Cognitive decline and Alzheimer’s disease
Claude Leray in Dietary Lipids for Healthy Brain Function, 2017
MCI progresses to dementia frequently. The clinical situation is then characterized by significant cognitive deficits, severe enough to affect family, social, or professional life. Thus, a progressive loss of memory is recorded, but also an alteration in motor movements and language and difficulties with thinking or problem-solving. The disease has been associated specifically with a loss of executive functions that characterize the execution of tasks requiring a goal or defined objectives. These high-level functions are involved in many forms of cognitive activities (Section 7.9). Among dementias, a distinction should be made between Alzheimer’s disease, frontotemporal dementia (Pick’s disease), vascular dementia, and other dementia associated with certain diseases (Creutzfeld–Jacob, Parkinson, Huntington). Certain neurologists even argue that the majority of dementia in the elderly would be a trouble combining degenerative disease and vascular pathology. The term “senile dementia” was used when it was thought that memory loss and confusion were a normal part of aging. It is more common now to refer to dementia, or early-onset dementia, if the person is under 65 years old. As Prof. Roger Gil (2010) said: “It is difficult to have an unitary approach of a set as disparate as organic dementia. This disparity is due to the symptomatology of dementia syndrome that is not one but is plural; it also lies in the diversity of all etiologies as well as to the heterogeneity of clinical presentations within a same etiology.”Thus, in the absence of reliable biomarkers, clinicians must unfortunately wait for the full establishment of the disease before characterizing with success an advanced dementia, a time that can delay any intervention. Following the works of Prof. Bruno Dubois, Pierre and Marie Curie University in Paris, the current trend is to clinically characterize an Alzheimer’s prodromal phase after a preclinical phase, a period still currently poorly characterized that lasts from 15 to 20 years. The prodromal stage shows symptoms including impairment of episodic memory of the hippocampal type that does not yet alter daily life and the presence of biomarkers detected in the cerebrospinal fluid (β-amyloid peptide) or by MRI (hippocampal atrophy, senile plaques). The “World Alzheimer Report” estimated that in 2010 the number of people affected in the world by dementia was 35.6 million and will reach 66 million in 2030 and more than 115 million by 2050 if no medical treatment reduces the incidence of this disease. Globally, the costs incurred by dementia have been estimated at more than US$600 billion dollars. The US Alzheimer’s Association has estimated that more than 5 million Americans are living with Alzheimer’s disease, with approximately 200,000 individuals being under 65 years. Notably, one in three seniors dies with Alzheimer’s or another dementia. In 2015, the cost of the unpaid care for patients has an estimated economic value of more than US$220 billion.
Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
The duration of the disease varies from 1 to 10 or more years. The principal lesions are widespread loss of neurons distributed diffusely and symmetrically throughout the cerebral cortex, amyloid plaques, neurofibrillary tangles, and neuroaxonal degeneration (Plate 2). The involvement of the basal ganglia and other subcortical structures is minimal. In cortical degeneration, the disorder starts with focal alterations of neurites followed by a phagocytic response. Later amyloid protein plaques are deposited and surrounded by few macrophages with swollen neurites containing secondary lysosomes. Amyloid plaques are found in almost all elderly patients, but their number is great only when signs of clinical dementia are apparent and neuronal fallout is detectable. Patchy lesions in the white matter in aging brain and dementia have also been reported. The presence of abnormal proteins characterizes the manifestation of the Alzheimer’s disease, although its direct cause is still unknown. The deposition of abnormal proteins in the amyloid plaques is found concentrated near old infarcts and their presence probably represents nonspecific degenerative reactions to the causative agent by focal or individual cortical neurons. The primary cause may be associated with slowly progressing deterioration of protein synthesis by the endoplasmic reticulum (Nissl substance); its elimination is partly controlled by the production of secondary lysosomes. Recent publications suggest that various etiological factors are responsible for senile dementia. The neuritic or senile plaques in Alzheimer’s disease consist of a dense core of extracellular amyloid surrounded by enlarged neurites containing degenerating mitochondria and lamellar lysosomes with increased hydrolase activity. Neurotransmitter substances, such as dopamine and norepinephrine, and the gabanergic system show significant losses with age, but there are no specific changes in Alzheimer dementia. Monoamine oxidase activity is increased in the brain in Alzheimer’s disease, and the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid are decreased. Changes in the cholinergic system seem to be related, and choline acetyltransferase activity is reduced and acetylcholine increased in certain cortical areas in Alzheimer’s disease and related disorders. Aluminum concentrations are increased in some brain regions of the brain in Alzheimer’s disease 10 to 30 times the normal average concentrations. Since aluminum exhibits cytotoxicity, this metal has been implicated in the pathogenesis of several degenerative processes in the human central nervous system. In some cases, the presence of aluminum in the abnormal tissue may be the consequence of the deteriorated metabolic control. So matotoxin receptors showed reduced numbers in the cerebral cortex in Alzheimer’s disease; vasopressin and oxitocin neurons are modified with aging and in senile dementia. There is a certain relationship between Down’s syndrome and Alzheimer’s disease. Down’s patients as middle-aged adults often become demented and die of a particularly aggressive form of Alzheimer’s disease.
