Cardiorespiratory Fitness and White Matter Integrity in Mild Cognitive Impairment

2018;61(2):729-739. doi: 10.3233/JAD-170415.

Cardiorespiratory Fitness and White Matter Neuronal Fiber Integrity in Mild Cognitive Impairment.

Ding K1, Tarumi T1,2, Zhu DC3, Tseng BY4,2, Thomas BP5, Turner M2, Repshas J2, Kerwin DR6, Womack KB1,7, Lu H5, Cullum CM1,7, Zhang R1,4,2.



Mounting evidence showed the self-reported levels of physical activity are positively associated with white matter (WM) integrity and cognitive performance in normal adults and patients with mild cognitive impairment (MCI). However, the objective measure of cardiorespiratory fitness (CRF) was not used in these studies.


To determine the associations of CRF measured by maximal oxygen uptake (VO2max) with WM fiber integrity and neurocognitive performance in older adults with MCI.


Eighty-one participants (age = 65±7 years, 43 women), including 26 cognitively normal older adults and 55 amnestic MCI patients, underwent VO2max test to measure CRF, diffusion tensor imaging (DTI) to assess WM fiber integrity, and neurocognitive assessment focused on memory and executive function. DTI data were analyzed by the tract-based spatial statistics and region-of-interest approach.


Cognitively normal older adults and MCI patients were not different in global WM fiber integrity and VO2max. VO2max was associated positively with DTI metrics of fractional anisotropy in ∼54% WM fiber tracts, and negatively with mean and radial diffusivities in ∼46% and ∼56% of the WM fiber tracts. The associations of VO2max with DTI metrics remained statistically significant after adjustment of age, sex, body mass index, WM lesion burden, and MCI status. The DTI metrics obtained from the area that correlated to VO2max were associated with executive function performance in MCI patients.


Higher levels of CRF are associated with better WM fiber integrity, which in turn is correlated with better executive function performance in MCI patients.


Copyright IOS Press


Contribution of Alcohol Use Disorders to the Burden of Dementia

2018 Feb 20. pii: S2468-2667(18)30022-7. doi: 10.1016/S2468-2667(18)30022-7. [Epub ahead of print]

Contribution of alcohol use disorders to the burden of dementia in France 2008-13: a nationwide retrospective cohort study.

Schwarzinger M1, Pollock BG2, Hasan OSM3, Dufouil C4, Rehm J5; QalyDays Study Group.



Dementia is a prevalent condition, affecting 5-7% of people aged 60 years and older, and a leading cause of disability in people aged 60 years and older globally. We aimed to examine the association between alcohol use disorders and dementia risk, with an emphasis on early-onset dementia (<65 years).


We analysed a nationwide retrospective cohort of all adult (≥20 years) patients admitted to hospital in metropolitan France between 2008 and 2013. The primary exposure was alcohol use disorders and the main outcome was dementia, both defined by International Classification of Diseases, tenth revision discharge diagnosis codes. Characteristics of early-onset dementia were studied among prevalent cases in 2008-13. Associations of alcohol use disorders and other risk factors with dementia onset were analysed in multivariate Cox models among patients admitted to hospital in 2011-13 with no record of dementia in 2008-10.


Of 31 624 156 adults discharged from French hospitals between 2008 and 2013, 1 109 343 were diagnosed with dementia and were included in the analyses. Of the 57 353 (5·2%) cases of early-onset dementia, most were either alcohol-related by definition (22 338 [38·9%]) or had an additional diagnosis of alcohol use disorders (10 115 [17·6%]).

Alcohol use disorders were the strongest modifiable risk factor for dementia onset, with an adjusted hazard ratio of 3·34 (95% CI 3·28-3·41) for women and 3·36 (3·31-3·41) for men. Alcohol use disorders remained associated with dementia onset for both sexes (adjusted hazard ratios >1·7) in sensitivity analyses on dementia case definition (including Alzheimer’s disease) or older study populations. Also, alcohol use disorders were significantly associated with all other risk factors for dementia onset (all p<0·0001).


Alcohol use disorders were a major risk factor for onset of all types of dementia, and especially early-onset dementia. Thus, screening for heavy drinking should be part of regular medical care, with intervention or treatment being offered when necessary. Additionally, other alcohol policies should be considered to reduce heavy drinking in the general population.


Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.All rights reserved.


Can Exercise Improve Cognitive Symptoms of Alzheimer’s Disease?

 2018 Jan 24. doi: 10.1111/jgs.15241. [Epub ahead of print]

Can Exercise Improve Cognitive Symptoms of Alzheimer’s Disease? A Meta-Analysis.

Panza GATaylor BAMacDonald HVJohnson BTZaleski ALLivingston JThompson PDPescatello LS.



