Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

Background and objectives: There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. Methods: We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Results: Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Conclusion: Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Quinolone-Induced Painful Peripheral Neuropathy: A Case Report and Literature Review.

We present a case report of a 20-year-old male with diabetes mellitus type 1, who developed severe painful peripheral neuropathy while on the second of a 10-day course with levofloxacin for the treatment of epididymitis. The intensity of the pain rapidly reached scores of 10/10 in a numeric scale 0/10, and the patient was transferred to an inpatient pain unit where he was treated aggressively with minimal improvement. A skin biopsy revealed small fiber neuropathy. Then the patient was treated with intravenous immunoglobulin, which improved the pain. Now the patient is on outpatient intravenous immunoglobulin infusions bimonthly and making a slow recovery.

Stress induced neural reorganization: A conceptual framework linking depression and Alzheimer's disease.

Chronic stress is a risk factor for a number of physiological disorders including cardiovascular disease, obesity and gastrointestinal disorders, as well as psychiatric and neurodegenerative disorders. There are a number of underlying molecular and cellular mechanisms altered in the course of chronic stress, which may increase the vulnerability of individuals to develop psychiatric disorders such as depression, and neurodegenerative disorders such as Alzheimer's Disease (AD). This is evident in the influence of stress on large-scale brain networks, including the resting state Default Mode Network (DMN), the effects of stress on neuronal circuitry and architecture, and the cellular and molecular adaptations to stress, which may render individuals with stress related psychiatric disorders more vulnerable to neurodegenerative disease later in life. These alterations include decreased negative feedback inhibition of the hypothalamic pituitary axis (HPA) axis, decreased dendritic arborization and spine density in the prefrontal cortex (PFC) and hippocampus, and the release of proinflammatory cytokines, which may suppress neurogenesis and promote neuronal cell death. Each of these factors are thought to play a role in stress-related psychiatric disease as well as AD, and have been observed in clinical and post-mortem studies of individuals with depression and AD. The goal of the current review is to summarize clinical and preclinical evidence supporting a role for chronic stress as a putative link between neuropsychiatric and neurodegenerative disease. Moreover, we provide a rationale for the importance of taking a medical history of stress-related psychiatric diseases into consideration during clinical trial design, as they may play an important role in the etiology of AD in stratified patient populations.

The influence of beta-blockers on delayed memory function in people with cognitive impairment.

Adrenergic signaling is important for the retrieval of intermediate-term contextual and spatial memories. The role of norepinephrine in retrieval requires signaling through beta1-adrenergic receptors in the hippocampus. Environmental cues activate the locus ceruleus, the main adrenergic nucleus of the brain, when an environmental stimulus is memorable. This leads to norepinephrine activation in the hippocampus, which is important for retrieving memories. Although beta-blockers do not impair cognition in normal subjects, this article explores the possibility that central nervous system (CNS)-active beta-blockers could affect delayed memory in patients with cognitive impairment. The authors investigated the influence of beta-blockers on delayed memory function in cognitively impaired patients. There was a trend for worse delayed memory retrieval in patients who were on CNS-active beta-blockers. These data support the notion that common medications used in cognitively impaired elderly patients can worsen cognition and that careful selection of medications may help to maximize retrieval of newly formed memories.

Applicability of long-term electroencephalography in pre-mortem diagnosis of Creutzfeldt-Jakob disease: A case report.

Creutzfeldt-Jakob disease accounts for more than 90% of all sporadic prion disease cases. The molecular MM2 genotype has been divided into cortical and thalamic subtypes based on structures involved and is characterized clinically by progressive dementia without ataxia or typical electroencephalography changes. Proposed diagnostic criteria for MM2 cortical type sporadic Creutzfeldt-Jakob disease include progressive dementia, cortical hyper-intensity on diffusion-weighted magnetic resonance imaging, increased cerebrospinal fluid 14-3-3 protein level, and the exclusion of other types of dementia. The presence of periodic discharges on electroencephalography in MM2 cortical type were reported in 42% of the cases. We are reporting a case of sporadic Creutzfeldt-Jakob disease cortical MM2-type presenting with rapid cognitive decline, who survived 8 months since symptom onset. Brain imaging, cerebrospinal fluid analysis, and long-term electroencephalography monitoring were obtained and diagnosis was confirmed by autopsy. Short-term electroencephalography recording, performed 5 months after symptom onset, demonstrated diffuse background slowing without epileptiform activity. Long-term video electroencephalography monitoring demonstrated generalized slowing, maximum in bilateral frontal areas, which intermittently would become rhythmic (1-2 Hz) without hemispheric predominance. If the findings do not clearly meet the proposed clinical criteria for sporadic Creutzfeldt-Jakob disease, the use of long-term electroencephalography could increase the sensitivity. We question whether the lack of the characteristic findings on electroencephalography in some cases could be due to insufficient time of recording. Application of long-term electroencephalography monitoring increases the sensitivity of electroencephalography and the certainty of pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease.

