Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up

AbstractNoninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer’s disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression. The study sample comprised n = 196 cognitively normal older adults (mean[SD] 72.5 [9.4] years; 114 women [58.2%]) from the Harvard Aging Brain Study. At baseline, all participants underwent structural MRI, DWI, 11C-Pittsburgh compound-B-PET, 18F-flortaucipir-PET imaging, and cognitive assessments. Longitudinal measures of Preclinical Alzheimer Cognitive Composite-5 were available for n = 186 individuals over 3.72 (1.96)-year follow-up. Prospective clinical follow-up was available for n = 163 individuals over 3.2 (1.7) years. Surface-based image analysis assessed vertex-wise relationships between cMD, global amyloid-β, and entorhinal and inferior-temporal tau. Multivariable regression, mixed effects models and Cox proportional hazards regression assessed longitudinal cognition, brain structural changes and clinical progression. Tau, but not amyloid-β, was positively associated with cMD in AD-vulnerable regions. Correcting for baseline demographics and cognition, increased cMD predicted steeper cognitive decline, which remained significant after correcting for amyloid-β, thickness, and entorhinal tau; there was a synergistic interaction between cMD and both amyloid-β and tau on cognitive slope. Regional cMD predicted hippocampal atrophy rate, independently from amyloid-β, tau, and thickness. Elevated cMD predicted progression to mild cognitive impairment. Cortical microstructure is a noninvasive biomarker that independently predicts subsequent cognitive decline, neurodegeneration and clinical progression, suggesting utility in clinical trials.

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Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults

EJNMMI Research ◽

10.1186/s13550-019-0552-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Yoko Shigemoto ◽

Daichi Sone ◽

Miho Ota ◽

Norihide Maikusa ◽

Masayo Ogawa ◽

...

Keyword(s):

Older Adults ◽

Gray Matter ◽

Gray Matter Volume ◽

Cognitively Normal ◽

Matter Volume ◽

The Brain

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P2-324: OPENNESS PERSONALITY TRAIT PREDICTS DELAYED VERBAL RECALL AT >1 YEAR FOLLOW-UP IN COGNITIVELY NORMAL OLDER ADULTS WITHOUT CURRENT OR LIFETIME HISTORY OF PSYCHIATRIC ILLNESS

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.2731 ◽

2019 ◽

Vol 15 ◽

pp. P711-P711

Author(s):

Linda Mah ◽

Frankie Chan ◽

Aliya Ali ◽

Mirjam Mulder-Heijstra ◽

Susan Vandermorris ◽

...

Keyword(s):

Older Adults ◽

Personality Trait ◽

Psychiatric Illness ◽

Cognitively Normal ◽

Verbal Recall ◽

Lifetime History ◽

History Of

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Chronic subsyndromal depression and risk of dementia in older adults

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867420972763 ◽

2020 ◽

pp. 000486742097276

Author(s):

Dae Jong Oh ◽

Ji Won Han ◽

Jong Bin Bae ◽

Tae Hui Kim ◽

Kyung Phil Kwak ◽

...

Keyword(s):

Older Adults ◽

Confidence Interval ◽

Late Onset ◽

Population Based ◽

Hazard Ratio ◽

Cognitively Normal ◽

Subsyndromal Depression ◽

Poor Outcomes ◽

Korean Elderly

Objectives: Subsyndromal depression is prevalent and associated with poor outcomes in late life, but its effect on the risk of dementia has barely been investigated. This study is aimed to investigate the effect of subsyndromal depression on dementia risk in cognitively normal older adults and patients with mild cognitive impairment. Methods: Data were collected from a nationwide, population-based, prospective cohort study on a randomly sampled Korean elderly population aged 60 years or older, which has been followed every 2 years. Using 6-year follow-up data of 4456 non-demented elderly, the authors examined the risk of dementia associated with late-onset subsyndromal depression using multivariate Cox proportional hazard models. After standardized diagnostic interviews, subsyndromal depression and dementia were diagnosed by the operational diagnostic criteria and Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria, respectively. Results: Subsyndromal depression tripled the risk of dementia in non-demented elderly individuals (hazard ratio = 3.02, 95% confidence interval = [1.56, 5.85], p < 0.001). In subgroup analyses, subsyndromal depression was associated with the risk of dementia in cognitively normal participants only (hazard ratio = 4.59, 95% confidence interval = [1.20, 17.54], p = 0.026); chronic/recurrent subsyndromal depression with increasing severity during the follow-up period was associated with the risk of dementia (hazard ratio = 15.34, 95% confidence interval = [4.19, 56.18], p < 0.001). Conclusion: Late-onset subsyndromal depression is a potential predictor of incident dementia when it is chronic or recurrent with increasing severity in cognitively normal older adults.