To examine the effects of exercise training on cognitive function in individuals at risk of or diagnosed with Alzheimer’s disease (AD).




PubMed, Scopus,, and ProQuest were searched from inception until August 1, 2017.


Nineteen studies with 23 interventions including 1,145 subjects with a mean age of 77.0 ± 7.5 were included. Most subjects were at risk of AD because they had mild cognitive impairment (64%) or a parent diagnosed with AD (1%), and 35% presented with AD.


Controlled studies that included an exercise-only intervention and a nondiet, nonexercise control group and reported pre- and post-intervention cognitive function measurements.


Cognitive function before and after the intervention and features of the exercise intervention.


Exercise interventions were performed 3.4 ± 1.4 days per week at moderate intensity (3.7 ± 0.6 metabolic equivalents) for 45.2 ± 17.0 minutes per session for 18.6 ± 10.0 weeks and consisted primarily of aerobic exercise (65%). Overall, there was a modest favorable effect of exercise on cognitive function (d+ = 0.47, 95% confidence interval (CI) = 0.26-0.68). Within-group analyses revealed that exercise improved cognitive function (d+w = 0.20, 95% CI = 0.11-0.28), whereas cognitive function declined in the control group (d+w = -0.18, 95% CI = -0.36 to 0.00). Aerobic exercise had a moderate favorable effect on cognitive function (d+w = 0.65, 95% CI = 0.35-0.95), but other exercise types did not (d+w = 0.19, 95% CI = -0.06-0.43).


Our findings suggest that exercise training may delay the decline in cognitive function that occurs in individuals who are at risk of or have AD, with aerobic exercise possibly having the most favorable effect. Additional randomized controlled clinical trials that include objective measurements of cognitive function are needed to confirm our findings.


© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Effect of Aerobic Exercise on Hippocampal Volume in Humans

 2018 Feb 1;166:230-238. doi: 10.1016/j.neuroimage.2017.11.007. Epub 2017 Nov 4.

Effect of aerobic exercise on hippocampal volume in humans: A systematic review and meta-analysis.

Firth JStubbs BVancampfort DSchuch FLagopoulos JRosenbaum SWard PB.


Hippocampal volume increase in response to aerobic exercise has been consistently observed in animal models. However, the evidence from human studies is equivocal.

We undertook a systematic review to identify all controlled trials examining the effect of aerobic exercise on the hippocampal volumes in humans, and applied meta-analytic techniques to determine if aerobic exercise resulted in volumetric increases.

We also sought to establish how volumechanges differed in relation to unilateral measures of left/right hippocampal volume, and across the lifespan. A systematic search identified 4398 articles, of which 14 were eligible for inclusion in the primary analysis.

A random-effects meta-analysis showed no significant effect of aerobic exercise on total hippocampal volume across the 737 participants. However, aerobic exercise had significant positive effects on left hippocampal volume in comparison to control conditions. Post-hoc analyses indicated effects were driven through exercise preventing the volumetric decreases which occur over time.

These results provide meta-analytic evidence for exercise-induced volumetric retention in the left hippocampus. Aerobic exercise interventions may be useful for preventing age-related hippocampal deterioration and maintaining neuronal health.


© 2017 The Authors. Published by Elsevier Inc.


When the Caregiver Needs Care: the Plight of Vulnerable Caregivers

2002 Mar;92(3):409-13.

When the caregiver needs care: the plight of vulnerable caregivers.

Navaie-Waliser M, Feldman PH, Gould DA, Levine C, Kuerbis AN, Donelan K



This study examined the characteristics, activities, and challenges of high-risk informal caregivers.


Telephone interviews were conducted with a nationally representative cross-section of 1002 informal caregivers. Vulnerable caregivers with poor health or a serious health condition were compared with nonvulnerable caregivers.


Thirty-six percent of caregivers were vulnerable. Compared with nonvulnerable caregivers, vulnerable caregivers were more likely to have difficulty providing care, to provide higher-intensity care, to report that their physical health had suffered since becoming a caregiver, to be aged 65 years or older, to be married, and to have less than 12 years of education.


Reliance on informal caregivers without considering the caregiver‘s ability to provide care can create a stressful and potentially unsafe environment for the caregiver and the care recipient.



Does Cognitive Training Prevent Cognitive Decline?

2017 Dec 19. doi: 10.7326/M17-1531. [Epub ahead of print]

Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review.

Butler M, McCreedy E, Nelson VA, Desai P, Ratner E, Fink HA, Hemmy LS, McCarten JR, Barclay TR, Brasure M, Davila H, Kane RL.



Structured activities to stimulate brain function-that is, cognitive training exercises-are promoted to slow or prevent cognitive decline, including dementia, but their effectiveness is highly debated.


