Development of dementia in older adults : the body-mind connection

Over the past years, two major lines have emerged in the field of dementia research that are focused on: (1) The accurate and early prediction of dementia, and (2) The identification of modifiable factors for dementia prevention. This thesis has contributed to both. We explored the role played by the body-mind connection in cognitive aging by investigating whether motor functioning is a predictor of dementia and if different co-occurring diseases (i.e., multimorbidity [MM] patterns) are risk factors for dementia. We carried out four longitudinal studies, two for each research line, using 12 years of data from SNAC-K, a population-based study involving 3363 older adults, clinically assessed at regular intervals.

Study I. Participants with both cognitive and motor dysfunctions demonstrated the highest hazard of developing dementia. After gait speed was added to cognitive assessment, the area under the curve (AUC) increased from 0.69 to 0.83 among the oldest participants. This increase was driven by a reduction in the proportion of false negatives, while the number of false positives (high specificity) remained low. Adding gait speed did not improve the predictive power of the cognitive battery in identifying dementia among younger-old adults. Study II. Individuals with concurrent cognitive and motor decline presented with a mixed and more rapidly evolving brain pathology on magnetic resonance imaging, affecting both gray and white matter. Adults experiencing only cognitive decline had a steeper hippocampal volume loss, whereas those exhibiting only motor decline displayed greater white matter hyperintensity burden. Study III. Individuals belonging to the neuropsychiatric, cardiovascular, and sensory impairment/cancer MM-patterns had the highest hazards of dementia, among those with MM. Inflammation (high C-reactive protein levels) increased dementia hazard within these three patterns, whereas being an APOE ε4-carrier heightened dementia hazard for neuropsychiatric and cardiovascular MM-patterns. Study IV. Exposure to air particulate matter ≤ 2.5μm [PM2.5] was found to increase dementia hazard by up to 50%. The presence of heart diseases (heart failure and ischemic heart disease) further amplified the risk, whereas stroke mediated up to 50% of the PM2.5-dementia association.

Conclusions. The findings from these four studies underline the relevance of the body-mind connection in dementia development. An easy-to-obtain motor marker (gait speed) improved the ability of the cognitive test to detect future dementia. This could be explained by the mixed brain pathology, which we found to develop in individuals with fast and concomitant cognitive and motor decline. Specific MM-patterns seemed to increase dementia risk, an effect that was further accentuated by the presence of inflammation and genetic predisposition. Finally, cardiovascular diseases could be important in explaining the relation between PM2.5 and dementia risk. Further exploring the relation between body- and mind-related conditions could be essential in identifying at-risk populations and biomarkers for incipient dementia, and thus, in advancing our understanding of dementia in older adults.

List of scientific papers

I. Grande G, Rizzuto D, Vetrano DL, Marseglia A, Vanacore N, Laukka JE, Welmer AK, Fratiglioni L. Cognitive and physical markers of prodromal dementia: A 12-year-long population study. Alzheimers Dement. 2020;16(1):153-161.
https://doi.org/10.1002/alz.12002

II. Grande G, Vetrano DL, Kalpouzos G, Welmer AK, Marseglia A, Fratiglioni L, Rizzuto D. Brain changes as the biological substrate of fast cognitive and motor decline: results from the SNACK-MRI study. [Submitted]

III. Grande G, Marengoni A (co-first author), Vetrano DL, Roso-Llorach A, Rizzuto D, Zucchelli A, Qiu C, Fratiglioni L, Calderón-Larrañaga A. Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics. Alzheimers Dement. [Accepted]
https://doi.org/10.1002/alz.1223.

IV. Grande G, Ljungman PLS, Eneroth K, Bellander T, Rizzuto D. Association Between Cardiovascular Disease and Long-term Exposure to Air Pollution With the Risk of Dementia. JAMA Neurol. 2020;77(7):801-809.
https://doi.org/10.1001/jamaneurol.2019.4914