Nutrition in Neurodegenerative Disorders and Cognitive Impairment
David Heber, Zhaoping Li in Primary Care Nutrition, 2017
Dementia includes symptoms of memory loss, changes in mood and behavior, and problems with communication, reasoning, and the ability to carry out daily activities. A diagnosis of dementia requires substantial impairment to be present in one or more cognitive domains. The impairment must be sufficient to interfere with independence in everyday activities. The diagnosis of mild neurocognitive disorder or MCI is made when there is modest impairment in one or more cognitive domains. The individual is still independent in everyday activities, albeit with greater effort. The impairment must represent a decline from a previously higher level and should be documented both by history and by objective assessment. Further, the cognitive deficits must not occur exclusively in the context of a delirium or be better explained by another mental disorder. A full discussion of the differential diagnosis of dementias and MCI is beyond the scope of this chapter. However, primary care providers working with specialized memory clinics can diagnose the syndromes of dementia and MCI. The diagnosis is based on history, examination, and objective assessments, using standard criteria established by the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (Table 16.1) (American Psychiatric Association 2013). Dementia is associated with diseases causing structural and chemical changes in the brain.
Deprescribing: a challenge for clinical cardiologists
Published in Acta Cardiologica, 2020
Deprescribing is a holistic process to identify medications that can be ceased, substituted or reduced. This process can improve the health of older patients and also enhance their compliance to the prescribed medications which are actually beneficial. Recommendations and guidelines have been elaborated for extensively prescribed drugs. In clinical cardiology the process of deprescribing is a challenge for doctors because of withdrawal-related adverse effects, but it may be applied in certain clinical conditions such as the discontinuation of statin prescription in patients with advanced senile dementia and those with limited life expectancy. Deprescribing is also focussed on the scarcely known effects of prolonged therapy after the acute phase of a disease is over, especially when continuation may signify potential life-long treatment. There needs to be collaboration between the consultant cardiologist who first prescribes medications and family doctors who are responsible for the long-term care of the patient and reviewing prescribed medications may be necessary.
Disorders of Everyday Actions in Subjects Suffering from Senile Dementia of Alzheimer's Type: An Analysis of Dressing Performance
Published in Neuropsychological Rehabilitation, 1999
Dressing ability was studied in 25 subjects suffering from senile dementia of Alzheimer's type (SDAT). Performance was assessed by means of the Action Coding System of Schwartz et al. (1991, 1995) and a modified version of Optimage (Gendron & Lévesque, 1993). Results showed that impairments of dressing ability were common in SDAT. Global measures of performance were found to correlate with severity of dementia as measured by the Reisberg, Ferris, DeLeon, and Crook (1982) Global Deterioration Scale and the Mini Mental State Examination. More detailed analyses showed that errors were more frequent in fastening than in the other components of the sequence (selecting, orienting, putting on, and adjusting pieces of clothes). In mildly impaired subjects, the most common errors were incorrect choices of clothing and unsatisfactory executions of basic action units, whereas in more severely impaired subjects, other kinds of error also occurred, mostly passivity. Methodological implications of these results are drawn for further cognitive analysis of everyday actions in SDAT.
Diagnosis of Senile Dementia Alzheimer's Type
Published in Clinical Gerontologist, 1984
Diagnosis of senile dementia Alzheimer-type (SDAT) poses a serious challenge because the symptoms of the disease may vary widely, the early stages may be undetectable, other reversible forms of dementia may mimic SDAT, and only histopathological examination may confirm the presence of the disease. The incurability of the disease and assumptions that senility is a normal part of aging may add to a dismissive approach to the disease. A review of recent medical literature attests to professional awareness of inaccuracies and imprecision in diagnosing senile dementia and of the need for more comprehensive diagnostic evaluation. The literature is difficult to integrate however because of terminological confusion, the different levels of specificity at which the disease is discussed and the fundamental ambiguity of the disease.