A Systematic Review of Subjective Cognitive Characteristics Predictive of Longitudinal Outcomes in Older Adults.

BACKGROUND AND OBJECTIVES: Subjective cognitive decline (SCD) is a common experience of self-perceived decline without objective cognitive impairment among older adults. SCD has been conceptualized as very early Alzheimer's disease (AD), but the specific SCD features predictive of clinical or cognitive decline remain unclear. This systematic review is the first to characterize specific SCD features and their relation to longitudinal outcomes. RESEARCH DESIGN AND METHODS: Multiple electronic databases were searched from inception until August 2021 for longitudinal studies of adults aged ≥50 (mean ≥60) and free of dementia, with baseline SCD measurement and clinical or cognitive follow-up. Studies were screened for inclusion criteria and assessed for risk of bias using weight-of-evidence ratings. RESULTS: Five hundred and seventy potentially relevant studies were identified, and 52 studies were evaluated for eligibility after initial screening. Thirty-three studies with medium to high weight-of-evidence ratings were included, and results were narratively synthesized. Measurement methods varied substantially across studies: the majority (n = 27) assessed SCD symptom types and intensity, and consistently reported that a higher symptom burden increased the risk for mild cognitive impairment (MCI) and dementia. The evidence was less compelling for cognitive outcomes. A handful of studies (n = 5) suggested a predictive role for SCD symptom consistency and informant corroboration. DISCUSSION AND IMPLICATIONS: SCD symptom intensity emerged from our review as the most reliable predictor of future clinical outcomes. Combinations of SCD-Plus symptoms also had predictive utility. No single symptom was uniquely prognostic. Our findings support the quantitative evaluation of SCD symptoms in the assessment of risk for progression to MCI or dementia.

Brain Imaging Abnormalities in Mixed Alzheimer's and Subcortical Vascular Dementia.

BACKGROUND: A large proportion of Alzheimer's disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity. OBJECTIVE: To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD. METHODS: We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures. RESULTS: Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD). CONCLUSION: These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function.

BACKGROUND: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms. METHODS: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up). DISCUSSION: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.

Older Adults' Likelihood of Participating in Home-Based Cognitive Assessment.

INTRODUCTION: Timely detection of cognitive impairment among older adults has shown to lead to better health and financial outcomes but is hampered by psychological, financial, and physical barriers to participation in cognitive assessment. Home-based cognitive assessment (HBCA) could help overcome some of these barriers. This study aimed to examine older adults' likelihood of participation in HBCA and identify factors predicting this likelihood. MATERIALS AND METHODS: A cross-sectional online survey distributed through Amazon Mechanical Turk, was used to collect data from adults aged 50 years or older residing in the USA The survey was designed to gauge attitudes toward technology and cognitive assessment and to measure psychological variables including subjective cognitive decline (SCD), depression, and anxiety. Information on income and geographic location (rural vs. suburban and urban) was also collected. Univariate and hierarchical regression analyses were conducted to examine the contributions of these variables to a composite measure of likelihood of participation in HBCA. RESULTS: Complete data were obtained on n = 483 (age 50-79). Approximately, two-thirds of respondents described themselves as likely or very likely to participate in HBCA. In univariate analyses, younger age, higher income, higher technology assessment acceptance scores, and higher SCD burden were associated with higher likelihood of participation. Hierarchical regression revealed significant stepwise increments in explained variance: demographic variables 4.1%, technology acceptance 25.2%, assessment acceptance 15.4%, and SCD burden 1.6%. The contribution of SCD was moderated by sex and found for women but not for men. DISCUSSION/CONCLUSION: A large proportion of adults aged 50 and above described themselves likely to participate in HBCA. Middle-aged, technology-savvy, higher income adults expressed the most positive attitudes toward this type of service. Of interest is that HBCA may be particularly acceptable among older women with SCD, a group known to be at risk of cognitive decline. Our findings support the expansion of cognitive assessment services to the home setting.

FDG-PET in presymptomatic C9orf72 mutation carriers.

