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Objective To investigate the association of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD) and MRI measures of brain atrophy and white matter hyperintensities (WMH). Methods Thirty-seven patients with probable AD received the Neuropsychiatric Inventory (NPI), the Mini Mental Status Exam (MMSE), and an MRI scan as part of their initial evaluation at the Outpatient Memory Diagnostic Clinic at McLean Hospital. MRI-based volumetric measurements of whole brain atrophy, hippocampal volumes and WMH were obtained. Analysis of covariance models, using age as a covariate and the presence of specific BPSD as independent variables, were used to test for differences in whole brain volumes, hippocampal volumes and WMH volumes. Results Increased WMH were associated with symptoms of anxiety, aberrant motor behavior, and nighttime disturbance, while symptoms of disinhibition were linked to lower WMH volume. No associations were found for of whole brain or hippocampal volumes and BPSD. Conclusions These findings suggest that white matter changes are associated with the presence of BPSD in AD.

Age-related memory impairments have been linked to differences in structural brain parameters, including the integrity of the hippocampus (HC) and its distinct hippocampal subfields (HCsf). Imaging methods sensitive to the underlying tissue microstructure are valuable in characterizing age-related HCsf structural changes that may relate to cognitive function. Magnetic resonance elastography (MRE) is a noninvasive MRI technique that can quantify tissue viscoelasticity and may provide additional information about aging effects on HCsf health. Here, we report a high-resolution MRE protocol to quantify HCsf viscoelasticity through shear stiffness, μ, and damping ratio, ξ, which reflect the integrity of tissue composition and organization. HCsf exhibit distinct mechanical properties—the subiculum had the lowest μ and both subiculum and entorhinal cortex had the lowest ξ. Both measures correlated with age: HCsf μ was lower with age (P < 0.001) whereas ξ was higher (P = 0.002). The magnitude of age-related differences in ξ varied across HCsf (P = 0.011), suggesting differential patterns of brain aging. This study demonstrates the feasibility of using MRE to assess HCsf microstructural integrity and suggests incorporation of these metrics to evaluate HC health in neurocognitive disorders.

Introduction:How frequent and how clinically important are mood and behavioral symptoms among older adults with mild cognitive impairment (MCI)? Although these noncognitive behavioral symptoms (NCBS) are not represented in the diagnostic criteria for MCI, their clinical significance is increasingly recognized.Methods:To address this question, the authors identified a cohort of consecutively evaluated patients from a psychiatric hospital's outpatient memory clinic. These patients' records contained both a clinical assessment and a standardized set of evaluations including the Mini-Mental State Exam, the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale. Using a standardized chart-review approach, the presence of any NPI-screened symptom was identified and the frequencies of specific NPI-screened symptoms were calculated for the Memory Clinic MCI cohort and for amnestic and non-amnestic MCI subgroups.Results:A total of 116 patient records were reviewed. Thirty-eight patients with MCI were identified. Twenty-two of these met criteria for amnestic MCI by Mayo Clinic criteria while 16 met criteria for non-amnestic MCI. At least one NPI-screened mood or behavioral symptom was present in 86.8% of these MCI patients. Depression/dysphoria (63.3%), apathy (60.5%), anxiety (47.4%), irritability (44.7%), and nighttime behaviors (42.1%) were the most frequent. While depression/dysphoria was distributed similarly between amnestic and non-amnestic subgroups, apathy was significantly more frequently associated with the amnestic subtype of MCI, and nighttime behaviors were more frequently associated with the non-amnestic subtype.Conclusion:Although the presence of NCBS is not required for a diagnosis of MCI, these symptoms are frequently present and constitute an important source of morbidity. Apathy and depression may be difficult to differentiate, but targeted treatment of depression may fail to address apathy. Recognizing the limitations of this preliminary study, the authors suggest that apathy may be more characteristic of amnestic MCI while nighttime behaviors may be more characteristic of non-amnestic MCI.

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Dementia (major neurocognitive disorder) is an increasingly common syndrome with a significant burden on patients, caregivers, the health-care system, and the society. The prevalence of dementia will certainly continue to grow as the US population ages. Current treatments for dementia, though, are limited. One proposed nonpharmacologic approach for the delay or prevention of dementia is the use of a ketogenic diet. The ketogenic diet was originally employed to treat refractory epilepsy and has shown promise in many neurologic diseases. It has also gained recent popularity for its weight loss effects. Several preclinical studies have confirmed a benefit of ketosis on cognition and systemic inflammation. Given the renewed emphasis on neuroinflammation as a pathogenic contributor to cognitive decline, and the decreased systemic inflammation observed with the ketogenic diet, it is plausible that this diet may delay, ameliorate, or prevent progression of cognitive decline. Several small human studies have shown benefit on cognition in dementia with a ketogenic diet intervention. Future, large controlled studies are needed to confirm this benefit; however, the ketogenic diet has shown promise in regard to delay or mitigation of symptoms of cognitive decline.

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