A case report of anxiety disorder preceding frontotemporal dementia with asymmetric right temporal lobe atrophy.

Behavioral variant frontotemporal dementia presents with progressive loss of social skills and cognition and is usually associated with asymmetric frontal or temporal lobe involvement. This article reports about a patient with a long history of anxiety disorder who later proceeded to develop behavioral variant frontotemporal dementia. Further discussion about selective specific network vulnerability and a possible link between these two conditions is provided.

Ataxia, ophthalmoplegia, and impairment of consciousness in a 19-month-old American boy.

A 19-month-old, white, Pennsylvanian boy, with an unremarkable medical history, presented to our hospital with a 3-week history of nonbloody, nonbilious emesis up to 5 times a day and nonbloody diarrhea. Ten days before admission, his gait became progressively unsteady, until he finally refused to walk. A day before admission, he found it difficult to move his eyes. The patient was hypoactive. History, physical and neurologic examination, blood and cerebrospinal (CSF) fluid studies, and neuroimaging studies ruled out the most frequent causes of acute ataxia. The etiology of bilateral, complete ophthalmoplegia was also taken into consideration. Magnetic resonance imaging (MRI) findings of bilateral thalami and mammillary bodies provided diagnostic clues. Additional history and specific tests established the final diagnosis and treatment plan. The patient improved to a normal neurologic state. This case provides important practical information about an unusual malnutrition cause of acute ataxia, particularly in young children of developing countries.

Primary progressive aphasia: clinical, imaging, and neuropathological findings.

Primary Progressive Aphasia (PPA) is a neurodegenerative disorder initially presenting with progressive language imapirment. This article provides a clinically oriented review of PPA. Different clinical presentations and imaging findings of 3 subtypes, agrammatic, semantic and logopenic, are presented. Underlying neuropathology, medical and social management aspects of these patients are reviewed.

Cerebrospinal immunoglobulin level changes and clinical response to treatment of Hashimoto's encephalopathy.

We describe a 64-year-old male who presented with a 2-year history of behavioral and cognitive decline. Brain imaging showed nonenhancing hemispheric white matter lesions. Blood work revealed elevated thyroglobulin and thyroperoxidase antibody levels. Cerebrospinal fluid (CSF) analysis was largely negative, except for an elevated protein and immunoglobulin G (IgG) level. Because of the absence of stroke, central nervous system (CNS) tumor, or infection, this patient fits into criteria of Hashimoto's encephalopathy. His Mini-Mental State Examination score improved from 10 to 29 after initial immunotherapy. The patient remained stable over 6 months with monthly outpatient total plasma exchange, but symptoms recurred within 3 months when the outpatient therapy was discontinued. A follow-up CSF IgG level was found to be increased and the treatment was repeated with partial clinical improvement and decline in CSF IgG level. He then underwent high dose steroid treatment after which patients' clinical condition stabilized and CSF analysis showed even further IgG decline.

Progranulin and beta-amyloid distribution: a case report of the brain from preclinical PS-1 mutation carrier.

BACKGROUND: Progranulin (PGRN) is a multifunctional growth factor that is found in many tissues. Mutations in the PGRN gene cause familial frontotemporal dementia with ubiquitin-positive inclusions. PGRN plaque-like structures have been described in Alzheimer's disease (AD), in association with beta-amyloid (Abeta) plaques. OBJECTIVE: To investigate PGRN and aggregated Abeta immunolabeling distribution in autopsied brain tissue from the participant with confirmed PS-1 (A246E) mutation, who died prior to clinical symptom onset. RESULTS: Immunolabeling for PGRN was positive and accumulated/formed plaque-like structures in all studied regions. These structures most frequently colocalized with Abeta though there were some that did not. PGRN plaques were most dense in medial temporal and frontal regions and predominated over aggregated Abeta. CONCLUSIONS: This case report illustrates PGRN accumulation and Abeta aggregation in preclinical PS-1 AD case and raises the question whether this phenomenon coincides with or precedes Abeta aggregation.