“GR.T.POPA” UNIVERSITY OF MEDICINE AND PHARMACY IAȘI
NEW YORK UNIVERSITY AGING AND DEMENTIA RESEARCH CENTER
THE CONCEPT OF RETROGENESIS: NEW WAYS OF UNDERSTANDING
ALZHEIMER’S DISEASE
PhD Thesis Abstract
PhD Supervisors:
PROFESSOR VASILE ASTĂRĂSTOAE
PROFESSOR BARRY REISBERG
PhD Student:
LIANA RADA BORZA, MD, BSc Hons
2012
Keywords: Alzheimer’s disease, retrogenesis, electroencephalographic activity,
gray matter, elder abuse, social protection
TABLE OF CONTENTS
I. THE CONCEPT OF RETROGENESIS – CURRENT STATE OF KNOWLEDGE
I.1 JUSTIFICATION OF THE TOPIC
I.2 HISTORICAL BACKGROUND
I.3 DEFINITION OF RETROGENESIS
I.4 FUNCTIONAL/CLINICAL RETROGENESIS
I.5 COGNITIVE RETROGENESIS
I.6 EMOTIONAL RETROGENESIS
I.7 NEUROLOGIC RETROGENESIS
I.8 NEUROPATHOLOGIC RETROGENESIS
I.9 NEUROMETABOLIC EVIDENCE FOR RETROGENESIS
I.10 EVIDENCE FROM TAU PHOSPHORYLATION
I.11 A SCIENCE OF ALZHEIMER’S DISEASE CARE BASED ON RETROGENESIS
II. ELECTROENCEPHALOGRAPHIC EVIDENCE FOR RETROGENESIS
II.1 INTRODUCTION TO THE ROLE OF ELECTROENCEPHALOGRAPHY
IN ALZHEIMER’S DISEASE
II.2 OBJECTIVE
II.3 MATERIALS AND METHODS
II.4 RESULTS
II.5 CONCLUSIONS
III. EVIDENCE FOR RETROGENESIS FROM GRAY MATTER & CEREBRAL
REGIONS/HEMISPHERES DEVELOPMENT & DEGENERATION
III.1 OBJECTIVE
III.2 MATERIALS AND METHODS
III.3 RESULTS
III.4 CONCLUSIONS
IV. A RETROGENIC MODEL FOR DETECTING ABUSE OF INSTITUTIONALIZED
PEOPLE WITH ALZHEIMER’S DISEASE
IV.1 INTRODUCTION TO ELDER ABUSE
IV.2 OBJECTIVE
IV.3 MATERIALS AND METHODS
IV.4 RESULTS
IV.5 DISCUSSION
V. ETHICAL AND FORENSIC IMPLICATIONS OF RETROGENESIS
V.1 OBJECTIVE
V.2 MATERIALS AND METHODS
V.3 RESULTS
V.4 DISCUSSION
VI. FINAL CONCLUSIONS & THESIS CONTRIBUTIONS
REFERENCES
APPENDICES 1 – 10
ACKNOWLEDGEMENTS
I. THE CONCEPT OF RETROGENESIS – CURRENT STATE OF KNOWLEDGE
I.1. JUSTIFICATION OF THE TOPIC
The topic chosen to be studied is one of great interest, if we take into consideration the fact
that the increase in the absolute and relative number of elderly people will be accompanied by
a significant rise of the number of people with Alzheimer’s disease (AD). The estimated
number of people with dementia worldwide is 24.3 million, with 4.6 million new cases of
dementia every year (about one new case every 7 seconds). The number of people living with
dementia will almost double every 20 years, to 42.3 million in 2020 and 81.1 million in 2040
[40]. In this regard, it would be necessary to explore new ways of understanding AD, which
may help us to improve the management of this growing medical, social and economic
problem.
I.2. HISTORICAL BACKGROUND
General relationships between aging and development have long been noted by poets and
playwrights. Aristophanes (423 B.C.) noted in his play “The Clouds” that “old men are
children twice over”. In Shakespeare’s comedy “As you like it”, Jacque’s “All the world’s a
stage” soliloquy concludes that the “Last scene of all, That ends this strange, eventful
history/Is second childishness…” [122, 125] More than two centuries ago, physicians also
began to note similarities between AD and normal development, as follows: “I met with an
instance of a woman between 80 and 90 who exhibited the marks of a second infancy, by such
a total decay of her mental faculties as to lose all consciousness in discharging her alvine and
urinary excretions.” (Benjamin Rush, 1793) [118, 122, 125] In the 1960s and 1970s, de
Ajuriaguerra and his associates observed that the decline of certain capacities in dementia
appeared to reverse Piaget’s developmental stages [122, 125].
