Purpose of review

People over 90 are the fastest growing segment of the population with the highest rates of dementia. This review highlights recent findings that provide insight to our understanding of dementia and cognition at all ages.

Recent findings

Risk factors for Alzheimer's disease (AD) and dementia differ by age, with some factors, like the development of hypertension, actually becoming protective in the oldest-old. At least half of all dementia in this age group is due to non AD pathologies, including microinfarcts, hippocampal sclerosis and TDP-43. The number of pathologic changes found in the brain is related to both risk and severity of dementia, but many people in this age group appear to be 'resilient' to these pathologies. Resilience to Alzheimer pathology, in part, may be related to absence of other pathologies, and imaging and spinal fluid biomarkers for AD have limited utility in this age group.

Summary

Studies of dementia in the oldest-old are important for our understanding and eventual treatment or prevention of dementia at all ages.

Abstract Objective: To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest-old. Background: Cognitive functioning in individuals aged 90 years and older (the oldest-old) is determined by multiple factors. The association between cognitive impairment and individual pathologies seems to become weaker at older ages. It remains however unknown how these different pathologies interact in the oldest-old. Design/Methods: Participants were 141 individuals (94 cognitively normal and 47 cognitively impaired). Each participant completed a brain MRI scan. Cognitive testing was performed every six months with a mean follow-up of 2.0 years and included the following tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, Trail Making Test (TMT) A, B and C. One linear mixed model was used for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume with cognition. Models were adjusted for age, gender and education. Results: Mean age of the study sample was 94.3 (SD=3.2) years. At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall and TMT B. Lower hippocampal volumes were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower hippocampal volumes were associated with faster decline in the 3MS and MMSE and lower hippocampal volume was also associated with faster decline in the CVLT immediate recall. There was no association between WMH and hippocampal volume and no interaction between WMH and hippocampal volume in their association with baseline cognition or cognitive decline. Conclusions: The research shows that WMH and hippocampal atrophy have an independent, and not synergistic, negative effect on cognition in the oldest-old.

Objectives

To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.

Design

Ongoing longitudinal study.

Setting

In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.

Participants

Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment).

Measurements

Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education.

Results

Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline.

Conclusion

We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019.

Objectives

To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.

Design

Ongoing longitudinal study.

Setting

In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.

Participants

Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment).

Measurements

Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education.

Results

Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline.

Conclusion

We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019.