Mild cognitive impairment in amyotrophic lateral sclerosis: current view.

Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms.

Behavioral disorders in Parkinson disease: current view.

Patients with Parkinson disease (PD) frequently experience several behavioral symptoms, such as anxiety, apathy, irritability, agitation, impulsive control and obsessive-compulsive or REM sleep behavior disorders, which can cause severe psychosocial problems and impair quality of life. Occurring in 30-70% of PD patients, these symptoms can manifest at early stages of the disease, sometimes even before the appearance of classic motor symptoms, while others can develop later. Behavioral changes in PD show distinct patterns of brain atrophy, dopaminergic and serotonergic deterioration, altered neuronal connectivity in frontostriatal, corticolimbic, default mode and other networks due to a cascade linking molecular pathologies and deficits in multiple behavior domains.

Behavioral disorders in dementia with Lewy bodies: old and new knowledge.

Dementia with Lewy bodies (DLB), the second most common primary degenerative neurocognitive disorder after Alzheimer disease, is frequently preceded by REM sleep behavior disorders (RBD) and other behavioral symptoms, like anxiety, irritability, agitation or apathy, as well as visual hallucinations and delusions, most of which occurring in 40-60% of DLB patients. Other frequent behavioral symptoms like attention deficits contribute to cognitive impairment, while attention-deficit/hyperactivity disorder (ADHD) is a risk factor for DLB. Behavioral problems in DLB are more frequent, more severe and appear earlier than in other neurodegenerative diseases and, together with other neuropsychiatric symptoms, contribute to impairment of quality of life of the patients, but their pathophysiology is poorly understood.

The Pathobiology of Behavioral Changes in Multiple System Atrophy: An Update.

While cognitive impairment, which was previously considered a red flag against the clinical diagnosis of multiple system atrophy (MSA), is a common symptom of this rare neurodegenerative disorder, behavioral disorders are reported in 30 to 70% of MSA patients. They include anxiety, apathy, impaired attention, compulsive and REM sleep behavior disorders (RBD), and these conditions, like depression, are early and pervasive features in MSA, which may contribute to disease progression. Despite changing concepts of behavioral changes in this synucleinopathy, the underlying pathophysiological and biochemical mechanisms are poorly understood.

Pathomechanisms of behavioral abnormalities in Huntington disease: an update.

Huntington disease (HD), a devastating autosomal-dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat, is clinically characterized by a triad of symptoms including involuntary motions, behavior problems and cognitive deficits. Behavioral symptoms with anxiety, irritability, obsessive-compulsive behaviors, apathy and other neuropsychiatric symptoms, occurring in over 50% of HD patients are important features of this disease and contribute to impairment of quality of life, but their pathophysiology is poorly understood. Behavior problems, more frequent than depression, can be manifest before obvious motor symptoms and occur across all HD stages, usually correlated with duration of illness.

Depression and anxiety in multiple sclerosis. Review of a fatal combination.

Depression and anxiety are the most frequent neuropsychiatric symptoms of multiple sclerosis (MS), an autoimmune-mediated demyelinating neurodegenerative disease. Their prevalence is 25-65% and 20-54%, respectively, often associated with chronic fatigue and cognitive impairment, but usually not correlated with motor and other deficits, suggesting different pathophysiological mechanisms. Both disorders often arise before MS diagnosis, lead to faster disability and impair the quality of life.

Mild cognitive impairment in Huntington's disease: challenges and outlooks.

Although Huntington's disease (HD) has classically been viewed as an autosomal-dominant inherited neurodegenerative motor disorder, cognitive and/or behavioral changes are predominant and often an early manifestation of disease. About 40% of individuals in the presymptomatic period of HD meet the criteria for mild cognitive impairment, later progressing to dementia. The heterogenous spectrum of cognitive decline is characterized by deficits across multiple domains, particularly executive dysfunctions, but the underlying pathogenic mechanisms are still poorly understood.

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks.

Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions.

Understanding depression with amyotrophic lateral sclerosis: a short assessment of facts and perceptions.

Depression with an average prevalence of 25-40% is a serious condition in amyotrophic lateral sclerosis (ALS) that can impact quality of life and survival of patients and caregiver burden, yet the underlying neurobiology is poorly understood. Preexisting depression has been associated with a higher risk of developing ALS, while people with ALS have a significantly higher risk of developing depression that can cause multiple complications. Depression may be a prodromal or subclinical symptom prior to motor involvement, although its relations with disease progression and impairment of quality of life are under discussion.

The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update.

Cognitive dysfunction is an important non-motor symptom in amyotrophic lateral sclerosis (ALS) that has a negative impact on survival and caregiver burden. It shows a wide spectrum ranging from subjective cognitive decline to frontotemporal dementia (FTD) and covers various cognitive domains, mainly executive/attention, language and verbal memory deficits. The frequency of cognitive impairment across the different ALS phenotypes ranges from 30% to 75%, with up to 45% fulfilling the criteria of FTD.

Advances in Molecular Medicine: Unravelling Disease Complexity and Pioneering Precision Healthcare.