I.3. DEFINITION OF RETROGENESIS
Retrogenesis has been defined by Reisberg and collaborators as the process by which the
degenerative mechanisms from AD inversely recapitulate the processes of the normal
neurodevelopment [121, 122].
I.4. FUNCTIONAL/CLINICAL RETROGENESIS
The Functional Assessment Staging (FAST) procedure describes a total of 16 successive
functional stages and substages in the continuum from normal aging to the late phase of AD
[110, 118]. The clinical retrogenic pattern in AD is most clearly described with the FAST
staging procedure, as the sequence of functional loss outlined with the FAST appears to be a
precise reversal of the order of acquisition of the same functions in the course of normal
human development. It has also been noted that each FAST stage in AD can be described in
terms of a corresponding developmental age (DA) (see Table 1.3) [110, 121, 123, 124, 125,
127].
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I.5. COGNITIVE RETROGENESIS
It was reported that the use of the adapted and modified Ordinal Scales of Psychological
Development (OPSD), originally developed by Uzgiris & Hunt (1975) for cognitive testing in
infants, has proved to be superior to the application of traditional tests, such as the Mini-
Mental State Examination (MMSE), in assessing the residual cognitive capacity of subjects
with moderately severe and severe AD [7, 145]. Childhood intelligence test measures, such as
the Tanaka-Binet intelligence scale (the Japanese version of the Binet scale), also proved to be
useful in assessing cognition in moderate to severe AD subjects [147]. Conversely, it was
demonstrated that the MMSE, a standard AD measurement, is a suitable instrument for
screening higher mental function in children at the age of 4 years and above [99].
I.6. EMOTIONAL RETROGENESIS
The emotional and behavioral changes in the person with AD are frequently similar to those
experienced by infants and children at corresponding DAs [125]. For instance, it was noted
that a stage 6 AD person who is frustrated or mistreated will respond with verbal and physical
outbursts, just as a 2- to 5-year-old child will respond with temper tantrums [113, 123, 125].
I.7. NEUROLOGIC RETROGENESIS
It was observed that developmental reflexes (synonyms: infantile, neonatal or primitive
reflexes) reappear in the AD person. Studies indicated that developmental reflexes emerge in
AD at a point which might be anticipated from the corresponding DA and appear to be just as
robust markers of the degenerative course of AD as of normal human development [43, 44,
45, 46, 110, 123]. It was also noted that the emergence and increase of paratonia in AD can, to
some extent, be considered as the return of an infantile stabilization reflex mechanism, which
parallels the patient’s decline in motor performance [151].
I.8. NEUROPATHOLOGIC RETROGENESIS
It was indicated that the brain areas which are myelinated early in life become increasingly
more thickly myelinated as time progresses, while the most recently myelinated ones have the
least myelin deposition [122]. Consequently, the developmentally most recent, thinly
myelinated, brain regions are the most vulnerable to AD pathology [123].
I.9. NEUROMETABOLIC EVIDENCE FOR RETROGENESIS
A leading investigator in neurometabolism noted the similarities between the pattern of
neurometabolism in normal infant brain and the pattern of neurometabolic deficit in late-stage
AD brain [101, 102]. It was also found that the regions of the brain which were most
metabolically active in the default (awake, resting) states in young adults were the most
vulnerable to the AD pathology [19].
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I.10. EVIDENCE FROM TAU PHOSPHORYLATION
It was observed that the extent and the sites of phosphorylation in tau from human fetal brains
and tau from paired helical filaments in AD brains are similar, which suggests that the
abnormal phosphorylation of tau in AD may be the result of reactivation of pathways
governing the phosphorylation of tau in the developing brain [18, 72].
I.11. A SCIENCE OF ALZHEIMER’S DISEASE CARE BASED ON RETROGENESIS
An understanding of the retrogenic process in AD also provides the basis for a detailed
management science. This new science of AD care can be formulated into axioms, postulates
and caveats. The care axioms are self-evident basic human needs and desires, such as those
for dignity, accomplishment, social acceptance, love and movement, applicable to all human
beings and to AD patients at all stages. The postulates are testable hypotheses of AD patient
care based on the DA-retrogenesis model. Finally, the caveats are exceptions to the DA-
retrogenesis model, based on the nature of human aging and AD [122, 124].