OBJECTIVE: Our aim is to investigate patterns of brain glucose metabolism using fluorodeoxyglucose positron emission tomography (FDG-PET) in presymptomatic carriers of the C9orf72 repeat expansion to better understand the early preclinical stages of frontotemporal dementia (FTD). METHODS: Structural MRI and FDG-PET were performed on clinically asymptomatic members of families with FTD caused by the C9orf72 repeat expansion (15 presymptomatic mutation carriers, C9orf72+; 20 non-carriers, C9orf72-). Regional glucose metabolism in cerebral and cerebellar gray matter was compared between groups. RESULTS: The mean age of the C9orf72+ and C9orf72- groups were 45.3 ± 10.6 and 56.0 ± 11.0 years respectively, and the mean age of FTD onset in their families was 56 ± 7 years. Compared to non-carrier controls, the C9orf72+ group exhibited regional hypometabolism, primarily involving the cingulate gyrus, frontal and temporal neocortices (left > right) and bilateral thalami. CONCLUSIONS: The C9orf72 repeat expansion is associated with changes in brain glucose metabolism that are demonstrable up to 10 years prior to symptom onset and before changes in gray matter volume become significant. These findings indicate that FDG-PET may be a particularly sensitive and useful method for investigating and monitoring the earliest stages of FTD in individuals with this underlying genetic basis.

Distance Assessment for Detecting Cognitive Impairment in Older Adults: A Systematic Review of Psychometric Evidence.

INTRODUCTION: Distance or remote cognitive assessments, administered via phone or computer platforms, have emerged as possible alternatives to traditional assessments performed during office visits. Distance refers to any nontraditional assessment feature, not only or necessarily location. We conducted a systematic review to examine the psychometric soundness of these approaches. METHOD: We searched PubMed, PsycINFO, AgeLine, and Academic Search Premier for articles published between January 2008 and June 2020. Studies were included if participants were over the age of 50, a structured assessment of cognitive function in older adults was evaluated, the assessment method was deemed distant, and validity and/or reliability data were reported. Assessment distance was defined as having any of the following features: use of an electronic test interface, nonroutine test location (e.g., home), test self-administered, and test unsupervised. Distance was categorized as low, intermediate, or high. RESULTS/DISCUSSION: Twenty-six studies met inclusion criteria. Sample sizes ranged from n = 8 to 8,627, and the mean age ranged from 57 to 83. Assessments included screens, brief or full batteries, and were performed via videoconferencing, phone, smartphone, or tablet/computer. Ten studies reported on low distance, 11 on intermediate distance, and 5 studies for high distance assessments. Invalid performance data were observed with older age and cognitive impairment. Convergent validity data were reported consistently and suggested a decline with increasing distance: r = 0.52-0.80 for low, 0.49-0.75 for intermediate, and 0.41-0.53 for high distance. Diagnostic validity estimates presented a similar pattern. Reliability data were reported too inconsistently to allow evaluation. CONCLUSION: The validity of cognitive assessments with older adults appears supported at lower but not higher distance. Less is known about the reliability of such assessments. Future research should delineate the person and procedure boundaries for valid and reliable test results.

Older Adults With Subjective Cognitive Decline Worry About the Emotional Impact of Cognitive Test Results.

INTRODUCTION: Older adults with subjective cognitive decline (SCD) would benefit from routine cognitive testing as they are twice as likely to develop dementia. Worries about concerning test results may diminish participation. The current study aimed to characterize the pattern of worries among older adults with and without SCD. METHODS: Adults 50 years or above completed the Attitudes Around Cognitive Testing questionnaire on Mechanical Turk.com or in a primary care setting. Mechanical Turk.com is an online crowdsourcing site where requesters (eg, researchers) post jobs (eg, surveys or tasks) and workers (eg, respondents) choose which jobs to do for pay. Respondents were asked about perceived cognitive decline and about different types of worries they anticipated having if they received concerning test results. RESULTS: We report data for 393 respondents (online: n=296, primary care: n=97), mean age of 63 years, age range of 50 to 91 years, and 60% endorsing SCD. Compared with No SCD, those with SCD anticipated a higher number of worries centered disproportionately on worries of becoming depressed, ashamed or embarrassed, feeling "stupid" and unable to do things, and being put in a nursing home. We observed this SCD pattern of worries in both samples. DISCUSSION: Individuals with SCD worry about the emotional consequences of cognitive testing. This at-risk group would benefit from interventions focused on these concerns to increase patient engagement with cognitive tests.

