The hippocampus is one of the most well studied structures in the human brain. While age-related decline in hippocampal volume is well documented, most of our knowledge about hippocampal structure-function relationships was discovered in the context of neurological and neurodegenerative diseases. The relationship between cognitive aging and hippocampal structure in the absence of disease remains relatively understudied. Furthermore, the few studies that have investigated the role of the hippocampus in cognitive aging have produced contradictory results. To address these issues, we assessed 93 older adults from the general community (mean age = 71.9 ± 9.3 years) on the Montreal Cognitive Assessment (MoCA), a brief cognitive screening measure for dementia, and the NIH Toolbox-Cognitive Battery (NIHTB-CB), a computerized neurocognitive battery. High-resolution structural magnetic resonance imaging (MRI) was used to estimate hippocampal volume. Lower MoCA Total (p = 0.01) and NIHTB-CB Fluid Cognition (p < 0.001) scores were associated with decreased hippocampal volume, even while controlling for sex and years of education. Decreased hippocampal volume was significantly associated with decline in multiple NIHTB-CB subdomains, including episodic memory, working memory, processing speed and executive function. This study provides important insight into the multifaceted role of the hippocampus in cognitive aging.

Working memory is an executive memory process that allows transitional information to be held and manipulated temporarily in memory stores before being forgotten or encoded into long-term memory. Working memory is necessary for everyday decision-making and problem solving, making it a fundamental process in the daily lives of older adults. Working memory relies heavily on frontal lobe structures and is known to decline with age. The current study aimed to determine the neural correlates of decreased working memory performance in the frontal lobes by comparing cortical thickness and cortical surface area from two demographically matched groups of healthy older adults, free from cognitive impairment, with high versus low N-Back working memory performance (N=56; average age = 70.29 ± 10.64). High-resolution structural T1-weighted images (1mm isotropic voxels) were obtained on a 3T Philips MRI scanner. When compared to high performers, low performers exhibited significantly decreased cortical surface area in three frontal lobe regions lateralized to the right hemisphere: medial orbital frontal gyrus, inferior frontal gyrus, and superior frontal gyrus (FDR p < 0.05). There were no significant differences in cortical thickness between groups, a proxy for neurodegenerative tissue loss. Our results suggest that decreases in cortical surface area (a proxy for brain structural integrity) in right frontal regions may underlie age-related decline of working memory function.

Transcranial alternating current stimulation (tACS)-a noninvasive brain stimulation technique that modulates cortical oscillations through entrainment-has been demonstrated to alter oscillatory activity and enhance cognition in healthy adults. TACS is being explored as a tool to improve cognition and memory in patient populations with mild cognitive impairment (MCI) and Alzheimer's disease (AD). To review the growing body of literature and current findings obtained from the application of tACS in patients with MCI or AD, highlighting the effects of gamma tACS on brain function, memory, and cognition. Evidence on the use of brain stimulation in animal models of AD is also discussed. Important parameters of stimulation are underscored for consideration in protocols that aim to apply tACS as a therapeutic tool in patients with MCI/AD. The application of gamma tACS has shown promising results in the improvement of cognitive and memory processes that are impacted in patients with MCI/AD. These data demonstrate the potential for tACS as an interventional stand-alone tool or alongside pharmacological and/or other behavioral interventions in MCI/AD. While the use of tACS in MCI/AD has evidenced encouraging results, the effects of this stimulation technique on brain function and pathophysiology in MCI/AD remains to be fully determined. This review explores the literature and highlights the need for continued research on tACS as a tool to alter the course of the disease by reinstating oscillatory activity, improving cognitive and memory processing, delaying disease progression, and remediating cognitive abilities in patients with MCI/AD.

Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), paired with behavioral language therapy, have demonstrated the capacity to enhance language abilities in primary progressive aphasia (PPA), a debilitating degenerative neurological syndrome that leads to declines in communication abilities. The aim of this meta-analysis is to systematically evaluate the efficacy of tDCS and TMS in improving language outcomes in PPA, explore the magnitude of effects between stimulation modalities, and examine potential moderators that may influence treatment effects. Standard mean differences for change in performance from baseline to post-stimulation on language-related tasks were evaluated. Six tDCS studies and two repetitive TMS studies met inclusion criteria and provided 22 effects in the analysis. Random effect models revealed a significant, heterogeneous, and moderate effect size for tDCS and TMS in the enhancement of language outcomes. Findings demonstrate that naming ability significantly improves due to brain stimulation, an effect found to be largely driven by tDCS. Future randomized controlled trials are needed to determine long-term effectiveness of noninvasive brain stimulation techniques on language abilities, further delineate the efficacy of tDCS and TMS, and identify optimal parameters to enable the greatest gains for persons with PPA.

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.