II. ELECTROENCEPHALOGRAPHIC EVIDENCE FOR RETROGENESIS
II.1. INTRODUCTION TO THE ROLE OF ELECTROENCEPHALOGRAPHY IN
ALZHEIMER’S DISEASE
It was revealed an important diagnostic value of electroencephalography (EEG) in the
estimation of the severity of AD parallel to psychometric scales [74]. It seems that EEG could
be a predictor of the progression of AD [67, 74]. Further data implicate EEG as a potential
tool for differential diagnosis of AD from various dementing illnesses [67]. Furthermore,
studies reported that flicker at 10 Hz (a frequency near to the peak power of endogenous
alpha) can enhance recognition memory by eliciting alpha-like EEG activity [173, 174].
II.2. OBJECTIVE
The objective of this study is to examine electroencephalographic (EEG) patterns in relation
to the retrogenesis process in AD.
II.3. MATERIALS AND METHODS
The present study has been performed as a qualitative meta-analysis including 30 original
papers from the scientific literature, which were published between 1949 and 2008 [12, 13,
24, 25, 27, 33, 36, 39, 48, 50, 51, 59, 61, 63, 68, 71, 76, 83, 85, 95, 98, 100, 104, 107, 108,
133, 144, 150, 158, 171]. Thus, there were initially included 57 papers, but then there were
excluded 27 articles that did not clearly describe the EEG activity patterns in AD stages or the
EEG activity patterns in the corresponding developmental age groups. This meta-analysis is a
qualitative one because it is based on nominal data expressing the gradual decrease or
increase of delta, theta, alpha and beta wave activity. The data have been extracted from the
publications and expressed in a standard format. SPSS 16.0 was used to conduct this analysis.
As the nominal data are also categorical, contingency tables or crosstabs have been created
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first. In order to compare delta, theta, alpha and beta activity between the developmental age
groups and the AD stages, the Chi square test have been applied.
II.4. RESULTS
Overall, the papers included in this analysis show that the hallmark of EEG abnormalities in
AD patients is a shift from fast to slow wave activity, with the most marked increase of delta
activity not occurring until severe AD, while in normal development there is a continuum of
increase from delta frequency in the youngest age group to beta frequency in older
individuals. Specifically, it was found that there is no statistically significant difference
(p>0.05) in delta, theta, alpha and beta activity between the 4 stages of AD and their
corresponding age groups in normal development (see the data marked in red in Table 2.1).
Table 2.1. The comparison of delta, theta, alpha and beta activity between the developmental age
groups and the AD stages
NS = not significant; SS = statistically significant
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II.5. CONCLUSIONS
This work defines in detail an EEG retrogenic model showing that the EEG activity patterns
in AD inversely recapitulate the patterns in normal development. Such a model could be
relevant for a better understanding of the nature of AD. A further implication of the findings
of the present study is that EEG might be useful as a routine examination for AD patients.
III. EVIDENCE FOR RETROGENESIS FROM GRAY MATTER & CEREBRAL
REGIONS/HEMISPHERES DEVELOPMENT & DEGENERATION
III.1. OBJECTIVE
The objective of the present work is to examine the patterns of gray matter (GM) and cerebral
regions/hemispheres development or degeneration in relation with the process of retrogenesis
from AD.
III.2. MATERIALS AND METHODS
The present study has been performed as a systematic review, including 19 original papers
that, except one, represent volumetric studies based on MRI scanning, which were published
between 1996 – 2009 and were selected from the PubMed database [5, 10, 21, 52-54, 65, 84,
97, 135, 140, 143, 152-156, 164, 165]; specific selection criteria were: (1) articles reporting
data on the development of GM and cerebral regions/hemispheres in normal children,
adolescents and adults; and (2) articles reporting data on the degeneration of GM and the
same regions/hemispheres in subjects who were in different stages of AD. Two reviewers
independently selected the potentially eligible studies based on titles and abstracts. The
studies included in the present systematic review have done well on the following criteria for
quality assessment: objectives, study population, study design, comparison group, follow-up,
and analysis and data presentation [15, 78].