Predementia Brain Changes in Progranulin Mutation: A Systematic Review of Neuroimaging Evidence.

BACKGROUND: Mutations in the progranulin (GRN) gene are a major cause of familial frontotemporal dementia. They result in a loss of progranulin levels and in GRN-related brain degenerative changes that unfold over years if not decades. The aim of our review was to summarize the evidence on emerging functional and structural brain abnormalities in carriers of GRN mutations. SUMMARY: We performed a systematic search for studies that used at least one modality (structural MRI, fMRI, fluorodeoxyglucose positron emission tomography, diffusion tensor imaging) to compare mutation carriers to non-carrier controls. Our search produced 13 studies published between 2008 and 2017, the majority cross-sectional, with carrier sample sizes ranging from 5 to 65. Key Messages: The aggregate findings suggest that (1) measurable brain changes are detectable in at least some mutation carriers 20-25 years prior to disease onset; (2) functional/metabolic changes progress more consistently over time than structural changes; (3) the topographic pattern is anterior to posterior, not always asymmetric, and maps onto known functional networks.

Neuropsychological Performance Patterns of Adult ADHD Subtypes.

Objective: Neuropsychological performance patterns associated with adult ADHD subtypes are unknown. The aim of the current systematic review was to identify and synthesize available literature regarding neuropsychological performance associated with adult ADHD subtypes. Method: Searches were completed using the databases PsycINFO and PubMed for studies published before March 2017 addressing adult ADHD subtypes and neuropsychological performance. Data characterizing the neuropsychological tests utilized in each study were obtained and sorted into eight domains. To summarize the results of all comparisons (ADHD subtype compared with control, or to each other), we counted the proportion of tests within each domain with significant group differences. Results/Conclusion: We deemed four domains informative in differentiating ADHD subtypes from controls. Of these, memory was the only domain that held promise in distinguishing ADHD-Inattentive and ADHD-Combined. Limitations of the available literature are highlighted and recommendations for future research are provided.

The Impact of Covert Lacunar Infarcts and White Matter Hyperintensities on Cognitive and Motor Outcomes After Stroke.

BACKGROUND AND AIMS: In addition to overt stroke lesions, co-occurring covert lesions, including white matter hyperintensities (WMH) and covert lacunar infarcts (CLI), contribute to poststroke outcome. The purpose of this study was to examine the relationship between covert lesions, and motor and cognitive outcomes in individuals with chronic stroke. METHODS: Volumetric quantification of clinically overt strokes, covert lesions (periventricular and deep: pWMH, dWMH, pCLI, dCLI), ventricular and sulcal CSF (vCSF, sCSF), and normal appearing white (NAWM) and gray matter (NAGM) was performed using structural magnetic resonance imaging. We assessed motor impairment and function, and global cognition, memory, and other cognitive domains. When correlation analysis identified more than one MR parameter relating to stroke outcomes, we used regression modeling to identify which factor had the strongest impact. RESULTS: Neuropsychological and brain imaging data were collected from 30 participants at least 6 months following a clinically diagnosed stroke. Memory performance related to vCSF (r = -0.52, P = .004). The strongest predictor of nonmemory domains was pCLI (r2 = 0.28, P = .004). Motor impairment and function were most strongly predicted by the volume of stroke and NAWM (r2 = 0.36; P = .001), and dWMH (r2 = 0.39; P = .001) respectively. CONCLUSIONS: Covert lesion type and location have important consequences for post-stroke cognitive and motor outcome. Limiting the progression of covert lesions in aging populations may enhance the degree of recovery post-stroke.

Quantitative assessment of field strength, total intracranial volume, sex, and age effects on the goodness of harmonization for volumetric analysis on the ADNI database.

