Early cortical microstructural changes in aging are linked to vulnerability to Alzheimer's disease pathology.

BACKGROUND: Early identification of Alzheimer's disease (AD) risk is critical for improving treatment success. Cortical thickness is a macrostructural measure used to assess AD neurodegeneration. However, cortical microstructural changes appear to precede macrostructural atrophy and may improve early risk identification. Currently, whether cortical microstructural changes in aging are linked to vulnerability to AD pathophysiology remains unclear in non-clinical populations, who are precisely the target for early risk identification. METHODS: In 194 adults, we calculated MRI-derived maps of changes in cortical mean diffusivity (microstructure) and cortical thickness (macrostructure) over 5-6 years (meanage: Time1=61.82; Time2=67.48). Episodic memory was assessed using three well-established tests. We obtained PET-derived maps of AD pathology deposition (beta-amyloid, tau) and neurotransmitter receptors (cholinergic, glutamatergic) implicated in AD pathophysiology. Spatial correlational analyses were used to compare pattern similarity among maps. RESULTS: Spatial patterns of cortical macrostructural changes resembled patterns of cortical organization sensitive to age-related processes (r=-0.31, p<0.05), whereas microstructural changes resembled the patterns of tau (r=0.39, p=0.015) deposition in AD. Individuals with patterns of microstructural changes that more closely resembled stereotypical tau deposition exhibited greater memory decline (ß=0.21, p=0.036). Microstructural changes and AD pathology deposition were enriched in areas with greater densities of cholinergic and glutamatergic receptors (ps<0.05). CONCLUSIONS: Patterns of cortical microstructural changes were more AD-like than patterns of macrostructural changes, which appeared to reflect more general aging processes. Microstructural changes may better inform early risk prediction efforts as a sensitive measure of vulnerability to pathological processes prior to overt atrophy and cognitive decline.

Probable chronic pain, brain structure, and Alzheimer's plasma biomarkers in older men.

Chronic pain leads to tau accumulation and hippocampal atrophy in mice. In this study, we provide one of the first assessments in humans, examining the associations of probable chronic pain with hippocampal volume, integrity of the locus coeruleus (LC)-an upstream site of tau deposition-and Alzheimer's Disease-related plasma biomarkers. Participants were mostly cognitively unimpaired men. Probable chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, 424 participants underwent structural magnestic resonance imaging (MRI) of hippocampal volume and LC-sensitive MRI providing an index of LC integrity (LC contrast-to-noise ratio). Analyses adjusted for confounders including major health conditions, depressive symptoms, and opioid use. Models showed that men with probable chronic pain had smaller hippocampal volume and lower rostral-middle-but not caudal-LC contrast-to-noise ratio compared to men without probable chronic pain. Men with probable chronic pain also had higher levels of plasma total tau, beta-amyloid-42, and beta-amyloid-40 compared to men without probable chronic pain. These findings suggest that probable chronic pain is associated with tau accumulation and reduced structural brain integrity in regions affected early in the development of Alzheimer's Disease. PERSPECTIVE: Probable chronic pain was associated with plasma biomarkers and brain regions that are affected early in Alzheimer's disease (AD). Reducing pain in midlife and elucidating biological mechanisms may help to reduce the risk of AD in older adults.

Childhood Disadvantage Moderates Late Midlife Default Mode Network Cortical Microstructure and Visual Memory Association.

BACKGROUND: Childhood disadvantage is a prominent risk factor for cognitive and brain aging. Childhood disadvantage is associated with poorer episodic memory in late midlife and functional and structural brain abnormalities in the default mode network (DMN). Although age-related changes in DMN are associated with episodic memory declines in older adults, it remains unclear if childhood disadvantage has an enduring impact on this later-life brain-cognition relationship earlier in the aging process. Here, within the DMN, we examined whether its cortical microstructural integrity-an early marker of structural vulnerability that increases the risk for future cognitive decline and neurodegeneration-is associated with episodic memory in adults at ages 56-66, and whether childhood disadvantage moderates this association. METHODS: Cortical mean diffusivity (MD) obtained from diffusion magnetic resonance imaging was used to measure microstructural integrity in 350 community-dwelling men. We examined both visual and verbal episodic memory in relation to DMN MD and divided participants into disadvantaged and nondisadvantaged groups based on parental education and occupation. RESULTS: Higher DMN MD was associated with poorer visual memory but not verbal memory (ß = -0.11, p = .040 vs ß = -0.04, p = .535). This association was moderated by childhood disadvantage and was significant only in the disadvantaged group (ß = -0.26, p = .002 vs ß = -0.00, p = .957). CONCLUSIONS: Lower DMN cortical microstructural integrity may reflect visual memory vulnerability in cognitively normal adults earlier in the aging process. Individuals who experienced childhood disadvantage manifested greater vulnerability to cortical microstructure-related visual memory dysfunction than their nondisadvantaged counterparts who exhibited resilience in the face of low cortical microstructural integrity.

Lumbar Stenosis Spinal Surgery-Associated Cerebrospinal Fluid Leak Without Headache: An Autobiographical Case Report.

Lumbar spinal stenosis, a narrowing of the spinal canal around the spinal neurovascular structures, is a common etiology for lower back and leg pain in older people. Sciatica, a frequent symptom of lumbar spinal stenosis, typically presents with sharp and/or aching pain that originates in the buttock, extends to the thigh, and radiates into the foot and toes; in addition, it can be accompanied by weakness of the associated lower extremity. In individuals with sciatica-related persistent symptoms or functional limitations or both, spinal decompression surgery may be necessary. A cerebrospinal fluid leak is a potential complication of lumbar spinal stenosis surgery; it is frequently--yet not always--accompanied by a postural headache. The cerebrospinal fluid leak can result from an intraoperative tear or postoperatively. Albeit a more common adverse event after body contouring surgery, seroma--a postoperative serous fluid collection that is usually detectable as a palpable or visible fluid wave on clinical examination--has also been observed as a complication following lumbar spinal stenosis surgery. A man who experienced an intra-operative accidental dural tear during lumbar spinal stenosis surgery is described. A large cerebrospinal fluid leak that involved both the laminectomy bed and the subcutaneous tissue of his back subsequently developed; the leak eventually presented as duro-cutaneous fistulas without headache. His doctors misinterpreted the cerebrospinal fluid leak as a seroma; this may have occurred since not only did the color of the persistent and continuously dripping fluid varied from being clear to slightly tinged pink, but also the patient never had a headache or any other symptoms associated with a cerebrospinal fluid leak. When his lower back was appropriately evaluated with magnetic resonance imaging, the diagnosis of a large cerebrospinal fluid leak was established. In conclusion, lumbar spinal stenosis back surgery can be associated with postoperative complications, including cerebrospinal fluid leak and--less frequently--seroma. However, following lumbar spinal stenosis surgery, the absence of a headache does not exclude the possibility of a cerebrospinal fluid leak. Also, the presence of fluid leaking from the surgical site after lumbar spinal stenosis back surgery should not only prompt the clinician to entertain the possibility of a surgery-associated cerebrospinal fluid leak but also to obtain additional diagnostic studies--such as magnetic resonance imaging--to establish the diagnosis.