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III.3. RESULTS
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III.4. CONCLUSIONS
The present systematic review demonstrates that the regional GM atrophy sequence in AD is
the reverse of the GM normal developmental sequence. This review also emphasizes that
cortical regions that mature earliest in infancy tend to degenerate last in AD (e.g. the
sensorimotor cortices). In addition, the cortical regions that normally develop last are the first
to degenerate in AD (e.g. the temporal regions). Furthermore, it is indicated that the
hemispheric asymmetry (left-to-right) in AD reverses the one in normal development (right-
to-left).
IV. A RETROGENIC MODEL FOR DETECTING ABUSE OF
INSTITUTIONALIZED PEOPLE WITH ALZHEIMER’S DISEASE
IV.1. INTRODUCTION TO ELDER ABUSE
Elder maltreatment is not a new phenomenon, but it has been recently recognized as a
widespread and possibly growing social problem [26, 81]. Statutory definitions of elder abuse
may include physical abuse, psychological or emotional abuse, sexual abuse, financial
exploitation, neglect, abandonment, and even self-neglect [3]. Compared with incidents of
abuse of women and children, elder abuse has received little attention [89]. Caregiver burden
is among the most cited explanations for elder abuse in the literature [47]. Increasingly,
institutionalization is seen as a risk factor for elder abuse and neglect [26, 80]. It was thus
suggested that an instrument to accurately assess elder abuse in long-term care is needed [89].
There is also clearly a need for a simple screening instrument for assessing abuse of dementia
sufferers [29].
IV.2. OBJECTIVE
The objective of the present study is to examine the potential utility of a child abuse scale in
detecting maltreatment of institutionalized subjects with AD.
IV.3. MATERIALS AND METHODS
There were included in this study 88 subjects – 57 women and 31 men – with mild (FAST
stage 4; n=31), moderate (FAST stage 5; n=46) and moderately-severe (FAST stages 6a and
6b; n=11) AD. The participants in this study are living in six institutional settings from the
North-East region of Romania. The present study is based on the 38-item Child Abuse and
Trauma Scale (CATS), which was developed by Sanders and Becker-Lausen as a quantitative
measure that would reflect the frequency and extent of different types of abuse in childhood
and adolescence [142]. The factorial analysis on the CATS yielded three distinct subscales: a
6-item sexual abuse subscale, a 6-item punishment subscale and a 14-item neglect/negative
home atmosphere subscale. Responses to each item were scored on a five-point Likert scale (0
= never, 1 = rarely, 2 = sometimes, 3 = very often, 4 = always). Kent and Waller added a
fourth subscale comprised of 7 already existing items of CATS which reflect emotional abuse
[73]. In the present study, the items of the CAT scale have been adapted for use in the people
who live in institutional settings, taking into consideration the four subscales mentioned
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above. In addition, the adapted version of CATS has been extended by drawing from 5 items
of the initial instrument a new subscale reflecting physical abuse. The appraisal of semantic
equivalence consisted of two translations into Romanian and respective translations back to
English. The satisfactory Romanian version of the 38-item adapted CAT scale consisting of
the five subscales has been administered between June and August 2010 to institutionalized
people with different stages of AD, being presented to them as an assisted living environment
questionnaire. The study was performed with the written consent of the managers of the
institutional settings and the approval of the interviewed subjects. Both the managers and the
participants were assured of confidentiality. The statistical analysis has been performed using
the SPSS 15.0 program.
IV.4. RESULTS
The overall scale has a high internal consistency (Cronbach’s alpha = .975). Additionally,
reliability is good for each of the four initial subscales, as follows: for the sexual abuse
subscale, α = .854; for the punishment subscale, α = .853; for the neglect subscale, α = .964;
for the emotional abuse subscale, α = .952. The new subscale of physical abuse also has a
high level of internal consistency (alpha = .836). Most of the intercorrelations (Pearson’s r) of
the abuse subscales are strong, with the exception of the associations between the sexual
abuse subscale and the other subscales, which are moderate (see Table 4.1).
Table 4.1. Bivariate correlations (Pearson’s r) between the abuse subscales
By using repeated-measures ANOVA, the differences between the pairs of subscales proved
to be significant (p<0.001), suggesting that each subscale illustrates a particular dimension of
abuse. The mean values of the scores on the abuse subscales are very similar for five of the
institutional settings. Regarding the sixth institutional facility, the mean values of the scores
reported by the subjects are much reduced, suggesting better life conditions (see Fig. 4.3).