When analyzing large multicenter databases, the effects of multiple confounding covariates increase the variability in the data and may reduce the ability to detect changes due to the actual effect of interest, for example, changes due to disease. Efficient ways to evaluate the effect of covariates toward the data harmonization are therefore important. In this article, we showcase techniques to assess the "goodness of harmonization" of covariates. We analyze 7,656 MR images in the multisite, multiscanner Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We present a comparison of three methods for estimating total intracranial volume to assess their robustness and correct the brain structure volumes using the residual method and the proportional (normalization by division) method. We then evaluated the distribution of brain structure volumes over the entire ADNI database before and after accounting for multiple covariates such as total intracranial volume, scanner field strength, sex, and age using two techniques: (a) Zscapes, a panoramic visualization technique to analyze the entire database and (b) empirical cumulative distributions functions. The results from this study highlight the importance of assessing the goodness of data harmonization as a necessary preprocessing step when pooling large data set with multiple covariates, prior to further statistical data analysis.

Older Adults' Attitudes towards Cognitive Testing: Moving towards Person-Centeredness.

BACKGROUND: Research on person-centered cognitive testing is beginning to emerge. The current study is the first to focus on eliciting concrete preferences around the test experience. METHODS: Adults ≥50 years old completed the Attitudes Around Cognitive Testing (AACT) questionnaire on mturk.com. AACT elicits preferences for cognitive tests, the importance attributed to having choices, and willingness to engage in testing. RESULTS: Data are reported for 289 respondents. The proportion of participants expressing preferences varied by domain (modality [49.5%], location [47.2%], company [80.1%], result delivery [78.3-89.7%]). Importance ratings for all domains had a median of 4 and a range of 1-5 using a Likert scale of agreement. Most participants (85.5%) were willing to engage in testing. CONCLUSION: Older adults have preferences for cognitive tests, especially with delivery of results.

Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers.

Frontotemporal dementia (FTD) is a neurodegenerative disease with a strong genetic basis. Understanding the structural brain changes during pre-symptomatic stages may allow for earlier diagnosis of patients suffering from FTD; therefore, we investigated asymptomatic members of FTD families with mutations in C9orf72 and granulin (GRN) genes. Clinically asymptomatic subjects from families with C9orf72 mutation (15 mutation carriers, C9orf72+; and 23 non-carriers, C9orf72-) and GRN mutations (9 mutation carriers, GRN+; and 15 non-carriers, GRN-) underwent structural neuroimaging (MRI). Cortical thickness and subcortical gray matter volumes were calculated using FreeSurfer. Group differences were evaluated, correcting for age, sex and years to mean age of disease onset within the subject's family. Mean age of C9orf72+ and C9orf72- were 42.6 ±â€¯11.3 and 49.7 ±â€¯15.5 years, respectively; while GRN+ and GRN- groups were 50.1 ±â€¯8.7 and 53.2 ±â€¯11.2 years respectively. The C9orf72+ group exhibited cortical thinning in the temporal, parietal and frontal regions, as well as reduced volumes of bilateral thalamus and left caudate compared to the entire group of mutation non-carriers (NC: C9orf72- and GRN- combined). In contrast, the GRN+ group did not show any significant differences compared to NC. C9orf72 mutation carriers demonstrate a pattern of reduced gray matter on MRI prior to symptom onset compared to GRN mutation carriers. These findings suggest that the preclinical course of FTD differs depending on the genetic basis and that the choice of neuroimaging biomarkers for FTD may need to take into account the specific genes involved in causing the disease.

Decreased Prefrontal Activation during Matrix Reasoning in Predementia Progranulin Mutation Carriers.

We tested the potential of task-based functional neuroimaging as a biomarker of emerging prefrontal brain changes in progranulin (GRN) mutations carriers. Five GRN mutation carriers free of frontotemporal dementia (FTD) and 11 non-carriers from families with FTD-GRN underwent functional MRI while solving matrix-reasoning problems. Mutation carriers displayed slower responses for more difficult problems and lower lateral prefrontal activation across all problems. Overall task-evoked posterior ventrolateral prefrontal activation predicted mutation status with 100% sensitivity and 91% specificity. Volumetric differences did not account for activation differences. Prefrontal activation may have utility as a biomarker in GRN mutation.

