristics and information on nursing home residency at follow-up were recorded. Linear mixed models were estimated. RESULTS: The baseline prevalence and cumulative incidence of single depressive symptoms were higher in those with dementia at baseline than in those without dementia. The persistence of depressive symptoms did not differ between those with or without dementia at baseline. The severity of cognitive impairment and mean depressive symptom score assessed simultaneously were positively associated, but the strength of the association changed over time and was not significant at the last assessment. Furthermore, being younger, female, in very poor physical health, with neuropsychiatric symptoms and not becoming a nursing home resident were associated with more depressive symptoms when assessed simultaneously. CONCLUSION: The baseline prevalence and cumulative incidence of depressive symptoms in those with and without dementia at baseline, as well as the relationship we found between the degree of cognitive decline and depressive symptoms over time show that depression and dementia are interconnected. Nurses and clinicians should pay attention to cognitive status when observing or evaluating depression among older adults receiving in-home care.

Resilience in Carers of People With Young-Onset Alzheimer Disease.

Young-onset Alzheimer disease (YOAD) causes psychological and emotional difficulties for carers. However, even in the face of considerable caregiving demands and burden, some carers are resistant to stress, which may be a sign of resilience. This study investigated whether the clinical symptoms of the person with YOAD might be associated with resilience in their carers. A consecutive series of 43 persons with YOAD and their 43 family caregivers were assessed. The carers showed moderate to high level of resilience, low level of anxiety and depressive symptoms, and moderate level of burden. No relationship was found between resilience and sociodemographic characteristics of both carers and care recipient and with clinical characteristics of persons with YOAD. A linear regression analysis showed that resilience was inversely associated with carers' depressive symptoms. The findings suggest that resilience may mainly be related to carers' mental health.

Cortisol levels among older people with and without depression and dementia.

Cortisol dysregulation has been reported in dementia and depression. Cortisol levels and its associates were investigated among older people living at home and in nursing homes, in a cross-sectional study. A sample of 650 older people, from the community (home and nursing homes) and specialized care (memory clinics and old age psychiatry wards), mean age 76.8 (SD = 10.3) (dementia n = 319, depression, n = 154, dementia plus depression n = 53, and reference group n = 124), was included. Assessment included the Mini Mental State Examination (MMSE), Cornell scale for depression in dementia, activities of daily living scales, and salivary cortisol. Number of drugs was registered. The results showed that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. Characteristics significantly associated with cortisol levels were higher MMSE score (in patients with dementia and co-morbid depression), male gender (in people with dementia), and number of medications (in the reference group). We conclude that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. The association of cortisol level with MMSE score among patients with dementia and depression could further indicate that increased stress is related to cognitive function.

Association between vascular comorbidity and progression of Alzheimer's disease: a two-year observational study in Norwegian memory clinics.

BACKGROUND: Vascular risk factors increase the risk of Alzheimer's disease (AD), but there is limited evidence on whether comorbid vascular conditions and risk factors have an impact on disease progression. The aim of this study was to examine the association between vascular disease and vascular risk factors and progression of AD. METHODS: In a longitudinal observational study in three Norwegian memory clinics, 282 AD patients (mean age 73.3 years, 54% female) were followed for mean 24 (16-37) months. Vascular risk factors and vascular diseases were registered at baseline, and the vascular burden was estimated by the Framingham Stroke Risk Profile (FSRP). Cerebral medical resonance images (MRIs) were assessed for white matter hyperintensities (WMH), lacunar and cortical infarcts. The associations between vascular comorbidity and progression of dementia as measured by annual change in Clinical Dementia Rating Sum of Boxes (CDR-SB) scores were analysed by multiple regression analyses, adjusted for age and sex. RESULTS: Hypertension occurred in 83%, hypercholesterolemia in 53%, diabetes in 9%, 41% were overweight, and 10% were smokers. One third had a history of vascular disease; 16% had heart disease and 15% had experienced a cerebrovascular event. MRI showed lacunar infarcts in 16%, WMH with Fazekas score 2 in 26%, and Fazekas score 3 in 33%. Neither the vascular risk factors and diseases, the FSRP score, nor cerebrovascular disease was associated with disease progression in AD. CONCLUSIONS: Although vascular risk factors and vascular diseases were prevalent, no impact on the progression of AD after 2 years was shown.

Comparison of automated volumetry of the hippocampus using NeuroQuant® and visual assessment of the medial temporal lobe in Alzheimer's disease.

