CNS Ageing in Health and Neurodegenerative Disorders

Kesidou, Evangelia; Theotokis, Paschalis; Damianidou, Olympia; Boziki, Marina; Konstantinidou, Natalia; Taloumtzis, Charilaos; Sintila, Styliani-Aggeliki; Grigoriadis, Panagiotis; Evangelopoulos, Maria Eleptheria; Bakirtzis, Christos; Simeonidou, Constantina

doi:10.3390/jcm12062255

Cited by 15 publications

(8 citation statements)

References 139 publications

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“…It has been suggested, however, that the pathophysiology of MS changes with disease progression; from primarily inflammatory to less inflammatory and predominantly neurodegenerative in the late stages of the disease [77]. In progressive MS, additional mechanisms of axonal loss coexist, such as ionic overload, mitochondrial dysfunction, iron dysregulation, and glutamate excitotoxicity, which are at least partly independent of the mild apparent inflammation within the CNS [78,79]. In addition to that, and due to the multifunctional role of CP in brain homeostasis, it is difficult to distinguish the dominant purpose of volume enlargement, even in normal aging [73].…”

Section: Discussionmentioning

confidence: 99%

The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis

Andravizou,

Stavropoulou De Lorenzo,

Kesidou

et al. 2024

Healthcare

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Choroid plexus (CP) can be seen as a watchtower of the central nervous system (CNS) that actively regulates CNS homeostasis. A growing body of literature suggests that CP alterations are involved in the pathogenesis of multiple sclerosis (MS) but the underlying mechanisms remain elusive. CPs are enlarged and inflamed in relapsing-remitting (RRMS) but also in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) stages, far beyond MS diagnosis. Increases in the choroid plexus/total intracranial volume (CP/TIV) ratio have been robustly associated with increased lesion load, higher translocator protein (TSPO) uptake in normal-appearing white matter (NAWM) and thalami, as well as with higher annual relapse rate and disability progression in highly active RRMS individuals, but not in progressive MS. The CP/TIV ratio has only slightly been correlated with magnetic resonance imaging (MRI) findings (cortical or whole brain atrophy) and clinical outcomes (EDSS score) in progressive MS. Therefore, we suggest that plexus volumetric assessments should be mainly applied to the early disease stages of MS, whereas it should be taken into consideration with caution in progressive MS. In this review, we attempt to clarify the pathological significance of the temporal CP volume (CPV) changes in MS and highlight the pitfalls and limitations of CP volumetric analysis.

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Section: Discussionmentioning

confidence: 99%

The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis

Andravizou,

Stavropoulou De Lorenzo,

Kesidou

et al. 2024

Healthcare

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“…Prompt recognition and diagnosis of conditions which cause secondary demyelination is crucial since many of these conditions are treatable and reversible. However, the occurrence of these conditions in the elderly poses additional challenges in their management, due to the significant alterations in the capacity of CNS repair mechanisms and other responses to damage [159]. Clinicians should be alert for all aforementioned demyelinating disorders in elderly individuals, since in a significant number of them, such as infections, immediate treatment approaches are required, while in other, such as in demyelination due to pharmaceutical agent administration, changes in a long-term disease management plan may be required.…”

Section: Discussionmentioning

confidence: 99%

Secondary Central Nervous System Demyelinating Disorders in the Elderly: A Narrative Review

et al. 2023

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Secondary demyelinating diseases comprise a wide spectrum group of pathological conditions and may either be attributed to a disorder primarily affecting the neurons or axons, followed by demyelination, or to an underlying condition leading to secondary damage of the myelin sheath. In the elderly, primary demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis, are relatively uncommon. However, secondary causes of CNS demyelination may often occur and in this case, extensive diagnostic workup is usually needed. Infectious, postinfectious, or postvaccinal demyelination may be observed, attributed to age-related alterations of the immune system in this population. Osmotic disturbances and nutritional deficiencies, more commonly observed in the elderly, may lead to conditions such as pontine/extrapontine myelinolysis, Wernicke encephalopathy, and demyelination of the posterior columns of the spinal cord. The prevalence of malignancies is higher in the elderly, sometimes leading to radiation-induced, immunotherapy-related, or paraneoplastic CNS demyelination. This review intends to aid clinical neurologists in broadening their diagnostic approach to secondary CNS demyelinating diseases in the elderly. Common clinical conditions leading to secondary demyelination and their clinical manifestations are summarized here, while the current knowledge of the underlying pathophysiological mechanisms is additionally presented.

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“…This heterogeneity (clinical and biological) is less marked, although also appears in early AD [482,483]. In the 21st century the relevance of previously not well-known brain pathologies (vascular, LBD, TDP-43 (mainly LATE), hippocampal sclerosis, argyrophilic grains), associated with the hallmarks of AD pathology and with other biologic features of aging is notorious (Section 3.2.6) [367,395,420,451,[484][485][486]. The AD physiology is also complex and includes inflammation, neuroimmune disturbances (with activation of microglia), altered glucose, cholesterol and lipid metabolism, oxidative stress, chronic hypoperfusion, mitochondrial and energetic dysfunction, neuronal cell cycle reentry, and extra-brain interactions (Section 3.2.6) [487][488][489].…”

Section: The Unpredictable Futurementioning

confidence: 99%

“…A very old dilemma [30,54] has reemerged based on the evidence that the majority (near three-quarters) of centenarians become demented [506,507]: Is elderly dementia/AD a unique disorder, or is it a matter of the inevitable aging and death? Many scientists argue that aging is the driver, albeit poorly understood, of elderly dementia/AD, (see Section 3.2.6, Figure 6) [367,395,420,451,[484][485][486]503]. For optimistic people, both aging and dementia will be preventable by means of increasing CR and resilience to brain lesions, controlling comorbidities such as inflammation, diabetes, and metabolic disorders, detecting the earliest markers and symptoms of neurodegeneration with innovative diagnostics, and developing multifactorial therapies and precision medicine [496,497,508].…”

Section: The Unpredictable Futurementioning

confidence: 99%

Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History

Bermejo-Pareja,

del Ser

2024

JCM

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Background: The concept of Alzheimer disease (AD)—since its histological discovery by Alzheimer to the present day—has undergone substantial modifications. Methods: We conducted a classical narrative review of this field with a bibliography selection (giving preference to Medline best match). Results: The following subjects are reviewed and discussed: Alzheimer’s discovery, Kraepelin’s creation of a new disease that was a rare condition until the 1970′s, the growing interest and investment in AD as a major killer in a society with a large elderly population in the second half of the 20th century, the consolidation of the AD clinicopathological model, and the modern AD nosology based on the dominant amyloid hypothesis among many others. In the 21st century, the development of AD biomarkers has supported a novel biological definition of AD, although the proposed therapies have failed to cure this disease. The incidence of dementia/AD has shown a decrease in affluent countries (possibly due to control of risk factors), and mixed dementia has been established as the most frequent etiology in the oldest old. Conclusions: The current concept of AD lacks unanimity. Many hypotheses attempt to explain its complex physiopathology entwined with aging, and the dominant amyloid cascade has yielded poor therapeutic results. The reduction in the incidence of dementia/AD appears promising but it should be confirmed in the future. A reevaluation of the AD concept is also necessary.

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CNS Ageing in Health and Neurodegenerative Disorders

Cited by 15 publications

References 139 publications

The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis

The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis

Secondary Central Nervous System Demyelinating Disorders in the Elderly: A Narrative Review

Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History

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