To summarize evidence on the effects of cognitive training on cognitive performance and incident dementia outcomes for adults with normal cognition or mild cognitive impairment (MCI).

Data Sources

Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO through July 2017, supplemented by hand-searches.

Study Selection

Trials (published in English) lasting at least 6 months that compared cognitive training with usual care, waitlist, information, or attention controls in adults without dementia.

Data Extraction

Single-reviewer extraction of study characteristics confirmed by a second reviewer; dual-reviewer risk-of-bias assessment; consensus determination of strength of evidence. Only studies with low or medium risk of bias were analyzed.

Data Synthesis

Of 11 trials with low or medium risk of bias, 6 enrolled healthy adults with normal cognition and 5 enrolled adults with MCI. Trainings for healthy older adults were mostly computer based; those for adults with MCI were mostly held in group sessions. The MCI trials used attention controls more often than trials with healthy populations. For healthy older adults, training improved cognitive performance in the domain trained but not in other domains (moderate-strength evidence). Results for populations with MCI suggested no effect of training on performance (low-strength and insufficient evidence). Evidence for prevention of cognitive decline or dementia was insufficient. Adverse events were not reported.


Heterogeneous interventions and outcome measures; outcomes that mostly assessed test performance rather than global function or dementia diagnosis; potential publication bias.


In older adults with normal cognition, training improves cognitive performance in the domain trained. Evidence regarding prevention or delay of cognitive decline or dementia is insufficient.

Primary Funding Source

Agency for Healthcare Research and Quality.


Copyright © 2017 American College of Physicians. All Rights Reserved.


Body Mass Index and Risk of Dementia

2017 Nov 21. pii: S1552-5260(17)33811-6. doi: 10.1016/j.jalz.2017.09.016. [Epub ahead of print]

Body mass index and risk of dementia: Analysis of individual-level data from 1.3 million individuals.

Kivimäki M1, Luukkonen R2, Batty GD3, Ferrie JE4, Pentti J5, Nyberg ST5, Shipley MJ6, Alfredsson L7, Fransson EI8, Goldberg M9, Knutsson A10, Koskenvuo M2, Kuosma E2, Nordin M11, Suominen SB12, Theorell T13, Vuoksimaa E14, Westerholm P15, Westerlund H13, Zins M9, Kivipelto M16, Vahtera J17, Kaprio J14, Singh-Manoux A18, Jokela M19



Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects.


We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis.


Hazard ratios per 5-kg/m2 increase in BMI for dementia were 0.71 (95% confidence interval = 0.66-0.77), 0.94 (0.89-0.99), and 1.16 (1.05-1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis.


The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short.




Caregiving as a Risk Factor for Mortality: the Caregiver Health Effects Study

1999 Dec 15;282(23):2215-9.

Caregiving as a risk factor for mortality: the Caregiver Health Effects Study.

Schulz R1, Beach SR.



There is strong consensus that caring for an elderly individual with disability is burdensome and stressful to many family members and contributes to psychiatric morbidity. Researchers have also suggested that the combination of loss, prolonged distress, the physical demands of caregiving, and biological vulnerabilities of older caregivers may compromise their physiological functioning and increase their risk for physical health problems, leading to increased mortality.


To examine the relationship between caregiving demands among older spousal caregivers and 4-year all-cause mortality, controlling for sociodemographic factors, prevalent clinical disease, and subclinical disease at baseline.


Prospective population-based cohort study, from 1993 through 1998 with an average of 4.5 years of follow-up.


Four US communities.


A total of 392 caregivers and 427 noncaregivers aged 66 to 96 years who were living with their spouses.

Main Outcome Measure

Four-year mortality, based on level of caregiving: (1) spouse not disabled; (2) spouse disabled and not helping; (3) spouse disabled and helping with no strain reported; or(4) spouse disabled and helping with mental or emotional strain reported.


After 4 years of follow-up, 103 participants (12.6%) died. After adjusting for sociodemographic factors, prevalent disease, and subclinical cardiovascular disease, participants who were providing care and experiencing caregiver strain had mortality risks that were 63% higher than noncaregiving controls (relative risk [RR], 1.63; 95% confidence interval [CI], 1.00-2.65). Participants who were providing care but not experiencing strain (RR, 1.08; 95 % CI, 0.61-1.90) and those with a disabled spouse who were not providing care (RR, 1.37; 95% CI, 0.73-2.58) did not have elevated adjusted mortality rates relative to the noncaregiving controls.


Our study suggests that being a caregiver who is experiencing mental or emotional strain is an independent risk factor for mortality among elderly spousal caregivers. Caregivers who report strain associated with caregiving are more likely to die than noncaregiving controls.