An ambitious study published in JAMA Dec 13 sought to answer the questions above, trying out whether mindfulness (an hour/day!), exercise (~45’/day) or both could help folks worried about their own brain functioning. Health education sessions were a control group. The short answer: nothing improved. But is there anything to glean from this work, which seems like a well-performed randomized controlled clinical trial?
Even though there were no improvements in the subjects’ cognitive measures or MRI brain measurements, these subjects, median age 71.2, did not have declining performance over 18 months either! These were not the same cognitive measures used in the recent lecanemab study or older donepezil studies, since these subjects had “subjective cognitve concerns.” In the drug studies, subjects presumably met objective criteria for at least “mild cognitive impairment (MCI),” but even those who received the drug declined over the same time frame, 18 months.
If nothing declined, does that mean that something worked even in the “attention control” group who got educational sessions? Well….
What are “subjective cognitive concerns,” “subjective cognitive impairments” or “subjective cognitive declines (SCD)”? As the names suggest, they are problems perceived by subjects themselves, but the subjects score in the “healthy” range on cognitive tests. These folks were worried enough to see a doctor; anxiety and depression are known to cause similar concerns (along with chemo or COVID “brain fog”).
It’s an arena with overlapping symptoms like forgetfulness, confusion, and allowing automatic software upgrades that make your phone or computer worse (just kidding on the last one, right?)
The CDC says SCD affects about 10% of Americans >age 45 (almost 12% > age 65), has called it a Public Health Issue and put it in their Healthy Brain Initiative (2018-2023). Yet SCD does not have a specific definition in references like DSM-5 or ICD-11 (the former does mention mild, i.e. not major neurocogntive disorders in a vague way, and the latter does have broad labels where it might fit).
The JAMA study used the screening test of Blessed Memory, for enrollment (so to speak, named after UK psychiatrist G. Blessed), and excluded subjects with lots of conditions, to have a cohort in good general health. During the study, they tested subjects with eight other measures. The lecanemab study used conventional batteries of dementia tests, including CDR-SB, ADAS-Cog14, etc.
Can a PCP easily screen for SCD or MCI? Well, no. The US Preventive Services Task Force reviewed nearly a thousand articles, many tests, data and treatment concepts; in 2020 they concluded “…There is no empiric evidence… that screening for cognitive impairment… improves patient, caregiver, family, or clinician decision making….”
Many therapies have failed most subjects with a diagnosis of MCI, mild Alzheimer’s Disease (AD) or established AD, so drug makers have long thought that if they could just get subjects even earlier, the outcomes might look better [in oncology we might call that the Will Rogers Phenomenon (NEJM), or lead-time / stage migration bias].
There are only a few studies of SCD’s “natural history” easily found, and its context within healthy populations. Knowing if the attention given to the JAMA study control group (health education) might have “worked” against further decline depends on being confident about understanding what happens to SCD folks over time with no interventions at all. Of course, maybe the JAMA study just confirms the null hypothesis.
A recent scoping review, a “trajectory study,” and a meta-analysis from dementia researchers seem to link SCD to AD or other dementias, as if it were a preliminary condition. The timeframe of worsening might anywhere from four to ten years or longer. However, Prof R. Howard had a cautionary short editorial comment about SCD in Lancet 2020, and what it might not be “good for.”
Three things AlzGadfly took away from the Lenze study in JAMA: 1) over the relatively short period of 18 months, most of these 70-somethings had no significant changes, better or worse, in brain function or brain MRI imaging, even though they worried about it, so maybe that’s good news;
2) even though the researchers screened >6K potential subjects and ended up with only 585, then split them four ways so each group was <153, these studies are feasible in a multi-institutional way, so let’s have more of them, even if it was seven years from enrollment to publication; and
3) if you like mindfulness and/or exercise, go for it, at least they won’t make things worse! In post-hoc analysis, some things in the exercise group actually got better with statistical significance (fitness, body mass, sleep Supplemental Online Content), but no cognitive measures improved.
Yes, the Agatha Christie detective Hercule Poirot liked to exercise his little grey cells…albeit quietly, with his eyes closed (meditating AND exercising?), perhaps thinking about “reverse causation”?!? Or should we jes’ fehgeddaboudid…and move on….again….