Background Different clinically feasible methods for evaluation of medial temporal lobe atrophy exists and are useful in diagnostic work-up of Alzheimer's disease (AD). Purpose To compare the diagnostic properties of two clinically available magnetic resonance imaging (MRI)-based methods-an automated volumetric software, NeuroQuant® (NQ) (evaluation of hippocampus volume) and the Scheltens scale (visual evaluation of medial temporal lobe atrophy [MTA])-in patients with AD dementia, and subjective and mild cognitive impairment (non-dementia). Material and Methods MRIs from 56 patients (31 AD, 25 non-dementia) were assessed with both methods. Correlations between the methods were calculated and receiver operating curve (ROC) analyses that yield area under the curve (AUC) statistics were conducted. Results High correlations were found between the two MRI assessments for the total hippocampal volume measured with NQ and mean MTA score (-0.753, P < 0.001), for the right (-0.767, P < 0.001), and for the left (-0.675, P < 0.001) sides. The NQ total measure yielded somewhat higher AUC (0.88, "good") compared to the MTA mean measure (0.80, "good") in the comparison of patients with AD and non-dementia, but the accuracy was in favor of the MTA scale. Conclusion The two methods correlated highly and both methods reached equally "good" power.

Progression of Alzheimer's Disease: A Longitudinal Study in Norwegian Memory Clinics.

BACKGROUND: The course of Alzheimer's disease (AD) varies considerably between individuals. There is limited evidence on factors important for disease progression. OBJECTIVE: The primary aim was to study the progression of AD, as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). Secondary aims were to investigate whether baseline characteristics are important for differences in progression, and to examine the correlation between progression assessed using three different instruments: CDR-SB (0-18), the cognitive test Mini-Mental State Examination (MMSE, 0-30), and the functional measure Instrumental Activities of Daily Living (IADL, 0-1). METHODS: The Progression of AD and Resource use (PADR) study is a longitudinal observational study in three Norwegian memory clinics. RESULTS: In total, 282 AD patients (mean age 73.3 years, 54% female) were followed for mean 24 (16-37) months. The mean annual increase in CDR-SB was 1.6 (SD 1.8), the mean decrease in MMSE score 1.9 (SD 2.6), and the mean decrease in IADL score 0.13 (SD 0.14). Of the 282 patients, 132 (46.8%) progressed slowly, with less than 1 point yearly increase in CDR-SB. Cognitive test results at baseline predicted progression rate, and together with age, ApoE, history of hypertension, and drug use could explain 17% of the variance in progression rate. The strongest correlation of change was found between CDR-SB and IADL scores, the weakest between MMSE and IADL scores. CONCLUSION: Progression rate varied considerably among AD patients; about half of the patients progressed slowly. Cognitive test results at baseline were predictors of progression rate.

MRI-assessed atrophy subtypes in Alzheimer's disease and the cognitive reserve hypothesis.

BACKGROUND/AIMS: MRI assessment of the brain has demonstrated four different patterns of atrophy in patients with Alzheimer's disease dementia (AD): typical AD, limbic-predominant AD, hippocampal-sparing AD, and a subtype with minimal atrophy, previously referred to as no-atrophy AD. The aim of the present study was to identify and describe the differences between these four AD subtypes in a longitudinal memory-clinic study. METHODS: The medial temporal lobes, the frontal regions, and the posterior regions were assessed with MRI visual rating scales to categorize 123 patients with mild AD according to ICD-10 and NINCDS-ADRDA criteria and the clinical dementia rating scale (CDR) into atrophy subtypes. Demographic data, neuropsychological measures, cerebrospinal-fluid biomarkers, and progression rate of dementia at two-year follow-up were compared between the groups. RESULTS: Typical AD was found in 59 patients (48%); 29 (24%) patients had limbic-predominant AD; 19 (15%) had hippocampal-sparing AD; and 16 (13%) belonged to the group with minimal atrophy. No differences were found regarding cognitive test results or progression rates between the different subtypes. Using adjusted logistic regression analysis, we found that the patients in the minimal-atrophy group were less educated, had a lower baseline CDR sum of boxes score, and had higher levels of amyloid ß in the cerebrospinal fluid. CONCLUSION: Previous results concerning the prevalence and the similar phenotypic expressions of the four AD subtypes were confirmed. The main finding was that patients with minimal atrophy as assessed by MRI had less education than the other AD subtypes and that this could support the cognitive reserve hypothesis and, at least in part, explain the lower degree of atrophy in this group. Patients with less formal education might present with clinically typical AD symptoms before they have positive biomarkers of AD and this finding might challenge suggested biomarker-based criteria for AD.