Sex Difference in Aerobic Exercise Efficacy to Improve Cognition in Older Adults with Vascular Cognitive Impairment: Secondary Analysis of a Randomized Controlled Trial.

Aerobic training (AT) is a promising, non-pharmacological intervention to mitigate the deleterious effects of aging and disease on brain health. However, a large amount of variation exists in its efficacy. This is a secondary analysis of a randomized controlled trial of AT in 71 older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Specifically, we investigated: 1) whether sex moderates the relationship between AT and executive functions, and 2) the role of brain derived neurotrophic factor (BDNF) and gains in functional fitness capacity. Older adults were randomly assigned to either 6-month, thrice-weekly AT or to usual care plus education (CON). At baseline, trial completion, and 6-month follow-up, executive functions were assessed with the Trail Making Test (A & B), verbal digits forward and backward test, and the Stroop Test. Functional fitness capacity was assessed with the 6-Minute Walk Test. Compared with CON, AT significantly improved Trail Making Test performance in females but not males, an effect that was retained at follow-up. AT significantly increased BDNF levels in females but decreased levels in males. On the other hand, AT led to significant gains in functional fitness capacity in males only. This study provides evidence that sex differences exist in AT efficacy on brain health as well as in the biological mechanisms subserving AT.

Associations between cerebral amyloid and changes in cognitive function and falls risk in subcortical ischemic vascular cognitive impairment.

BACKGROUND: To determine the association between amyloid-beta (Aß) plaque deposition and changes in global cognition, executive functions, information processing speed, and falls risk over a 12-month period in older adults with a primary clinical diagnosis of subcortical ischemic vascular cognitive impairment (SIVCI). METHODS: This is a secondary analysis of data acquired from a subset of participants (N = 22) who were enrolled in a randomized controlled trial of aerobic exercise (NCT01027858). The subset of individuals completed an 11C Pittsburgh compound B (PIB) scan. Cognitive function and falls risk were assessed at baseline, 6-months, and 12-months. Global cognition, executive functions, and information processing speed were measured using: 1) ADAS-Cog; 2) Trail Making Test; 3) Digit Span Test; 4) Stroop Test, and 5) Digit Symbol Substitution Test. Falls risk was measured using the Physiological Profile Assessment. Hierarchical multiple linear regression analyses determined the unique contribution of Aß on changes in cognitive function and falls risk at 12-months after controlling for experimental group (i.e. aerobic exercise training or usual care control) and baseline performance. To correct for multiple comparisons, we applied the Benjamini-Hochberg procedure to obtain a false discovery rate corrected threshold using alpha = 0.05. RESULTS: Higher PIB retention was significantly associated with greater decrements in set shifting (Trail Making Test, adjusted R2 = 35.3%, p = 0.002), attention and conflict resolution (Stroop Test, adjusted R2 = 33.4%, p = 0.01), and information processing speed (Digit Symbol Substitution Test, adjusted R2 = 24.4%, p = 0.001) over a 12-month period. Additionally, higher PIB retention was significantly associated with increased falls risk (Physiological Profile Assessment, adjusted R2 = 49.1%, p = 0.04). PIB retention was not significantly associated with change in ADAS-Cog and Verbal Digit Span Test (p > 0.05). CONCLUSIONS: Symptoms associated with SIVCI may be amplified by secondary Aß pathology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01027858 , December 7, 2009.

Economic evaluation of aerobic exercise training in older adults with vascular cognitive impairment: PROMoTE trial.

