Liduin Souren

Evidence and mechanisms of retrogenesis in Alzheimer's and other dementias: Management and treatment import

Retrogenesis is the process by which degenerative mechanisms reverse the order of acquisition in normal development. Alzheimers disease (AD) and related conditions in the senium have long been noted to resemble “a return to childhood.” Previously, we noted that the functional stages of AD precisely and remarkably recapitulated the acquisition of the same functional landmarks in normal human development. Subsequent work indicated that this developmental recapitulation also applied to the cognitive and related symptoms in AD. Remarkably, further investigations revealed that the same neurologic “infantile” reflexes, which mark the emergence from infancy in normal development, are equally robust indicators of corresponding stages in AD. Neuropathologic and biomolecular mechanisms for these retrogenic processes are now evident. For example, the pattern of myelin loss in AD appears to mirror the pattern of myelin acquisition in normal development. Also, recent findings indicate that mitogenic factors become reactivated in AD, and, consequently, the most actively “growing” brain regions are the most vulnerable. Because of this robust retrogenic process, the stages of AD can be translated into corresponding developmental ages (DAs). These DAs can account for the overall management and care needs of AD patients. A science of AD management can be formulated on the basis of the DA of the Alzheimers patient, taking into consideration differences of AD from normal development as well as homologies.

Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer's and other dementing processes.

Abstract Data from clinical, electrophysiologic, neurophysiologic, neuroimaging and neuropathologic sources indicates that the progression of brain aging and Alzheimer’s disease (AD) deterioration proceeds inversely to human ontogenic acquisition patterns. A word for this process of degenerative developmental recapitulation, “retrogenesis”, has been proposed. These retrogenic processes provide new insights into the pathologic mechanism of AD deterioration. An understanding of retrogenic phenonmena can also result in insights into the applicability of retrogenic pathologic mechanisms for non-AD dementing disorders. Management strategies based upon retrogenesis have recently been proposed. Retrogenic pathophysiology also points to previously unexplored pharmacologic approaches to dementia prevention and treatment.

Equilibrium and Limb Coordination in Mild Cognitive Impairment and Mild Alzheimer's Disease

OBJECTIVE: To examine changes in equilibrium and limb coordination in normal aging, mild cognitive impairment, and moderate cognitive impairment associated with early probable Alzheimers disease (AD), by means of parametric clinical measures.

Contractures and Loss of Function in Patients with Alzheimer's Disease

OBJECTIVE: To investigate the prevalence of contractures in patients with Alzheimers disease and to assess possible associations between contractures and cognitive and functional decline in Alzheimers disease.

Neuromotor Changes in Alzheimer's Disease: Implications for Patient Care

As a result of the neuropathologic process of Alzheimers disease (AD), significant changes occur in neuromotor function (e.g., paratonia and compulsive grasping). These changes become manifest in the moderately severe stage of AD, when patients begin to require ongoing assistance with activities of daily life (ADL), and they are prominent in the severe stage of AD, when patients are continuously dependent on a caregiver. Patients in these stages often display behavioral disturbances during care activities. These disturbing behaviors result not only from cognitive impairment, but also from a patients physical inability to cooperate with the caregiver. When care management strategies take into account the characteristic physical restrictions resulting from the neuromotor changes that accompany advanced AD, the caregiving process may be significantly facilitated.

Overview of methodologic issues for pharmacologic trials in mild, moderate, and severe Alzheimer's disease.

To address the issue of mild, moderate, and severe Alzheimers disease (AD), it is necessary to initially establish some agreement on terminology. In recent decades, these terms have frequently been defined using screening instrument scores with measures such as the Mini-Mental State Examination (MMSE). There are many problems with this approach, perhaps the most salient of which is that it has contributed to the total and tragic neglect of patients with severe AD. An alternative approach to the classification of AD severity is staging. This approach has advanced to the point where moderately severe and severe AD can be described in detail. Procedures for describing this previously neglected latter portion of AD have recently been extensively validated. Staging is also uniquely useful at the other end of the severity spectrum, in differentiating early aging brain/behavior changes, incipient AD, and mild AD. Temporally, with staging procedures, it is possible to track the course of AD approximately three times more accurately than with the MMSE. The net result of the advances in AD delineation is that issues such as prophylaxis, modification of course, treatment of behavioral disturbances, loss of ambulation, progressive rigidity, and the development of contractures in AD patients can now be addressed in a scientifically meaningful way that will hopefully bestow much benefit in AD patients and those who care for them.

Progression of Alzheimer’s disease: variability and consistency: ontogenic models, their applicability and relevance

Much has been learned about the clinical symptomatology of Alzheimers disease (AD) and ontogenic reciprocal relationships in the past few decades. It is now possible to describe and verify inexorable symptomatic sequences and corresponding temporal relationships. It is also possible to identify more variable symptoms in AD. Ontogenic models can be useful in providing a clearer understanding of the nature of AD symptomatology in terms of both consistency and variability. These models can also be informative in explicating the management needs of AD patients and the treatment possibilities of AD symptoms as well as the etiology of variability in AD symptoms.

Utility of developmental reflexes in the differential diagnosis and prognosis of incontinence in Alzheimer's disease

Four developmental reflexes, the tactile suck reflex, the palmar and plantar grasp reflexes, and the plantar extensor reflex, were examined in 784 individuals, including healthy elderly, cognitively and functionally mildly impaired individuals, and patients with Alzheimers disease (AD) in all stages of clinical severity. The study population was classified into six categories of increasingly impaired functional performance, and prevalence of the four individual reflexes and of a summary reflex measure, consisting of a combination of these four reflexes, was determined for each category. Prevalence of all five reflex measures was more than six times higher for those categories that comprised only permanently doubly incontinent patients as compared to those categories that comprised only continent individuals (P < .001). Frequency of developmental reflexes rose sharply with the onset of progressive incontinence. Since the return of these reflexes in AD is associated with severe cortical dysfunction, it is concluded that these developmental reflexes are useful in differentiating incontinence of cortical origin from incontinence resulting from potentially reversible causes.