With respect to the frequency of occurrence, neglect and emotional abuse were the most
common forms of abuse reported by the study participants, followed by punishment and
physical abuse, while sexual abuse was the least reported.
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Fig. 4.3. Mean values of the scores reported on the abuse subscales for each of the six institutions
(scores for each item range from 0 (never) to 4 (always))
By applying independent samples t-test, the women questioned in this study have been found
to be more predisposed than men to sexual abuse (t(86) = 2.81, p<0.05), while the men have
been found to be more predisposed to physical abuse (t(86) = 2.06, p<0.05). The effects of the
AD stage on the abuse scale measures have been tested using one-way ANOVA, which
indicates statistically significant differences between the three stages of the disease for the
punishment (F (2, 85) = 4.64, p<0.05), neglect (F (2, 85) = 5.06, p<0.05) and emotional abuse
(F (2, 85) = 3.32, p<0.05) subscales. To precisely localize these differences, the Bonferroni
post hoc test was used, which demonstrates that the significant differences (p<0.05) appear
between the mild stage and the moderate stage of AD for three abuse subscales – punishment,
neglect and emotional abuse.
IV.5. DISCUSSION
The version of CATS used in this study appears to be a unified construct that reliably
measures the multidimensional nature of the abusive experiences lived by institutionalized
AD persons. Neglect and emotional (primarily verbal) abuse are most frequently reported in
the present study by the interviewed subjects. This observation is in agreement with other
studies indicating that neglect is the most common form of elder maltreatment [26, 80]. Other
studies have also found that verbal abuse is the most common form of mistreatment in
vulnerable people with dementia [29, 136]. Physical abuse is less reported in the current
study. This is consistent with another study that found few cases of physical abuse of people
with dementia living in the community [31]. In contrast, it was shown that physical abuse was
one of the most often reported forms of elder abuse [87]. Sexual abuse is the least common
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form of mistreatment reported by the participants in the present study. This finding adds
further support to previous evidence indicating that sexual abuse is the most underreported
type of elder maltreatment [26]. The present study also suggests that the subjects with mild
AD report lower levels of punishment, neglect and emotional abuse when compared to the
subjects in more advanced stages of the disease. The abuse screening instrument used here
does not mention who acts abusively – the professional caregivers, the residents or both – so
that the subjects would not be reluctant to report abuse. Awareness of risk factors and clinical
manifestations enables primary care physicians to provide early detection of elder abuse [80].
Moreover, previous studies have suggested that both older people and their carers should be
screened routinely for abuse [32, 89].
V. ETHICAL AND FORENSIC IMPLICATIONS OF RETROGENESIS
V.1. OBJECTIVE
The objective of the present study is to provide expert opinion on the possible ethical and
forensic implications of retrogenesis.
V.2. MATERIALS AND METHODS
This study was conducted in 2010 in Iași, Romania, and represents an expert opinion survey.
After the key themes were identified through literature review, a 6-item instrument was
constructed and named “Questionnaire regarding possible ethical and forensic implications of
retrogenesis”. The questionnaire was administered to 49 professionals who are directly
involved in both clinical and forensic evaluation of AD individuals, as follows: 20
psychiatrists and 17 psychologists from the “Socola” Clinical Hospital of Psychiatry Iași, and
12 forensic pathologists from the Institute of Forensic Medicine Iași. The items were scored
using a five-point Likert scale (1 = strongly disagree, 2 = disagree, 3 = not sure, 4 = agree, 5 =
strongly agree). The concept of retrogenesis was clearly described to the respondents before
answering the questions. The results were statistically analyzed using the SPSS 17.0 program.
V.3. RESULTS
By applying the Kruskal-Wallis test, the three professional groups included in this study have
been analyzed comparatively with respect to the responses to each of the six items of the
questionnaire. There were no statistically significant differences of opinion (p>0.05) between
psychiatrists, psychologists and forensic pathologists in the responses to the questions (see
Table 5.1).