BACKGROUND/OBJECTIVES: Evidence suggests that aerobic exercise may slow the progression of subcortical ischaemic vascular cognitive impairment (SIVCI) by modifying cardiovascular risk factors. Yet the economic consequences relating to aerobic training (AT) remain unknown. Therefore, our primary objective was to estimate the incremental cost per quality-adjusted life years (QALYs) gained of a thrice weekly AT intervention compared with usual care. DESIGN: Cost-utility analysis alongside a randomised trial. SETTING: Vancouver, British Columbia, Canada. PARTICIPANTS: 70 adults (mean age of 74 years, 51% women) who meet the diagnostic criteria for mild SIVCI. INTERVENTION: A 6-month, thrice weekly, progressive aerobic exercise training programme compared with usual care (CON; comparator) with a follow-up assessment 6 months after formal cessation of aerobic exercise training. MEASUREMENTS: Healthcare resource usage was estimated over the 6-month intervention and 6-month follow-up period. Health status (using the EQ-5D-3L) at baseline and trial completion and 6-month follow-up was used to calculate QALYs. The incremental cost-utility ratio (cost per QALY gained) was calculated. RESULTS: QALYs were both modestly greater, indicating a health gain. Total healthcare costs (ie, 1791±1369 {2015 $CAD} at 6 months) were greater, indicating a greater cost for the thrice weekly AT group compared with CON. From the Canadian healthcare system perspective, the incremental cost-utility ratios for thrice weekly AT were cost-effective compared with CON, when using a willingness to pay threshold of $CAD 20 000 per QALY gained or higher. CONCLUSIONS: AT represents an attractive and potentially cost-effective strategy for older adults with mild SIVCI. TRIAL REGISTRATION NUMBER: NCT01027858.

The 2002 NIMH Provisional Diagnostic Criteria for Depression of Alzheimer's Disease (PDC-dAD): Gauging their Validity over a Decade Later.

Presented herein is evidence for criterion, content, and convergent/discriminant validity of the NIMH-Provisional Diagnostic Criteria for depression of Alzheimer's Disease (PDC-dAD) that were formulated to address depression in Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we examined criterion validity evidence in epidemiological and clinical studies comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and International Classification of Disease (ICD 9) depression diagnostic criteria. We estimated prevalence of depression by PDC, DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic agreement between PDC and DSM. To gauge content validity, we reviewed rates of symptom endorsement for each diagnostic approach. Finally, we examined the PDC's relationship with assessment scales (global cognition, neuropsychiatric, and depression definition) for convergent validity evidence. The aggregate evidence supports the validity of the PDC-dAD. Our findings suggest that depression in AD differs from other depressive disorders including Major Depressive Disorder (MDD) in that dAD is more prevalent, with generally a milder presentation and with unique features not captured by the DSM. Although the PDC are the current standard for diagnosis of depression in AD, we identified the need for their further optimization based on predictive validity evidence.

Aerobic exercise and vascular cognitive impairment: A randomized controlled trial.

OBJECTIVE: To assess the efficacy of a progressive aerobic exercise training program on cognitive and everyday function among adults with mild subcortical ischemic vascular cognitive impairment (SIVCI). METHODS: This was a proof-of-concept single-blind randomized controlled trial comparing a 6-month, thrice-weekly, progressive aerobic exercise training program (AT) with usual care plus education on cognitive and everyday function with a follow-up assessment 6 months after the formal cessation of aerobic exercise training. Primary outcomes assessed were general cognitive function (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog]), executive functions (Executive Interview [EXIT-25]), and activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]). RESULTS: Seventy adults randomized to aerobic exercise training or usual care were included in intention-to-treat analyses (mean age 74 years, 51% female, n = 35 per group). At the end of the intervention, the aerobic exercise training group had significantly improved ADAS-Cog performance compared with the usual care plus education group (-1.71 point difference, 95% confidence interval [CI] -3.15 to -0.26, p = 0.02); however, this difference was not significant at the 6-month follow-up (-0.63 point difference, 95% CI -2.34 to 1.07, p = 0.46). There were no significant between-group differences at intervention completion and at the 6-month follow-up in EXIT-25 or ADCS-ADL performance. Examination of secondary measures showed between-group differences at intervention completion favoring the AT group in 6-minute walk distance (30.35 meter difference, 95% CI 5.82 to 54.86, p = 0.02) and in diastolic blood pressure (-6.89 mm Hg difference, 95% CI -12.52 to -1.26, p = 0.02). CONCLUSIONS: This study provides preliminary evidence for the efficacy of 6 months of thrice-weekly progressive aerobic training in community-dwelling adults with mild SIVCI, relative to usual care plus education. CLINICALTRIALSGOV IDENTIFIER: NCT01027858. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for adults with mild SIVCI, an aerobic exercise program for 6 months results in a small, significant improvement in ADAS-Cog performance.