Distinguishing early and late brain aging from the Alzheimer's disease spectrum: consistent morphological patterns across independent samples.

Alzheimer's disease (AD) is a debilitating age-related neurodegenerative disorder. Accurate identification of individuals at risk is complicated as AD shares cognitive and brain features with aging. We applied linked independent component analysis (LICA) on three complementary measures of gray matter structure: cortical thickness, area and gray matter density of 137 AD, 78 mild (MCI) and 38 subjective cognitive impairment patients, and 355 healthy adults aged 18-78 years to identify dissociable multivariate morphological patterns sensitive to age and diagnosis. Using the lasso classifier, we performed group classification and prediction of cognition and age at different age ranges to assess the sensitivity and diagnostic accuracy of the LICA patterns in relation to AD, as well as early and late healthy aging. Three components showed high sensitivity to the diagnosis and cognitive status of AD, with different relationships with age: one reflected an anterior-posterior gradient in thickness and gray matter density and was uniquely related to diagnosis, whereas the other two, reflecting widespread cortical thickness and medial temporal lobe volume, respectively, also correlated significantly with age. Repeating the LICA decomposition and between-subject analysis on ADNI data, including 186 AD, 395 MCI and 220 age-matched healthy controls, revealed largely consistent brain patterns and clinical associations across samples. Classification results showed that multivariate LICA-derived brain characteristics could be used to predict AD and age with high accuracy (area under ROC curve up to 0.93 for classification of AD from controls). Comparison between classifiers based on feature ranking and feature selection suggests both common and unique feature sets implicated in AD and aging, and provides evidence of distinct age-related differences in early compared to late aging.

Trajectories of depressive symptoms and their relationship to the progression of dementia.

BACKGROUND: The relationship between progression of Alzheimer's disease and depression and its underlying mechanisms has scarcely been studied. METHODS: A sample of 282 outpatients with Alzheimer's disease (AD; 105 with amnestic AD and 177 with Alzheimer's dementia) from Norway were followed up for an average of two years. Assessment included Cornell Scale for Depression in Dementia and Clinical Dementia Rating Scale (CDR) at baseline and follow-up to examine the relationship between AD and depression. Additionally, MRI of the brain, CSF dementia biomarkers and APOE status were assessed at baseline. Progression of dementia was defined as the difference between CDR sum of boxes at follow-up and baseline (CDR-SB change). Trajectories of depressive symptoms on the Cornell Scale were identified using growth mixture modeling. Differences between the trajectories in regard to patients' characteristics were investigated. RESULTS: Three distinct trajectories of depressive symptoms were identified: 231 (82.8%) of the patients had stable low-average scores on the Cornell Scale (Class 1); 11 (3.9%) had high and decreasing scores (Class 2); and 37 (13.3%) had moderate and increasing scores (Class 3). All classes had average probabilities over 80%, and confidence intervals were non-overlapping. The only significant characteristic associated with membership in class 3 was CDR-SB change. LIMITATIONS: Not all patients screened for participation were included in the study, but the included and non-included patients did not differ significantly. Some patients with amnestic MCI might have been misdiagnosed. CONCLUSION: A more rapid progression of dementia was found in a group of patients with increasing depressive symptoms.

Visual Evaluation of Medial Temporal Lobe Atrophy as a Clinical Marker of Conversion from Mild Cognitive Impairment to Dementia and for Predicting Progression in Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease.

BACKGROUND/AIMS: To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). METHODS: vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria. Demographic data, the Consortium to Establish a Registry for Alzheimer's Disease 10-word delayed recall, APOE ɛ4 status, Cornell Scale for Depression in Dementia, and comorbid hypertension were used as covariates. RESULTS: vaMTA was associated with MCI conversion in an unadjusted model but not in an adjusted model (p = 0.075), where delayed recall and APOE ɛ4 status were significant predictors. With CDR-SB change as the outcome, an interaction between vaMTA and diagnosis was found, but in the adjusted model only delayed recall and age were significant predictors. For vaMTA below 2, the association between vaMTA and CDR-SB change differed between diagnostic groups. Similar results were found based on a trajectory analysis. CONCLUSION: In adjusted models, memory function, APOE ɛ4 status and age were significant predictors of disease progression, not vaMTA. The association between vaMTA and CDR-SB change was different in patients with MCI and Alzheimer's disease dementia.