As people age, having both thinking problems and movement problems at the same time—a pattern called a dual cognitive–motor deficit—is known to strongly increase the risk of developing dementia. However, it has not been clear how this combined deficit affects the brain’s structure, especially in vulnerable gray matter regions that are important for memory and movement. This study set out to better understand these brain changes.

The researchers studied 582 adults between the ages of 36 and 90 and grouped them into four categories: those with both cognitive and motor deficits, those with only cognitive deficits, those with only motor deficits, and a control group with neither. They examined brain tissue using advanced MRI techniques, including diffusion tensor imaging and mean apparent propagator imaging, which are well suited for detecting subtle microstructural changes in gray matter and white matter. In total, they analyzed 27 brain regions related to temporal (memory-related) and motor functions, as well as key white matter pathways.

The results showed that people with a dual cognitive–motor deficit had widespread microstructural changes in the brain. These alterations were not seen in individuals who had only cognitive deficits or only motor deficits once rigorous statistical corrections were applied. The observed changes are thought to reflect lower cellular density in temporal gray matter, reduced organization of nerve fibers, and possible loss of myelin in white matter tracts.

Together, these findings suggest that having combined cognitive and motor difficulties is linked to distinct and measurable changes in brain microstructure. Understanding these changes may help explain why this group is at particularly high risk for dementia and could support the development of earlier interventions aimed at slowing brain aging and delaying neurodegeneration.

FIGURE 1

Investigated regions of interest. Three-dimensional rendering of (A) temporal meta-ROIs and motor-related GM regions, and (B) associated WM tracts. A total of 27 ROIs were investigated in the current study. GM, gray matter; ROIs, regions of interest; WM, white matter.

Understanding how the brain changes as we age—especially in conditions like Alzheimer’s disease—is an important area of research. One part of the brain that hasn’t been studied as much is the white matter, which acts like a network of “wires” connecting different brain areas. This large study looked at how the structure of white matter relates to thinking and memory skills in older adults, including those with Alzheimer’s.

Researchers analyzed data from 9 separate studies, including nearly 4,500 adults aged 50 and older. Participants had brain scans using a technique called diffusion MRI (dMRI), along with memory and thinking tests over time. Most participants were cognitively healthy, while some had mild memory problems or Alzheimer’s dementia. The study focused on a specific feature of white matter called “free water” (FW), which can indicate damage or degeneration.

They found that higher levels of FW in white matter—especially in regions connected to memory like the cingulum and fornix—were strongly linked to worse memory and faster cognitive decline. These changes were even more noticeable in people who had other signs of Alzheimer’s, such as brain shrinkage, a genetic risk factor called APOE ε4, or positive tests for amyloid buildup (a hallmark of Alzheimer’s).

Overall, the study shows that changes in white matter—particularly FW—are an important piece of the puzzle in understanding memory loss and aging. These findings suggest that future brain studies should pay close attention to FW and highlight the importance of brain regions like the cingulum and fornix in Alzheimer’s-related decline.

Figure 1. ��Cohort Characteristics and Data Harmonization

A, Participants were drawn from 9 well-established cohorts, including 3213 cognitively unimpaired (CU) individuals, 972 with mild cognitive impairment (MCI), and 282 with Alzheimer disease (AD) at baseline. B, The study also incorporated longitudinal data across 9208 cognitive sessions, spanning up to 13 years of follow-up. Longitudinal ComBat harmonization was applied to all imaging features to account for variability across imaging batches. C and D, Associations are shown between cingulum free-water (FW) and memory performance, using both raw (C) and harmonized (D) FW data, with points and lines color coded by imaging batch. Harmonized data were used across all analyses. ADNI indicates Alzheimer’s Disease Neuroimaging Initiative; BIOCARD, Biomarkers of Cognitive Decline Among Normal Adults; BLSA, Baltimore Longitudinal Study of Aging; MAP, Rush Memory and Aging Project; MARS, Minority Aging Research Study; NACC, National Alzheimer’s Coordinating Center; ROS, Religious Orders Study; VMAP, Vanderbilt Memory and Aging Project; WRAP, Wisconsin Registry for Alzheimer’s Prevention.