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Social Participation and the Risk for Developing Mild Cognitive Impairment and Dementia Among Older Adults

Innovation in Aging ◽

10.1093/geroni/igab046.049 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 13-13

Author(s):

Hrafnhildur Eymundsdottir ◽

Sigurveig Sigurdardottir ◽

Alfons Ramel ◽

Palmi Jonsson ◽

Vilmundur Gudnason ◽

...

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Social Participation ◽

Community Dwelling ◽

Cognitively Normal ◽

Frequency Of Contact ◽

Gene Environment ◽

Vitamin D Levels

Abstract Introduction We aim to investigate the longitudinal associations between social participation and the risk of developing mild cognitive impairment (MCI|) and dementia over 5 years of follow-up among cognitively normal older adults. Methods A total of 2802 participants had complete follow-up data from Age-Gene/Environment-Susceptibility-Reykjavik-Study. Social participation was assessed by a questionnaire asking the frequency of contact with children, relatives, friends and neighbors. MCI and dementia were diagnosed according to international guidelines and by a team composed of a geriatrician, neurologist, neuropsychologist, and neuroradiologist. Logistic regression analysis was used to assess the associations. Results At baseline 8% (n=225) reported no social participation. Among cognitively normal participants at baseline, 5.6% (n=243) developed mild cognitive impairment and 2.4% (n= 103) developed dementia during a mean follow-up time of 5.2 years. After full adjustment with covariates including age, gender, education, marital status, vitamin D levels, depression and APOE ε4, those with no social participation at baseline were significantly more likely to develop MCI at follow-up (OR=1.953, P=0.001). However, social participation at baseline was not associated with higher dementia diagnosis at follow-up (OR= 1.490, P=0.194). Conclusions Community-dwelling old adults who are socially inactive are more likely to develop MCI than those who are socially active. Social participation might independently indicate impending changes in cognitive function among older adults.

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Safety and Tolerability of APOE Genotyping and Disclosure in Cognitively Normal Volunteers From the Butler Alzheimer’s Prevention Registry

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988721993575 ◽

2021 ◽

pp. 089198872199357

Author(s):

Jessica Alber ◽

Dominique Popescu ◽

Louisa I. Thompson ◽

Gina-Marie Tonini ◽

Edmund Arthur ◽

...

Keyword(s):

Older Adults ◽

Clinical Trial ◽

Perceived Risk ◽

Functional Independence ◽

Community Dwelling ◽

Self Report ◽

Cognitively Normal ◽

Readiness Screening ◽

Community Dwelling Older Adults

Aims: Alzheimer’s disease (AD) is a gradually progressive neurodegenerative disease that ultimately results in total loss of cognitive and functional independence in older adults. This study aimed to examine the safety and tolerability of APOE disclosure in community-dwelling, cognitively normal (CN) older adults from the Butler Alzheimer’s Prevention Registry (BAPR), and to determine whether APOE disclosure impacted participant’s decisions to participate in AD clinical research. Methods: 186 (N = 106 ∊4 non-carriers, 80 ∊4 carriers) CN older adults aged 58-78 from the BAPR completed 2 visits: one for psychological readiness screening and genotyping and one for APOE disclosure. Online follow-ups were completed 3 days, 6 weeks, and 6 months post-disclosure. Primary outcomes were scores on self-report measures of depression, anxiety, impact of events, and perceived risk of AD, along with enrollment in AD clinical trials. Results: ∊4 carriers and non-carriers did not differ significantly on measures of depression, anxiety, or suicidal ideation over the 6-month follow-up period. ∊4 carriers reported higher impact of disclosure than non-carriers immediately after disclosure, but both groups’ scores on impact of events measures remained sub-clinical. ∊4 carriers and non-carriers were equally likely to participate in AD research after disclosure, with genotype-dependent differences in type of clinical trial enrollment. Conclusions: APOE genotyping and disclosure was safe and well tolerated in a group of CN, community-dwelling older adults, who were pre-screened after volunteering for AD research through BAPR. Implications for the inclusion of APOE genotyping and disclosure at AD clinical trial sites are discussed.

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Age-related Shift in Neural Complexity Related to Task Performance and Physical Activity

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_00725 ◽

2015 ◽

Vol 27 (3) ◽

pp. 605-613 ◽

Cited By ~ 15

Author(s):

Jennifer J. Heisz ◽

Michelle Gould ◽

Anthony R. McIntosh

Keyword(s):

Physical Activity ◽

Older Adults ◽

Information Processing ◽

Cognitive Function ◽

Neural Plasticity ◽

Structural Changes ◽

Local Information ◽

Multiscale Entropy ◽

Age Related ◽

The Brain

The human brain undergoes marked structural changes with age including cortical thinning and reduced connectivity because of the degradation of myelin. Although these changes can compromise cognitive function, the brain is able to functionally reorganize to compensate for some of this structural loss. However, there are interesting individual differences in outcome: When comparing individuals of similar age, those who engage in regular physical activity are less affected by the typical age-related decline in cognitive function. This study used multiscale entropy to reveal a shift in the way the brain processes information in older adults that is related to physical activity. Specifically, older adults who were more physically active engaged in more local neural information processing. Interestingly, this shift toward local information processing was also associated with improved executive function performance in older adults, suggesting that physical activity may help to improve aspects of cognitive function in older adults by biasing the neural system toward local information processing. In the face of age-related structural decline, the neural plasticity that is enhanced through physical activity may help older adults maintain cognitive health longer into their lifespan.