The escalating impacts of the climate crisis, zoonotic spill-over, and antibiotic resistance have positioned molecular medicine at the forefront of pioneering translational research [...

Pathomechanisms of cognitive and behavioral impairment in corticobasal degeneration.

Corticobasal degeneration (CBD) is a rare, sporadic, late-onset progressive neurodegenerative disorder of unknown etiology, clinically characterized by an akinetic-rigid syndrome, behavior and personality disorders, language problems (aphasias), apraxia, executive and cognitive abnormalities and limb dystonia. The syndrome is not specific, as clinical features of pathologically proven CBD include several phenotypes. This 4-repeat (4R) tauopathy is morphologically featured by often asymmetric frontoparietal atrophy, ballooned/achromatic neurons containing filamentous 4R-tau aggregates in cortex and striatum, thread-like processes that are more widespread than in progressive supranuclear palsy (PSP), pathognomonic "astroglial plaques", and numerous inclusions in both astrocytes and oligodendroglia ("coiled bodies") in the white matter.

Mild cognitive impairment in multiple system atrophy: a brain network disorder.

Cognitive impairment (CI), previously considered as a non-supporting feature of multiple system atrophy (MSA), according to the second consensus criteria, is not uncommon in this neurodegenerative disorder that is clinically characterized by a variable combination of autonomic failure, levodopa-unresponsive parkinsonism, motor and cerebellar signs. Mild cognitive impairment (MCI), a risk factor for dementia, has been reported in up to 44% of MSA patients, with predominant impairment of executive functions/attention, visuospatial and verbal deficits, and a variety of non-cognitive and neuropsychiatric symptoms. Despite changing concept of CI in this synucleinopathy, the underlying pathophysiological mechanisms remain controversial.

Mild cognitive impairment in dementia with Lewy bodies: an update and outlook.

Dementia with Lewy bodies (DLB), the second most common degenerative neurocognitive disorder after Alzheimer disease (AD), is frequently preceded by a period of mild cognitive impairment (MCI), in which cognitive decline is associated with impairment of executive functions/attention, visuospatial deficits, or other cognitive domains and a variety of noncognitive and neuropsychiatric symptoms, many of which are similar but less severe than in prodromal AD. While 36-38% remain in the MCI state, at least the same will convert to dementia. Biomarkers are slowing of the EEG rhythms, atrophy of hippocampus and nucleus basalis of Meynert, temporoparietal hypoperfusion, signs of degeneration of the nigrostriatal dopaminergic, cholinergic and other neurotransmitter systems, and inflammation.

Depression in dementia with Lewy bodies: a critical update.

Depression with an estimated prevalence of 35% is a frequent manifestation of dementia with Lewy bodies (DLB), having negative effects on cognitive performance and life expectancy, yet the underlying neurobiology is poorly understood and most likely heterogeneous. Depressive symptoms in DLB can occur during the clinical course and, together with apathy, is a common prodromal neuropsychiatric symptom of this neurocognitive disorder in the group of Lewy body synucleinopathies. There are no essential differences in the frequency of depression in DLB and Parkinson disease-dementia (PDD), while its severity is up to twice as high as in Alzheimer disease (AD).

Morphological characteristics differentiate dementia with Lewy bodies from Parkinson disease with and without dementia.

Dementia with Lewy bodies (DLB) and Parkinson disease (PD) with and without dementia are entities of a spectrum of Lewy body diseases. About 26.3% of all PD patients develop dementia increasing up to 83%.

The heterogeneity of late-life depression and its pathobiology: a brain network dysfunction disorder.

Depression is frequent in older individuals and is often associated with cognitive impairment and increasing risk of subsequent dementia. Late-life depression (LLD) has a negative impact on quality of life, yet the underlying pathobiology is still poorly understood. It is characterized by considerable heterogeneity in clinical manifestation, genetics, brain morphology, and function.

Pathomechanisms of depression in progressive supranuclear palsy.

Depression is one of the most frequent neuropsychiatric symptoms in progressive supranuclear palsy (PSP), a four-repeat tauopathy and most common atypical parkinsonian disorder, but its pathophysiology and pathogenesis are poorly understood. Pubmed/Medline was systematically analyzed until January 2023, with focus on the prevalence, major clinical features, neuroimaging findings and treatment options of depression in PSP. The average prevalence of depression in PSP is around 50%; it does usually not correlate with most other clinical parameters.

Pathomechanisms of cognitive impairment in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by early postural instability and falls, oculomotor dysfunction (vertical supranuclear gaze palsy), parkinsonism with poor response to levodopa, pseudobulbar palsy, and cognitive impairment. This four-repeat tauopathy is morphologically featured by accumulation of tau protein in neurons and glia causing neuronal loss and gliosis in the extrapyramidal system associated with cortical atrophy and white matter lesions. Cognitive impairment being frequent in PSP and more severe than in multiple system atrophy and Parkinson disease, is dominated by executive dysfunction, with milder difficulties in memory, and visuo-spatial and naming dysfunctions.