As more older adults become candidates for liver transplants, it’s increasingly important to distinguish between dementia caused by aging and��hepatic encephalopathy (HE)—a condition related to liver dysfunction. These two conditions can appear very similar in how they affect thinking and memory. While��neuropsychological testing (NPT)��is commonly used to evaluate dementia, imaging techniques like��FDG PET/CT scans, which measure brain activity, are being explored as faster alternatives. This preliminary study looks at how useful FDG PET/CT is for detecting irreversible dementia in older people being considered for a liver transplant.��

Eighteen patients showing signs of possible dementia during their transplant evaluations received an FDG PET/CT brain scan. The study compared the PET/CT scan results to NPT results and also looked at how long each test took to produce a diagnosis. Brain scan results were also compared to healthy individuals of the same age to see if there were noticeable differences in brain activity.��

In 40% of the patients, the PET/CT scan identified signs of irreversible dementia. The scan results moderately agreed with the NPT results, and while the scan was highly sensitive (able to catch all cases of dementia), it wasn’t as specific (sometimes showing false positives). Importantly, the PET/CT scan delivered results much faster—on average in about 12 days, compared to over 70 days for NPT. The scans also revealed significant reductions in brain activity in areas linked to thinking and movement, compared to healthy individuals.��

These findings suggest that��FDG PET/CT scans could be a useful early tool��in identifying irreversible causes of dementia in older liver transplant patients. However, a positive scan should not be the sole reason to rule someone out of receiving a transplant; it should lead to further testing. Using PET/CT scans as an initial screening step could speed up the evaluation process and help ensure that patients who need further care get it in time.��

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Fig. 1��

Results from matched case-control comparison of FDG PET scans of the brain. Cases (patients referred for FDG PET for cognitive symptoms during transplant evaluation) had significantly decreased fluorodeoxyglucose (FDG) uptake in multiple large clusters (outlined in white) primarily in the frontal, temporal, and parietal lobes compared to healthy age- and sex-matched controls from the Alzheimer’s Disease Neuroimaging Initiative database (ADNI). These T-statistic maps show the regional statistical differences in glucose metabolism in the brain between 16 case-control pairs. Blue reflects voxels where cases had decreased FDG uptake vs. controls, while red reflects the opposite. Clusters that reach significance (FDR < 0.05 and voxel-extent of 10) are outlined in white. No significant clusters of increased SUVR were observed.

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Cognitive and mobility decline together (dual decline) is more strongly linked to the risk of developing dementia than cognitive decline alone. However, it’s still unclear whether this condition is related to certain patterns of brain shrinkage, damage to white matter (the tissue that connects brain regions), or other brain changes. ��

In the Baltimore Longitudinal Study of Aging, we studied participants with and without dual decline to compare changes in brain images, white matter damage, and specific biomarkers over up to 13 years. We looked at brain atrophy, white matter issues, and proteins in the blood that are linked to brain health, including markers for neurodegeneration like GFAP, NfL, amyloid beta, and tau. ��

Our results showed that people with dual decline experienced faster shrinkage in brain regions related to memory, movement, and language. Those with only mobility problems had brain shrinkage in one specific area, while those with memory decline had a different pattern. Dual decline also showed damage to white matter in several brain areas and a greater decline in the amyloid beta ratio, which is a sign of Alzheimer’s disease. Additionally, there were higher levels of proteins linked to brain damage in the blood. ��

In conclusion, individuals with dual decline may be at greater risk for brain shrinkage, white matter damage, and specific changes in biomarkers that could lead to dementia. This highlights the importance of dual decline as a potential signal of underlying brain and blood changes associated with dementia.��

FIGURE 1��

Flow chart of sample selection criteria. AD, Alzheimer’s disease; Aβ42/40, amyloid beta 42/40 ratio; DTI, diffusion tensor imaging; GFAP, glial fibrillary acidic protein; MRI, magnetic resonance imaging; NfL, neurofilament light chain; pTau181, phosphorylated tau.��

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Researchers are investigating how heart failure with preserved ejection fraction (HFpEF) may affect brain structure in dementia patients. A study at ������ý���� Medical Center analyzed brain images from dementia patients with and without HFpEF, revealing that those with HFpEF showed significant atrophy in specific brain regions linked to emotion, sensory processing, and decision-making. This suggests that HFpEF could contribute to distinctive patterns of brain damage in dementia, highlighting the need for further research into targeted treatments for these patients.