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Neuropsychological Profiles and Trajectories in Preclinical Alzheimer’s Disease

Journal of the International Neuropsychological Society ◽

10.1017/s135561771800022x ◽

2018 ◽

Vol 24 (7) ◽

pp. 693-702 ◽

Cited By ~ 13

Author(s):

Jean K. Ho ◽

Daniel A. Nation ◽

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Executive Function ◽

Processing Speed ◽

Synergistic Effects ◽

Verbal Learning ◽

Semantic Fluency ◽

Cognitively Normal

AbstractObjectives: The present study investigated the independent and synergistic effects of amyloid beta (Aβ1-42) and phosphorylated tau (Ptau) pathologies on neuropsychological profiles and trajectories in cognitively normal older adults. Methods: Alzheimer’s Disease Neuroimaging Initiative participants identified as cognitively normal at baseline underwent longitudinal assessment (N=518; 0, 12, 24, 36 months), baseline lumbar puncture and follow-up cognitive exams. Cerebral spinal fluid (CSF) biomarker profiles (Aβ-Ptau-, Aβ+Ptau-, Aβ-Ptau+, Aβ+Ptau+) were compared on baseline profiles and trajectories for memory (Rey Auditory Verbal Learning Test), attention/executive function (Trail Making Test, A and B), language (Animal Fluency, Vegetable Fluency, Boston Naming Test) and processing speed (Digit Symbol) using multilevel models. Results: The Aβ+Ptau+ group exhibited significantly worse baseline performance on tests of memory and executive function relative to the Aβ-Ptau+ and Aβ-Ptau- groups. The Aβ+Ptau- group fell between the Aβ+Ptau+ participants and the Aβ-Ptau- and Aβ-Ptau+ groups on all three cognitive domains and exhibited worse baseline executive function. The Aβ-Ptau+ group performed worse than Aβ-Ptau- participants on processing speed. Over 36-month follow-up, the Aβ+Ptau+ group exhibited the greatest declines in memory and semantic fluency compared to all other groups. Conclusions: Cognitively normal older adults with both Aβ and Ptau pathology exhibited the weakest profile, marked by the worst memory decline compared to the other groups. Other subtle changes in this group included declines in executive function and semantic fluency. Those with Ptau pathology alone showed slowed processing speed, and those with Aβ pathology alone showed worse attention and executive function compared to biomarker negative participants. (JINS, 2018, 24, 1–10)

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Changes in Regional Brain Grey-Matter Volume Following Successful Completion of a Sensori-Motor Intervention Targeted at Healthy and Fall-Prone Older Adults

Multisensory Research ◽

10.1163/22134808-00002604 ◽

2018 ◽

Vol 31 (3-4) ◽

pp. 317-344 ◽

Cited By ~ 4

Author(s):

Georgia O’Callaghan ◽

Alan O’Dowd ◽

John Stapleton ◽

Niamh A. Merriman ◽

Eugenie Roudaia ◽

...

Keyword(s):

Older Adults ◽

Grey Matter ◽

Structural Changes ◽

Balance Control ◽

Grey Matter Volume ◽

Ageing Population ◽

Precentral Gyrus ◽

Volume Increase ◽

History Of ◽

The Brain

Previous studies have suggested that discrete cross-sensory events could be incorrectly combined in the brain of older adults with a history of falls, possibly undermining motor and balance control. Based on previous findings that multisensory integration is modifiable with practice, even in an ageing population, we designed a serious game, named CityQuest, to train typical, everyday multisensory processes including sensori-motor control, spatial navigation, obstacle avoidance and balance control. Played over several sessions, this game was shown to improve these functions in older adults with and without a history of falls, depending on the specific condition of the game on which they were trained. Here, using voxel-based morphometry analysis of anatomical magnetic resonance imaging (MRI) data, we investigated structural changes in the brain of a smaller group of older adults from those who successfully completed this five-week intervention. A grey-matter (GM) volume increase in the precentral gyrus, and GM volume reduction in the inferior temporal and orbitofrontal gyri, was found for all participants. Changes in GM volume within regions of the cerebellum were differentially associated with fall-prone and healthy older adults. Furthermore, a greater GM volume increase in the precentral gyrus was observed in participants who performed the full CityQuest intervention relative to those required to avoid obstacles only. Our results support previous evidence that multisensory training can affect structural changes in the older brain and have implications for programmes designed for the successful rehabilitation of perceptual and cognitive functions.

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