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Table 5.1. Kruskal-Wallis test comparison of the mean ranks of the scores that correspond to the
three professional groups with regard to each of the six items of the questionnaire
The Chi square test was used to illustrate the general attitude of the respondents toward each
item, as follows: the majority of the survey respondents considered it ethical to start from the
concept of retrogenesis when approaching AD; most experts agreed that it would be ethical to
use psychometric tests and programs of cognitive stimulation originally developed for the
child in the person with AD; more than half of the professionals involved in this study
considered it ethical to apply child abuse evaluation tests to the AD persons; 61.2% of the
opinion survey respondents agreed that it would be necessary to use the concept of
retrogenesis for assessing mental capacity in these patients; and the majority of the
professionals surveyed herein pointed out that it would be necessary to enact legislative
proposals on the protection of the person with AD which would be adapted after the model of
the current child protection legislation.
V.4. DISCUSSION
The experts were asked if they consider it ethical to start from the concept of retrogenesis
when approaching AD. Most of the experts were found to have a positive attitude toward this
issue. However, great care must be exercised in approaching AD individuals, so that they
would not find it humiliating to be applied tests or to be involved in activities that have
initially been designed for children. Childhood intelligence test measures proved to be useful
in assessing cognition in the AD subjects [147]. In this regard, the survey participants have
been asked if they consider it ethical to apply the psychometric tests for the child to the person
with AD, and the majority of them showed their agreement with this approach. Additionally,
most of the experts questioned in this survey considered it ethical to use programs of
cognitive stimulation for the child in the AD person. Previous research suggested that
cognitive training has the potential to improve cognitive function in healthy older adults and
to slow decline in individuals with mild cognitive impairment or AD [49]. In the United
States, the legislation addressing domestic or institutional abuse of the elderly is based on the
laws addressing child abuse [3, 14]. The findings of the present study indicate that more than
half of the survey respondents consider it ethical to apply child abuse evaluation tests to the
person with AD. Moreover, a stage-specific retrogenic assessment of mental capacity should
be proposed, as 61.2% of the professionals involved in the present survey have agreed that it
would be necessary to use the concept of retrogenesis for assessing mental capacity in persons
with AD. Additionally, a British source has emphasized that there is no single piece of
legislation that covers child protection, but rather a myriad of laws and guidance that are
continually being amended, updated and revoked [93]. In contrast, an article written by
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Alzheimer Europe representatives has drawn attention to the fact that there is very little
legislation that would directly refer to the protection and rights of people with dementia [57].
The majority of experts involved in the present study noted that it would be necessary to enact
legislative proposals on the protection of the AD patient, which would be adapted after the
model of the child protection legislation.
VI. FINAL CONCLUSIONS & THESIS CONTRIBUTIONS
This doctoral thesis provides new ways of understanding AD in order to improve the
management of this very common disorder of later life.
The first significant contribution of the present thesis is to provide strong evidence for an
EEG retrogenic model showing that electrophysiologic changes in AD reverse the normal
developmental patterns. Such a retrogenic model could help us to improve the management
and the general understanding of AD.
Another major contribution of this thesis is to demonstrate that neuroanatomical brain
changes in AD mirror the ones in normal development. In this regard, it has been shown
that the cortical regions that normally mature last are the first to degenerate in AD. In
conjunction with this observation, it has been illustrated that the sequence of gray matter
(GM) decline in AD reverses the sequence of GM maturation. Thus, the present thesis
provides evidence for a brain structural/GM retrogenic model that could be relevant for a
better understanding of the nature of AD.
The finding that an instrument which would ordinarily be used to measure abuse in
childhood and adolescence can efficiently assess different types of abuse of
institutionalized AD subjects provides new evidence for the practical utility of the concept
of retrogenesis. In this regard, Child Abuse and Trauma Scale has been adapted for use in
the people who live in institutional settings and extended by drawing from within the
existing items a fifth subscale reflecting physical abuse. The results of this study will
hopefully contribute to the more widespread identification of abuse in persons with
dementia, as well as to the development of prevention and intervention strategies.
Another important contribution of this PhD thesis is to offer expert opinion on the possible
ethical and forensic implications of retrogenesis. In this regard, a six-item questionnaire
has been constructed and applied to three professional groups, namely, psychiatrists,
psychologists and forensic pathologists. Most professionals surveyed herein believe that
there are broad implications of the retrogenesis scientific findings from the perspective of
patient evaluation, need for activities, and the need for social protection. This appears to be
the first survey of opinion regarding the ethical and forensic implications of the
retrogenesis process in AD, and it should be extended to a larger geographical group of
experts, so that retrogenesis and its possible implications could be studied on a larger scale.
The final purpose would be to make the concept of retrogenesis to become both widely
accepted and practically useful in the management of AD individuals.
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